Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study
Identifieur interne : 000217 ( Pmc/Corpus ); précédent : 000216; suivant : 000218Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study
Auteurs : Ha Poirel ; Ms Cairo ; Na Heerema ; J. Swansbury ; A. Aupérin ; E. Launay ; Wg Sanger ; P. Talley ; Sl Perkins ; M. Raphaël ; K. Mccarthy ; R. Sposto ; M. Gerrard ; A. Bernheim ; C. PatteSource :
- Leukemia [ 0887-6924 ] ; 2008.
Abstract
Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event free survival (EFS) in pediatric mature B-NHL treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt Lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature-B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24 associated chromosomal aberrations were +1q [29%], +7q and del(13q) [14% each]. The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 [34%] was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS [HR: 6.1 (p=0.030), 2.5 (p=0.015), 4.0 (p=0.0003), respectively]. The adverse prognosis of R8q24 was observed only in DLBCL while del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk adapted therapy in childhood mature-B-NHL.
Url:
DOI: 10.1038/leu.2008.312
PubMed: 19020548
PubMed Central: 2988438
Links to Exploration step
PMC:2988438Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study</title><author><name sortKey="Poirel, Ha" sort="Poirel, Ha" uniqKey="Poirel H" first="Ha" last="Poirel">Ha Poirel</name><affiliation><nlm:aff id="A1">Biological Hematology, CHU Avicenne – Université Paris 13, Bobigny, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Cliniques Universitaire Saint-Luc UCL & de Duve Institute, Hematological Genetics & Human Molecular Genetics (GEHU), Brussels, Belgium</nlm:aff></affiliation></author><author><name sortKey="Cairo, Ms" sort="Cairo, Ms" uniqKey="Cairo M" first="Ms" last="Cairo">Ms Cairo</name><affiliation><nlm:aff id="A3">Division of Pediatric Blood and Marrow Transplantation, Morgan Stanley Children’s Hospital of New York Presbyterian, Columbia University, New York, NY-USA</nlm:aff></affiliation></author><author><name sortKey="Heerema, Na" sort="Heerema, Na" uniqKey="Heerema N" first="Na" last="Heerema">Na Heerema</name><affiliation><nlm:aff id="A4">Department of Pathology - Cytogenetics, The Ohio State University, Columbus, OH-USA</nlm:aff></affiliation></author><author><name sortKey="Swansbury, J" sort="Swansbury, J" uniqKey="Swansbury J" first="J" last="Swansbury">J. Swansbury</name><affiliation><nlm:aff id="A5">Haematology Cytogenetics, The Royal Marsden Hospital, Sutton, UK</nlm:aff></affiliation></author><author><name sortKey="Auperin, A" sort="Auperin, A" uniqKey="Auperin A" first="A" last="Aupérin">A. Aupérin</name><affiliation><nlm:aff id="A6">Department of Biostatistics, Institut Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="Launay, E" sort="Launay, E" uniqKey="Launay E" first="E" last="Launay">E. Launay</name><affiliation><nlm:aff id="A1">Biological Hematology, CHU Avicenne – Université Paris 13, Bobigny, France</nlm:aff></affiliation></author><author><name sortKey="Sanger, Wg" sort="Sanger, Wg" uniqKey="Sanger W" first="Wg" last="Sanger">Wg Sanger</name><affiliation><nlm:aff id="A7">Human Genetics Laboratory, University of Nebraska Medical Center, Omaha, NE-USA</nlm:aff></affiliation></author><author><name sortKey="Talley, P" sort="Talley, P" uniqKey="Talley P" first="P" last="Talley">P. Talley</name><affiliation><nlm:aff id="A8">Cytogenetics, Sheffield Children’s Hospital, Sheffield, UK</nlm:aff></affiliation></author><author><name sortKey="Perkins, Sl" sort="Perkins, Sl" uniqKey="Perkins S" first="Sl" last="Perkins">Sl Perkins</name><affiliation><nlm:aff id="A9">Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA</nlm:aff></affiliation></author><author><name sortKey="Raphael, M" sort="Raphael, M" uniqKey="Raphael M" first="M" last="Raphaël">M. Raphaël</name><affiliation><nlm:aff id="A1">Biological Hematology, CHU Avicenne – Université Paris 13, Bobigny, France</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Biological Hematology, CHU Bicêtre –Assistance Publique-Hôpitaux de Paris, INSERM U802, Université Paris-Sud 11, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Mccarthy, K" sort="Mccarthy, K" uniqKey="Mccarthy K" first="K" last="Mccarthy">K. Mccarthy</name><affiliation><nlm:aff id="A11">Department of Pathology, Gloucestershire Hospitals, NHS Foundation, Gloucestershire, UK</nlm:aff></affiliation></author><author><name sortKey="Sposto, R" sort="Sposto, R" uniqKey="Sposto R" first="R" last="Sposto">R. Sposto</name><affiliation><nlm:aff id="A12">Department of Biostatistics, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA-USA</nlm:aff></affiliation></author><author><name sortKey="Gerrard, M" sort="Gerrard, M" uniqKey="Gerrard M" first="M" last="Gerrard">M. Gerrard</name><affiliation><nlm:aff id="A13">Department of Paediatric Oncology, Sheffield Children’s Hospital, Sheffield, UK</nlm:aff></affiliation></author><author><name sortKey="Bernheim, A" sort="Bernheim, A" uniqKey="Bernheim A" first="A" last="Bernheim">A. Bernheim</name><affiliation><nlm:aff id="A14">Laboratoire de genomique cellulaire des cancers, Institut Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="Patte, C" sort="Patte, C" uniqKey="Patte C" first="C" last="Patte">C. Patte</name><affiliation><nlm:aff id="A15">Department of Pediatric onco-hematology, Institut Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19020548</idno><idno type="pmc">2988438</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988438</idno><idno type="RBID">PMC:2988438</idno><idno type="doi">10.1038/leu.2008.312</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000217</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000217</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study</title><author><name sortKey="Poirel, Ha" sort="Poirel, Ha" uniqKey="Poirel H" first="Ha" last="Poirel">Ha Poirel</name><affiliation><nlm:aff id="A1">Biological Hematology, CHU Avicenne – Université Paris 13, Bobigny, France</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Cliniques Universitaire Saint-Luc UCL & de Duve Institute, Hematological Genetics & Human Molecular Genetics (GEHU), Brussels, Belgium</nlm:aff></affiliation></author><author><name sortKey="Cairo, Ms" sort="Cairo, Ms" uniqKey="Cairo M" first="Ms" last="Cairo">Ms Cairo</name><affiliation><nlm:aff id="A3">Division of Pediatric Blood and Marrow Transplantation, Morgan Stanley Children’s Hospital of New York Presbyterian, Columbia University, New York, NY-USA</nlm:aff></affiliation></author><author><name sortKey="Heerema, Na" sort="Heerema, Na" uniqKey="Heerema N" first="Na" last="Heerema">Na Heerema</name><affiliation><nlm:aff id="A4">Department of Pathology - Cytogenetics, The Ohio State University, Columbus, OH-USA</nlm:aff></affiliation></author><author><name sortKey="Swansbury, J" sort="Swansbury, J" uniqKey="Swansbury J" first="J" last="Swansbury">J. Swansbury</name><affiliation><nlm:aff id="A5">Haematology Cytogenetics, The Royal Marsden Hospital, Sutton, UK</nlm:aff></affiliation></author><author><name sortKey="Auperin, A" sort="Auperin, A" uniqKey="Auperin A" first="A" last="Aupérin">A. Aupérin</name><affiliation><nlm:aff id="A6">Department of Biostatistics, Institut Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="Launay, E" sort="Launay, E" uniqKey="Launay E" first="E" last="Launay">E. Launay</name><affiliation><nlm:aff id="A1">Biological Hematology, CHU Avicenne – Université Paris 13, Bobigny, France</nlm:aff></affiliation></author><author><name sortKey="Sanger, Wg" sort="Sanger, Wg" uniqKey="Sanger W" first="Wg" last="Sanger">Wg Sanger</name><affiliation><nlm:aff id="A7">Human Genetics Laboratory, University of Nebraska Medical Center, Omaha, NE-USA</nlm:aff></affiliation></author><author><name sortKey="Talley, P" sort="Talley, P" uniqKey="Talley P" first="P" last="Talley">P. Talley</name><affiliation><nlm:aff id="A8">Cytogenetics, Sheffield Children’s Hospital, Sheffield, UK</nlm:aff></affiliation></author><author><name sortKey="Perkins, Sl" sort="Perkins, Sl" uniqKey="Perkins S" first="Sl" last="Perkins">Sl Perkins</name><affiliation><nlm:aff id="A9">Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA</nlm:aff></affiliation></author><author><name sortKey="Raphael, M" sort="Raphael, M" uniqKey="Raphael M" first="M" last="Raphaël">M. Raphaël</name><affiliation><nlm:aff id="A1">Biological Hematology, CHU Avicenne – Université Paris 13, Bobigny, France</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Biological Hematology, CHU Bicêtre –Assistance Publique-Hôpitaux de Paris, INSERM U802, Université Paris-Sud 11, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Mccarthy, K" sort="Mccarthy, K" uniqKey="Mccarthy K" first="K" last="Mccarthy">K. Mccarthy</name><affiliation><nlm:aff id="A11">Department of Pathology, Gloucestershire Hospitals, NHS Foundation, Gloucestershire, UK</nlm:aff></affiliation></author><author><name sortKey="Sposto, R" sort="Sposto, R" uniqKey="Sposto R" first="R" last="Sposto">R. Sposto</name><affiliation><nlm:aff id="A12">Department of Biostatistics, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA-USA</nlm:aff></affiliation></author><author><name sortKey="Gerrard, M" sort="Gerrard, M" uniqKey="Gerrard M" first="M" last="Gerrard">M. Gerrard</name><affiliation><nlm:aff id="A13">Department of Paediatric Oncology, Sheffield Children’s Hospital, Sheffield, UK</nlm:aff></affiliation></author><author><name sortKey="Bernheim, A" sort="Bernheim, A" uniqKey="Bernheim A" first="A" last="Bernheim">A. Bernheim</name><affiliation><nlm:aff id="A14">Laboratoire de genomique cellulaire des cancers, Institut Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author><author><name sortKey="Patte, C" sort="Patte, C" uniqKey="Patte C" first="C" last="Patte">C. Patte</name><affiliation><nlm:aff id="A15">Department of Pediatric onco-hematology, Institut Gustave Roussy, Villejuif, France</nlm:aff></affiliation></author></analytic><series><title level="j">Leukemia</title><idno type="ISSN">0887-6924</idno><idno type="eISSN">1476-5551</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event free survival (EFS) in pediatric mature B-NHL treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt Lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature-B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24 associated chromosomal aberrations were +1q [29%], +7q and del(13q) [14% each]. The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 [34%] was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS [HR: 6.1 (p=0.030), 2.5 (p=0.015), 4.0 (p=0.0003), respectively]. The adverse prognosis of R8q24 was observed only in DLBCL while del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk adapted therapy in childhood mature-B-NHL.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Patte, C" uniqKey="Patte C">C Patte</name></author><author><name sortKey="Auperin, A" uniqKey="Auperin A">A Auperin</name></author><author><name sortKey="Gerrard, M" uniqKey="Gerrard M">M Gerrard</name></author><author><name sortKey="Michon, J" uniqKey="Michon J">J Michon</name></author><author><name sortKey="Pinkerson, Cr" uniqKey="Pinkerson C">CR Pinkerson</name></author><author><name sortKey="Sposto, R" uniqKey="Sposto R">R Sposto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cairo, Ms" uniqKey="Cairo M">MS Cairo</name></author><author><name sortKey="Gerrard, M" uniqKey="Gerrard M">M Gerrard</name></author><author><name sortKey="Sposto, R" uniqKey="Sposto R">R Sposto</name></author><author><name sortKey="Auperin, A" uniqKey="Auperin A">A Auperin</name></author><author><name sortKey="Pinkerson, Cr" uniqKey="Pinkerson C">CR Pinkerson</name></author><author><name sortKey="Michon, J" uniqKey="Michon J">J Michon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerrard, M" uniqKey="Gerrard M">M Gerrard</name></author><author><name sortKey="Cairo, Ms" uniqKey="Cairo M">MS Cairo</name></author><author><name sortKey="Weston, C" uniqKey="Weston C">C Weston</name></author><author><name sortKey="Auperin, A" uniqKey="Auperin A">A Auperin</name></author><author><name sortKey="Pinkerton, R" uniqKey="Pinkerton R">R Pinkerton</name></author><author><name sortKey="Lambilliote, A" uniqKey="Lambilliote A">A Lambilliote</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harris, Nl" uniqKey="Harris N">NL Harris</name></author><author><name sortKey="Jaffe, Es" uniqKey="Jaffe E">ES Jaffe</name></author><author><name sortKey="Stein, H" uniqKey="Stein H">H Stein</name></author><author><name sortKey="Banks, Pm" uniqKey="Banks P">PM Banks</name></author><author><name sortKey="Chan, Jk" uniqKey="Chan J">JK Chan</name></author><author><name sortKey="Cleary, Ml" uniqKey="Cleary M">ML Cleary</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jaffe, Es" uniqKey="Jaffe E">ES Jaffe</name></author><author><name sortKey="Harris, Nl" uniqKey="Harris N">NL Harris</name></author><author><name sortKey="Stein, H" uniqKey="Stein H">H Stein</name></author><author><name sortKey="Vardiman, Jw" uniqKey="Vardiman J">JW Vardiman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lenoir, Gm" uniqKey="Lenoir G">GM Lenoir</name></author><author><name sortKey="Preud Omme, Jl" uniqKey="Preud Omme J">JL Preud’homme</name></author><author><name sortKey="Bernheim, A" uniqKey="Bernheim A">A Bernheim</name></author><author><name sortKey="Berger, R" uniqKey="Berger R">R Berger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Battey, J" uniqKey="Battey J">J Battey</name></author><author><name sortKey="Moulding, C" uniqKey="Moulding C">C Moulding</name></author><author><name sortKey="Taub, R" uniqKey="Taub R">R Taub</name></author><author><name sortKey="Murphy, W" uniqKey="Murphy W">W Murphy</name></author><author><name sortKey="Stewart, T" uniqKey="Stewart T">T Stewart</name></author><author><name sortKey="Potter, H" uniqKey="Potter H">H Potter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zech, L" uniqKey="Zech L">L Zech</name></author><author><name sortKey="Haglund, U" uniqKey="Haglund U">U Haglund</name></author><author><name sortKey="Nilsson, K" uniqKey="Nilsson K">K Nilsson</name></author><author><name sortKey="Klein, G" uniqKey="Klein G">G Klein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bernheim, A" uniqKey="Bernheim A">A Bernheim</name></author><author><name sortKey="Berger, R" uniqKey="Berger R">R Berger</name></author><author><name sortKey="Lenoir, G" uniqKey="Lenoir G">G Lenoir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blum, Ka" uniqKey="Blum K">KA Blum</name></author><author><name sortKey="Lozanski, G" uniqKey="Lozanski G">G Lozanski</name></author><author><name sortKey="Byrd, Jc" uniqKey="Byrd J">JC Byrd</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilda, M" uniqKey="Wilda M">M Wilda</name></author><author><name sortKey="Bruch, J" uniqKey="Bruch J">J Bruch</name></author><author><name sortKey="Harder, L" uniqKey="Harder L">L Harder</name></author><author><name sortKey="Rawer, D" uniqKey="Rawer D">D Rawer</name></author><author><name sortKey="Reiter, A" uniqKey="Reiter A">A Reiter</name></author><author><name sortKey="Borkhardt, A" uniqKey="Borkhardt A">A Borkhardt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lindstrom, Ms" uniqKey="Lindstrom M">MS Lindstrom</name></author><author><name sortKey="Wiman, Kg" uniqKey="Wiman K">KG Wiman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berger, R" uniqKey="Berger R">R Berger</name></author><author><name sortKey="Bernheim, A" uniqKey="Bernheim A">A Bernheim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berger, R" uniqKey="Berger R">R Berger</name></author><author><name sortKey="Le Coniat, M" uniqKey="Le Coniat M">M Le Coniat</name></author><author><name sortKey="Derre, J" uniqKey="Derre J">J Derre</name></author><author><name sortKey="Vecchione, D" uniqKey="Vecchione D">D Vecchione</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Jl" uniqKey="Lai J">JL Lai</name></author><author><name sortKey="Fenaux, P" uniqKey="Fenaux P">P Fenaux</name></author><author><name sortKey="Zandecki, M" uniqKey="Zandecki M">M Zandecki</name></author><author><name sortKey="Nelken, B" uniqKey="Nelken B">B Nelken</name></author><author><name sortKey="Huart, Jj" uniqKey="Huart J">JJ Huart</name></author><author><name sortKey="Deminatti, M" uniqKey="Deminatti M">M Deminatti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kornblau, Sm" uniqKey="Kornblau S">SM Kornblau</name></author><author><name sortKey="Goodacre, A" uniqKey="Goodacre A">A Goodacre</name></author><author><name sortKey="Cabanillas, F" uniqKey="Cabanillas F">F Cabanillas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johansson, B" uniqKey="Johansson B">B Johansson</name></author><author><name sortKey="Mertens, F" uniqKey="Mertens F">F Mertens</name></author><author><name sortKey="Mitelman, F" uniqKey="Mitelman F">F Mitelman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berger, R" uniqKey="Berger R">R Berger</name></author><author><name sortKey="Bernheim, A" uniqKey="Bernheim A">A Bernheim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knutsen, T" uniqKey="Knutsen T">T Knutsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garcia, Jl" uniqKey="Garcia J">JL Garcia</name></author><author><name sortKey="Hernandez, Jm" uniqKey="Hernandez J">JM Hernandez</name></author><author><name sortKey="Gutierrez, Nc" uniqKey="Gutierrez N">NC Gutierrez</name></author><author><name sortKey="Flores, T" uniqKey="Flores T">T Flores</name></author><author><name sortKey="Gonzalez, D" uniqKey="Gonzalez D">D Gonzalez</name></author><author><name sortKey="Calasanz, Mj" uniqKey="Calasanz M">MJ Calasanz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lones, Ma" uniqKey="Lones M">MA Lones</name></author><author><name sortKey="Sanger, Wg" uniqKey="Sanger W">WG Sanger</name></author><author><name sortKey="Le Beau, Mm" uniqKey="Le Beau M">MM Le Beau</name></author><author><name sortKey="Heerema, Na" uniqKey="Heerema N">NA Heerema</name></author><author><name sortKey="Sposto, R" uniqKey="Sposto R">R Sposto</name></author><author><name sortKey="Perkins, Sl" uniqKey="Perkins S">SL Perkins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heerema, Na" uniqKey="Heerema N">NA Heerema</name></author><author><name sortKey="Bernheim, A" uniqKey="Bernheim A">A Bernheim</name></author><author><name sortKey="Lim, Ms" uniqKey="Lim M">MS Lim</name></author><author><name sortKey="Look, At" uniqKey="Look A">AT Look</name></author><author><name sortKey="Pasqualucci, L" uniqKey="Pasqualucci L">L Pasqualucci</name></author><author><name sortKey="Raetz, E" uniqKey="Raetz E">E Raetz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dave, Bj" uniqKey="Dave B">BJ Dave</name></author><author><name sortKey="Weisenburger, Dd" uniqKey="Weisenburger D">DD Weisenburger</name></author><author><name sortKey="Higgins, Cm" uniqKey="Higgins C">CM Higgins</name></author><author><name sortKey="Pickering, Dl" uniqKey="Pickering D">DL Pickering</name></author><author><name sortKey="Hess, Mm" uniqKey="Hess M">MM Hess</name></author><author><name sortKey="Chan, Wc" uniqKey="Chan W">WC Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patte, C" uniqKey="Patte C">C Patte</name></author><author><name sortKey="Auperin, A" uniqKey="Auperin A">A Auperin</name></author><author><name sortKey="Michon, J" uniqKey="Michon J">J Michon</name></author><author><name sortKey="Behrendt, H" uniqKey="Behrendt H">H Behrendt</name></author><author><name sortKey="Leverger, G" uniqKey="Leverger G">G Leverger</name></author><author><name sortKey="Frappaz, D" uniqKey="Frappaz D">D Frappaz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lones, Ma" uniqKey="Lones M">MA Lones</name></author><author><name sortKey="Auperin, A" uniqKey="Auperin A">A Auperin</name></author><author><name sortKey="Raphael, M" uniqKey="Raphael M">M Raphael</name></author><author><name sortKey="Mccarthy, K" uniqKey="Mccarthy K">K McCarthy</name></author><author><name sortKey="Perkins, Sl" uniqKey="Perkins S">SL Perkins</name></author><author><name sortKey="Maclennan, Ka" uniqKey="Maclennan K">KA MacLennan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaffer, Lg" uniqKey="Shaffer L">LG Shaffer</name></author><author><name sortKey="Tommerup, N" uniqKey="Tommerup N">N Tommerup</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reiter, A" uniqKey="Reiter A">A Reiter</name></author><author><name sortKey="Schrappe, M" uniqKey="Schrappe M">M Schrappe</name></author><author><name sortKey="Tiemann, M" uniqKey="Tiemann M">M Tiemann</name></author><author><name sortKey="Ludwig, Wd" uniqKey="Ludwig W">WD Ludwig</name></author><author><name sortKey="Yakisan, E" uniqKey="Yakisan E">E Yakisan</name></author><author><name sortKey="Zimmermann, M" uniqKey="Zimmermann M">M Zimmermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barin, C" uniqKey="Barin C">C Barin</name></author><author><name sortKey="Valtat, C" uniqKey="Valtat C">C Valtat</name></author><author><name sortKey="Briault, S" uniqKey="Briault S">S Briault</name></author><author><name sortKey="Bremont, Jl" uniqKey="Bremont J">JL Bremont</name></author><author><name sortKey="Petit, A" uniqKey="Petit A">A Petit</name></author><author><name sortKey="Lejars, O" uniqKey="Lejars O">O Lejars</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ogden, Ca" uniqKey="Ogden C">CA Ogden</name></author><author><name sortKey="Pound, Jd" uniqKey="Pound J">JD Pound</name></author><author><name sortKey="Batth, Bk" uniqKey="Batth B">BK Batth</name></author><author><name sortKey="Owens, S" uniqKey="Owens S">S Owens</name></author><author><name sortKey="Johannessen, I" uniqKey="Johannessen I">I Johannessen</name></author><author><name sortKey="Wood, K" uniqKey="Wood K">K Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Calin, Ga" uniqKey="Calin G">GA Calin</name></author><author><name sortKey="Liu, Cg" uniqKey="Liu C">CG Liu</name></author><author><name sortKey="Sevignani, C" uniqKey="Sevignani C">C Sevignani</name></author><author><name sortKey="Ferracin, M" uniqKey="Ferracin M">M Ferracin</name></author><author><name sortKey="Felli, N" uniqKey="Felli N">N Felli</name></author><author><name sortKey="Dumitru, Cd" uniqKey="Dumitru C">CD Dumitru</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hummel, M" uniqKey="Hummel M">M Hummel</name></author><author><name sortKey="Bentink, S" uniqKey="Bentink S">S Bentink</name></author><author><name sortKey="Berger, H" uniqKey="Berger H">H Berger</name></author><author><name sortKey="Klapper, W" uniqKey="Klapper W">W Klapper</name></author><author><name sortKey="Wessendorf, S" uniqKey="Wessendorf S">S Wessendorf</name></author><author><name sortKey="Barth, Tf" uniqKey="Barth T">TF Barth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dave, Ss" uniqKey="Dave S">SS Dave</name></author><author><name sortKey="Fu, K" uniqKey="Fu K">K Fu</name></author><author><name sortKey="Wright, Gw" uniqKey="Wright G">GW Wright</name></author><author><name sortKey="Lam, Lt" uniqKey="Lam L">LT Lam</name></author><author><name sortKey="Kluin, P" uniqKey="Kluin P">P Kluin</name></author><author><name sortKey="Boerma, Ej" uniqKey="Boerma E">EJ Boerma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawasaki, C" uniqKey="Kawasaki C">C Kawasaki</name></author><author><name sortKey="Ohshim, K" uniqKey="Ohshim K">K Ohshim</name></author><author><name sortKey="Suzumiya, J" uniqKey="Suzumiya J">J Suzumiya</name></author><author><name sortKey="Kanda, M" uniqKey="Kanda M">M Kanda</name></author><author><name sortKey="Tsuchiya, T" uniqKey="Tsuchiya T">T Tsuchiya</name></author><author><name sortKey="Tamura, K" uniqKey="Tamura K">K Tamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akasaka, T" uniqKey="Akasaka T">T Akasaka</name></author><author><name sortKey="Akasaka, H" uniqKey="Akasaka H">H Akasaka</name></author><author><name sortKey="Ueda, C" uniqKey="Ueda C">C Ueda</name></author><author><name sortKey="Kanda, M" uniqKey="Kanda M">M Kanda</name></author><author><name sortKey="Tsuchiya, T" uniqKey="Tsuchiya T">T Tsuchiya</name></author><author><name sortKey="Tamura, K" uniqKey="Tamura K">K Tamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miles, R" uniqKey="Miles R">R Miles</name></author><author><name sortKey="Raphael, M" uniqKey="Raphael M">M Raphael</name></author><author><name sortKey="Mccarthy, K" uniqKey="Mccarthy K">K McCarthy</name></author><author><name sortKey="Wotherspoon, A" uniqKey="Wotherspoon A">A Wotherspoon</name></author><author><name sortKey="Lones, M" uniqKey="Lones M">M Lones</name></author><author><name sortKey="Cairo, M" uniqKey="Cairo M">M Cairo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oschlies, I" uniqKey="Oschlies I">I Oschlies</name></author><author><name sortKey="Klapper, W" uniqKey="Klapper W">W Klapper</name></author><author><name sortKey="Zimmermann, M" uniqKey="Zimmermann M">M Zimmermann</name></author><author><name sortKey="Krams, M" uniqKey="Krams M">M Krams</name></author><author><name sortKey="Wacker, Hh" uniqKey="Wacker H">HH Wacker</name></author><author><name sortKey="Burkhardt, B" uniqKey="Burkhardt B">B Burkhardt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rosenwald, A" uniqKey="Rosenwald A">A Rosenwald</name></author><author><name sortKey="Wright, G" uniqKey="Wright G">G Wright</name></author><author><name sortKey="Chan, Wc" uniqKey="Chan W">WC Chan</name></author><author><name sortKey="Connors, Jm" uniqKey="Connors J">JM Connors</name></author><author><name sortKey="Campo, E" uniqKey="Campo E">E Campo</name></author><author><name sortKey="Fisher, Ri" uniqKey="Fisher R">RI Fisher</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8704895</journal-id><journal-id journal-id-type="pubmed-jr-id">5536</journal-id><journal-id journal-id-type="nlm-ta">Leukemia</journal-id><journal-id journal-id-type="iso-abbrev">Leukemia</journal-id><journal-title-group><journal-title>Leukemia</journal-title></journal-title-group><issn pub-type="ppub">0887-6924</issn><issn pub-type="epub">1476-5551</issn></journal-meta><article-meta><article-id pub-id-type="pmid">19020548</article-id><article-id pub-id-type="pmc">2988438</article-id><article-id pub-id-type="doi">10.1038/leu.2008.312</article-id><article-id pub-id-type="manuscript">NIHMS107551</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Poirel</surname><given-names>HA</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref rid="FN2" ref-type="author-notes">17</xref></contrib><contrib contrib-type="author"><name><surname>Cairo</surname><given-names>MS</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref rid="FN2" ref-type="author-notes">17</xref></contrib><contrib contrib-type="author"><name><surname>Heerema</surname><given-names>NA</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Swansbury</surname><given-names>J</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Aupérin</surname><given-names>A</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Launay</surname><given-names>E</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sanger</surname><given-names>WG</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Talley</surname><given-names>P</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Perkins</surname><given-names>SL</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Raphaël</surname><given-names>M</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>McCarthy</surname><given-names>K</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Sposto</surname><given-names>R</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Gerrard</surname><given-names>M</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Bernheim</surname><given-names>A</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Patte</surname><given-names>C</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><on-behalf-of>FAB LMB 96 International Study Committee</on-behalf-of><xref ref-type="aff" rid="A16">16</xref></contrib-group><aff id="A1"><label>1</label>Biological Hematology, CHU Avicenne – Université Paris 13, Bobigny, France</aff><aff id="A2"><label>2</label>Cliniques Universitaire Saint-Luc UCL & de Duve Institute, Hematological Genetics & Human Molecular Genetics (GEHU), Brussels, Belgium</aff><aff id="A3"><label>3</label>Division of Pediatric Blood and Marrow Transplantation, Morgan Stanley Children’s Hospital of New York Presbyterian, Columbia University, New York, NY-USA</aff><aff id="A4"><label>4</label>Department of Pathology - Cytogenetics, The Ohio State University, Columbus, OH-USA</aff><aff id="A5"><label>5</label>Haematology Cytogenetics, The Royal Marsden Hospital, Sutton, UK</aff><aff id="A6"><label>6</label>Department of Biostatistics, Institut Gustave Roussy, Villejuif, France</aff><aff id="A7"><label>7</label>Human Genetics Laboratory, University of Nebraska Medical Center, Omaha, NE-USA</aff><aff id="A8"><label>8</label>Cytogenetics, Sheffield Children’s Hospital, Sheffield, UK</aff><aff id="A9"><label>9</label>Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA</aff><aff id="A10"><label>10</label>Biological Hematology, CHU Bicêtre –Assistance Publique-Hôpitaux de Paris, INSERM U802, Université Paris-Sud 11, Le Kremlin-Bicêtre, France</aff><aff id="A11"><label>11</label>Department of Pathology, Gloucestershire Hospitals, NHS Foundation, Gloucestershire, UK</aff><aff id="A12"><label>12</label>Department of Biostatistics, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA-USA</aff><aff id="A13"><label>13</label>Department of Paediatric Oncology, Sheffield Children’s Hospital, Sheffield, UK</aff><aff id="A14"><label>14</label>Laboratoire de genomique cellulaire des cancers, Institut Gustave Roussy, Villejuif, France</aff><aff id="A15"><label>15</label>Department of Pediatric onco-hematology, Institut Gustave Roussy, Villejuif, France</aff><aff id="A16"><label>16</label>Children’s Oncology Group (COG), Arcadia, CA, USA, Société Française d’Oncologie Pédiatrique (SFOP), France, and the United Kingdom Children’s Cancer Study Group (UKCCSG), Leicester, UK</aff><author-notes><corresp id="FN1">Correspondence Pr Hélène A Poirel, MD PhD, c/o Société Française des Cancers de l’enfant, <email>helene.antoine-poirel@uclouvain.be</email>, Hematological Genetics & Human Molecular Genetics (GEHU), Cliniques Universitaire Saint-Luc UCL & de Duve Institute, avenue Mounier, F, B-1200 Brussels - Belgium, Ph : +32 2 764 67 81, Fax: +32 2 764 69 36 <bold>and/or</bold> Pr Mitchell S. Cairo, MD, c/o <underline>Children’s</underline> Oncology Group Operations Office, <email>mc1310@columbia.edu</email>, Chief, Division of Pediatric Blood and Marrow Transplantation, Columbia University Medical Center, Morgan Stanley Children’s Hospital of New York Presbyterian, Columbia University, New York, NY-USA, Ph : +1 212 305 8316, Fax : +1 212 305 8428</corresp><fn id="FN2" fn-type="other"><label>17</label><p>should be considered co-primary first authors.</p></fn><fn id="FN3" fn-type="other"><p>A complete list of the participants in the cytogenetics study of the FAB/LMB96 International trial appears in the “Appendix”.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>28</day><month>10</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>20</day><month>11</month><year>2008</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2009</year></pub-date><pub-date pub-type="pmc-release"><day>19</day><month>11</month><year>2010</year></pub-date><volume>23</volume><issue>2</issue><fpage>323</fpage><lpage>331</lpage><pmc-comment>elocation-id from pubmed: 10.1038/leu.2008.312</pmc-comment>
<permissions><license xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms"><license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><p id="P1">Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event free survival (EFS) in pediatric mature B-NHL treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt Lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature-B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24 associated chromosomal aberrations were +1q [29%], +7q and del(13q) [14% each]. The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 [34%] was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS [HR: 6.1 (p=0.030), 2.5 (p=0.015), 4.0 (p=0.0003), respectively]. The adverse prognosis of R8q24 was observed only in DLBCL while del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk adapted therapy in childhood mature-B-NHL.</p></abstract><kwd-group><kwd>Childhood mature B-cell lymphoma</kwd><kwd>Burkitt lymphoma</kwd><kwd>DLBCL</kwd><kwd>cytogenetics</kwd><kwd>prognosis</kwd></kwd-group></article-meta></front><body><sec sec-type="intro" id="S1"><title>Introduction</title><p id="P2">We recently reported the clinical results of the first international randomized study in children and adolescents with mature B-cell lymphoma (FAB/LMB 96) <xref rid="R1" ref-type="bibr">1</xref>-<xref rid="R3" ref-type="bibr">3</xref>. In children with intermediate risk B-NHL, the 4 year event-free survival (EFS) and overall survival (OS) were 90.2% and 92.7%, respectively<xref rid="R1" ref-type="bibr">1</xref>. Low stage presentation (non resected stage I/II), normal LDH (< 2 times institutional upper limit) and response to COP (cyclophosphamide, vincristine and prednisone) reduction therapy greater then 20% were associated with higher EFS<xref rid="R1" ref-type="bibr">1</xref>. In patients with advanced B-NHL (bone marrow involvement ≥ 25% blasts [B-ALL] ± central nervous system involvement), the 4 year EFS and OS were 79 ± 3% and 82 ± 3%, respectively<xref rid="R2" ref-type="bibr">2</xref>. Poor response to COP (cyclophosphamide, vincristine, prednisone) reduction therapy and combined bone marrow and CNS disease were associated with a significantly poorer EFS<xref rid="R1" ref-type="bibr">1</xref>. In the low risk patients, with resected localized B-NHL, 4 year EFS and OS of 98.3 % and 99.2 3%, respectively, were obtained with a low intensity treatment without intrathecal chemotherapy<xref rid="R3" ref-type="bibr">3</xref>.</p><p id="P3">However, little information is available regarding the prognostic value of cytogenetic aberrations in childhood B-NHL, especially in those children treated on a uniform protocol. Mature B-cell lymphoma/leukemia in children are mainly represented by Burkitt lymphoma/leukemia (BL) and to a lesser extent by high grade B-cell (Burkitt-like or atypical Burkitt) lymphoma (BLL) and diffuse large B-cell lymphoma (DLBCL)<xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R5" ref-type="bibr">5</xref>. BL is a pathological entity characterized by chromosomal translocations associating the <italic>MYC</italic> gene (located at 8q24) to one of three immunoglobulin loci<xref rid="R6" ref-type="bibr">6</xref>-<xref rid="R9" ref-type="bibr">9</xref>. These cytogenetic translocations result in deregulated <italic>MYC</italic> expression, a well known oncogene responsible for maintaining the balance of cellular proliferation, differentiation, adhesion and apoptosis<xref rid="R10" ref-type="bibr">10</xref>. Other genetic changes, such as disruption of the p14ARF-MDM2-p53 pathway, have been identified in more than half of childhood sporadic BL and may provide further growth stimulation and apoptosis protection<xref rid="R11" ref-type="bibr">11</xref>,<xref rid="R12" ref-type="bibr">12</xref>. Some additional chromosomal alterations have been previously described, such as gains of the long arm of chromosomes 1 (+1q) or 7 (+7q) or 12 (+12q), deletion (del)17p13 and abnormalities of band 13q34, usually in adult BL, without or in the setting of an HIV infection<xref rid="R13" ref-type="bibr">13</xref>-<xref rid="R18" ref-type="bibr">18</xref>. Secondary abnormalities are said to be associated with tumor progression<xref rid="R19" ref-type="bibr">19</xref>, but their prognostic value has not been clearly evaluated and few cytogenetic data are available in pediatric BL<xref rid="R20" ref-type="bibr">20</xref>-<xref rid="R22" ref-type="bibr">22</xref>.</p><p id="P4">DLBCL is less common in childhood (10-15%) than in adult patients with B-NHL (30-40%). Involvement of the <italic>BCL6</italic> (3q27), <italic>BCL2</italic> (18q21) and to a lesser extent <italic>MYC</italic> (8q24) loci have been demonstrated in adult DLBCL. Chromosomal alterations associated with childhood DLBCL have not been well described and a study of 7 pediatric cases suggested that they could be distinct from those known to occur in adult DLBCL<xref rid="R23" ref-type="bibr">23</xref>.</p><p id="P5">We now report the cytogenetic results of 238 children and adolescents with localized, intermediate and advanced B-NHL treated on FAB/LMB 96 in a uniform manner that were reviewed by an international cytogenetic panel of experts and correlated with centrally reviewed pathology. We further characterize the non-random chromosomal alterations and analyze the prognostic significance of specific cytogenetic aberrations on the EFS.</p></sec><sec id="S2"><title>Patient and Methods</title><sec id="S3" sec-type="subjects"><title>FAB/LMB Patients</title><p id="P6">This study included children and adolescents with mature B-cell NHL registered and treated on the randomized international FAB/LMB 96 therapeutic trial with the collaboration of 3 pediatric cooperative groups: SFOP (Société Française d’Oncologie Pédiatrique), CCG (Children’s Cancer Group of the USA, Canada and Australia) and UKCCSG (United Kingdom Children’s Cancer Study Group). One thousand one hundred eleven non immunosuppressed patients under 18 (SFOP, UKCCSG) or 21 (CCG5961) years of age with newly diagnosed <italic>de novo</italic> mature B-cell lymphoma enrolled from May 1996 to June 2001 were eligible (SFOP: 385 cases; CCG5961: 531; UKCCSG: 195). International morphologic review and follow-up data were available in 1018 (92%). Patients were stratified into 3 risk groups <xref rid="R24" ref-type="bibr">24</xref>: A (resected stage I or completely resected abdominal stage II), B (non eligible for A and C), C (stage IV with CNS involvement and/or B-ALL) with treatment of progressive intensity <xref rid="R1" ref-type="bibr">1</xref>,<xref rid="R2" ref-type="bibr">2</xref>.</p></sec><sec id="S4"><title>Pathologic review</title><p id="P7">The pathological materials for each case were initially reviewed in each national cooperative group by at least two expert hematopathologists. A diagnosis was defined according to the REAL classification<xref rid="R4" ref-type="bibr">4</xref> which formed the basis of the new WHO classification<xref rid="R5" ref-type="bibr">5</xref>. All cases were then re-reviewed by the two other national group pathologists at a group review meeting. A consensus diagnosis was established for each case when all three national diagnoses were in agreement or when two of the three national expert groups were in agreement. When none of the three national diagnoses were in agreement a consensus diagnosis was reached following group review on a multi-headed microscope by all members of the reviewing committee<xref rid="R25" ref-type="bibr">25</xref>. <italic>A posteriori</italic>, due to the high incidence of DLBCL with 8q24/MYC rearrangement, all of the DLBCL with an 8q24/MYC translocation were reviewed again by the panel to exclude any cases of BL or BLL by morphology. Upon subsequent re-review by the international panel, all cases were confirmed histologically to be DLBCL based on morphologic features.</p></sec><sec id="S5"><title>Cytogenetic review</title><p id="P8">Abnormal karyotypes from 280 children enrolled in the FAB LMB96 study were collected by the cooperative groups. Inclusion criteria for the cytogenetic study were: (i) an abnormal karyotype from an involved tissue obtained at the time of primary diagnosis and before treatment; (ii) for each case, at least two karyograms representative of each abnormal clone reviewed by at least two experienced cancer cytogeneticists, one of whom was not from the submitting institution. The cytogenetic reviews were performed within the framework of each national therapeutic groups. The study was based solely on conventional chromosomal analysis with no FISH input. The karyotypes were described according to the 2005 International System for Human Cytogenetic Nomenclature<xref rid="R26" ref-type="bibr">26</xref> (<xref rid="SD2" ref-type="supplementary-material">Supplementary Table 1</xref>). Forty-two cases were excluded: 15 without any morphologic review, 26 without any cytogenetic review and 1 because the karyotype study was performed during treatment. Finally, 238 cases were included in this study, 121 from the SFOP group, 96 from the CCG and 21 from the UKCCSG. In 9 cases, a karyotype of at least 2 different samples from the same patient were available. The most complex karyotype was scored for inclusion in the prognostic analysis. In this study, the presence of more than 3 chromosomal alterations was considered to define a complex karyotype.</p></sec><sec id="S6" sec-type="results"><title>Statistics</title><p id="P9">Comparisons of the distribution of patients’ characteristics were performed using either the Chi-squared or Fisher’s exact test. The end-point of the prognostic analysis was event-free survival (EFS) which was defined as the minimum time between treatment start and progressive disease or relapse or second malignancy or death from any cause or the last follow-up contact for patients who did not experience any event. EFS was estimated with the Kaplan Meier method. Prognostic impact of each chromosomal abnormality was studied using Cox’s model with adjustment for the national cooperative group (SFOP, CCG, UKCCSG), the therapeutic groups (C standard treatment vs C reduced treatment vs A or B), the morphologic consensus diagnosis (DLBCL vs BL or BLL or not subclassified), the LDH level (>2 times the normal institutional value vs <=2N), CNS involvement and primary mediastinal localization. Individual chromosomal abnormalities with a p value <0.20 in this analysis were studied altogether in a Cox’s model in order to identify the independent prognostic factors. The variable “karyotype complexity” was then added in the model to determine whether the effect of the individual chromosomal abnormalities was independent of complexity or was related to their association with the cytogenetic complexity. A test for interaction was used to investigate if the impact on EFS of the significant chromosomal abnormality was substantially different in BL or DLBCL. The reported p-values are two-sided.</p></sec></sec><sec sec-type="results" id="S7"><title>Results</title><sec id="S8"><title>Patient Demographics (<xref rid="T1" ref-type="table">Table 1</xref>)</title><p id="P10">Median age was 9.1 years (range [2-20]); male / female sex ratio was 3.1. Seventy-six percent of cases were classified as BL, 8% BLL, 13% DLBCL and 3% not sub classified. Five percent were treated according to group A regimen, 55% group B and 40% group C. As compared to the other 780 patients of the FAB/LMB96 study, there was a significant over-representation of group C, especially patients with B-ALL, with LDH level > 2N and with CNS involvement. Otherwise patients in this cytogenetic analysis had an increased frequency of BL compared to the other patients treated on the FAB/LMB 96 study (<xref rid="T1" ref-type="table">Table 1</xref>). After adjustment for risk group and LDH level, the EFS of patients included in the cytogenetic study did not significantly differ from the EFS of the other patients treated on the FAB/LMB 96 study</p></sec><sec id="S9"><title>Characterization of cytogenetic abnormalities (<xref rid="F1" ref-type="fig">Figure 1</xref>)</title><p id="P11">Rearrangement of the chromosomal band 8q24 (rearranged 8q24), site of the <italic>MYC</italic> locus, with the different immunoglobulin gene loci was detected in 84% cases: 93% of BL, 83% of BLL and 33% of DLBCL. Rearranged 8q24 was associated with other chromosomal aberrations in 69% of cases [BL: 64%, BLL: 93%, DLBCL: 100%]. The main associated clonal structural alteration was +1q followed by +7q, del(13q) and del(6q). In the absence of rearranged 8q24, karyotypes were more complex (57% versus 33%, p=0.006), there was more aneuploidy (70% versus 30%, p<0.0001), and the pattern of associated abnormalities was quite different with a higher incidence of der(11q), +12q and del(6q) and a lower proportion of +1q. The pattern of chromosomal alterations also varied according to the morphological subtype, except for del(13q) and +7q, which occurred in similar proportions in BL and in DLBCL. The main secondary alteration in BL was +1q (29%). Dup(1q) was only identified in BL while del(6q), der(11q) and +12 were significantly more frequent in DLBCL (43%, 27%, 23% respectively). The DLBCL karyotypes were significantly more complex and more aneuploid than BL (both 80% vs 27%, p<0.0001). The small group of BLL appeared heterogeneous, sharing characteristics of BL as well as of DLBCL (<xref rid="F1" ref-type="fig">Figure1</xref>). Gain of the long arm of chromosome 1 was due to dup(1q) in 43/65 cases (66%). Alterations of chromosome 13q were very heterogeneous. The majority (33/38) resulted in 13q deletions either isolated or due to various unbalanced translocations without obvious recurrent breakpoints. The most commonly deleted band was 13q34 (82%). Gain of 7q (36 cases) was due to whole chromosome trisomy (19 cases), unbalanced translocations with different partners (12 cases), isochromosome 7q (4 cases), interstitial 7q du-/triplications (3 cases). Coexistence of 2 different mechanisms of +7q was observed in 2 cases leading to 7q tetrasomy. The minimal region of gain was restricted to 7q21q22. The 13q and 7q alterations were frequently encountered in a complex karyotype (88% and 58% respectively). A group of 33 cases had loss of part or all of the long arm of a chromosome 6, del(6q). In 28 of these, there appeared to be a simple deletion; in the remaining 5 the loss occurred as the result of an unbalanced translocation. Two different rearrangements of chromosome 11 were detected: deletions (14 cases) and 11q gains (5 cases). The most frequent breakpoint was 11q23 (63%). Gain of 12q was due to whole chromosome trisomy in 15/16 cases. Lastly, complexity was associated with aneuploidy (65%), del(13q) (34%), del(6q) (28%) and +7q (23%). The aneuploidy was usually due to hyperdiploidy (71%).</p></sec><sec id="S10"><title>Prognostic significance of cytogenetic abnormalities</title><p id="P12">The median follow-up time of the subset of 238 patients with both cytogenetic and morphologic reviews was 4.5 years [range: 10 months – 8 years]. There were 43 events. The cytogenetic abnormalities associated with a significantly worse EFS were aneuploidy, complexity, rearranged 8q24, del(13q), +7q and der(3q) (<xref rid="T2" ref-type="table">Table 2</xref>).</p><p id="P13">The combined analysis of the different cytogenetic abnormalities showed that rearranged 8q24, del(13q) and +7q were independently associated with a worse EFS: their respective hazard ratios (HR) [95%CI] were 6.1 [1.2-31] (p=0.028), 4.0 [1.9-8.6] (p=0.0003) and 2.5 [1.2-5.2] (p=0.015), respectively. The 4-year EFS of patients with rearranged 8q24 was 79.6% versus 94.6% in the other patients (<xref rid="F2" ref-type="fig">Figure 2A</xref>). In patients with a +7q abnormality, the EFS was 72.2% versus 83.6% in patients without this abnormality. Similarly in patients with a del(13q) the EFS was 63.6% versus 84.9% in the rest of the group. Furthermore, patients with del(13q) had a significantly inferior response to COP reduction therapy after one week of therapy (15% vs 2%, p<0.004). Complexity of the karyotype was associated with a significantly worse EFS (HR=3.2, p=0.0005) (<xref rid="T2" ref-type="table">Table 2</xref>): the EFS of patients with a complex karyotype was 72.1 vs 87.4% without (<xref rid="F2" ref-type="fig">Figures 2</xref>). However, when complexity was added to the model including these 3 chromosomal alterations, the prognostic effect of each of them remained significantly associated with EFS (respective HR were 5.8, 2.5 and 2.5), and the hazard ratio of complexity decreased to 2.0 [95%CI=0.92-4.3] (p=0.08).</p><p id="P14">The prognostic effect of del(13q), +7q and karyotype complexity did not differ between BL and DLBCL, whereas the adverse prognostic effect of rearranged 8q24 was only observed in DLBCL (interaction test, p=0.19). In BL, the 4 year EFS was 83.4 and 84.6% with and without rearranged 8q24. Although the numbers were very small, the EFS in DLBCL with and without rearranged 8q24 was 50% (5 events /10 patients) vs 100% (0 event /20 patients) (<xref rid="F3" ref-type="fig">Figures 3</xref>).</p></sec></sec><sec sec-type="discussion" id="S11"><title>Discussion</title><p id="P15">Childhood mature B-cell lymphomas currently have a favorable outcome with present therapeutic strategies, but intensive chemotherapy is associated with significant morbidity<xref rid="R1" ref-type="bibr">1</xref>-<xref rid="R3" ref-type="bibr">3</xref>,<xref rid="R24" ref-type="bibr">24</xref>,<xref rid="R27" ref-type="bibr">27</xref>. The principal objective of the international randomized FAB LMB96 study was to try to diminish treatment intensity without jeopardizing survival<xref rid="R1" ref-type="bibr">1</xref>-<xref rid="R3" ref-type="bibr">3</xref>. Among the secondary aims of the study was to identify prognostic factors to tailor further treatment and develop more risk adaptive therapy.</p><p id="P16">This is the first large cytogenetic study performed on such an international randomized trial in children and adolescents with mature B-cell lymphoma treated in a uniform manner. The multivariate analysis showed that specific karyotype abnormalities, rearranged 8q24, +7q, del(13q) have an independent prognostic significance in childhood mature B-cell lymphoma. Their hazard ratios of greater than 2.5 were in the same range as some other clinical and biological prognostic risk factors that we have previously identified such as CNS disease, COP response, risk groups and initial LDH level<xref rid="R1" ref-type="bibr">1</xref>-<xref rid="R3" ref-type="bibr">3</xref>. Further, the complete cytogenetic characterization in the subgroup of children with B-NHL contributed to the identification of distinctive patterns of chromosomal alterations that provide additional diagnostic information to the morphologic classification.</p><p id="P17">We did not detect any prognostic value of 1q gain, though the size of the series was sufficient to detect any significant effect of this common chromosomal abnormality. This is in contrast to a smaller study of 46 sporadic BL that had previously identified +1q to be a poor risk factor but treated with heterogeneous therapeutic schemes<xref rid="R20" ref-type="bibr">20</xref>. This discrepancy may be due to improvement in the recent development of short intensive chemotherapy utilizing fractionated cyclophosphamide, higher doses of methotrexate and in more advanced patients high dose fractionated and continuous infusion ARA-C, which could have abolished the effect of this chromosomal abnormality.</p><p id="P18">Complexity of the karyotype could be a measure of the number of the oncogenetic steps but also could reflect the genetic instability of tumors. In our series, the prognostic effect of complexity was partly explained by the role of del(13q) and to a lesser extent of +7q. Both of these alterations were detected in BL and DLBCL in similar proportions and were usually associated with complexity. These observations suggest that del(13q) and +7q could be secondary events associated with tumor progression of childhood B-cell mature lymphomas regardless of the morphologic subclassification.</p><p id="P19">Although we detected two partial 13q duplications leading to 13q11q22 trisomy as reported in Barin C <italic>et al</italic>.<xref rid="R28" ref-type="bibr">28</xref>, most of the 13q alterations resulted in a del(13q) involving chromosomal band 13q34 and to a lesser extent 13q14. Chromosome 13 candidate genes include <italic>BAFF</italic> (13q32q34), which recently has been shown to be involved in BL apoptosis<xref rid="R29" ref-type="bibr">29</xref>, and a new family of regulatory micro-RNA genes (miR genes), which have been identified at different genomic regions involved in cancers and specifically on 13q14<xref rid="R30" ref-type="bibr">30</xref>.</p><p id="P20">As expected, rearranged 8q24 was cytogenetically detected in 93% of BL, most of them resulting from a t(8;14) translocation. The incidence rates of variant translocations t(8;22) and t(2;8) were lower than previously reported (11% and 5.6% respectively)<xref rid="R13" ref-type="bibr">13</xref>. The 13 cases classified as BL without an obvious <italic>MYC</italic> locus rearrangement (7% in this series) shared a similar pattern of chromosomal alterations with the 169 BL with rearranged 8q24, except for more frequent aneuploidy and presence of der(11q), although not significant. This observation raises the question if the BL without rearranged 8q24 truly belong to the Burkitt entity (with possible cryptic <italic>MYC</italic> rearrangement potentially detectable by FISH) or if they are actually some other aggressive mature B-cell proliferations sharing morphologic similarities with BL. It is noteworthy that a recent gene expression profiling study confirmed the existence of lymphomas with the molecular signature of BL without cytogenetically detectable <italic>MYC</italic> rearrangement<xref rid="R31" ref-type="bibr">31</xref> The significant difference in EFS associated with a rearranged 8q24 occurred in the small number of patients in the DLBCL subgroup where presumably it may represent a secondary event in contrast to likely being a primary event in the Burkitt subgroup. This assumption is also supported by the detection of a different molecular signature between BL and DLBCL with <italic>MYC</italic> rearrangement<xref rid="R32" ref-type="bibr">32</xref>. This needs to be confirmed in a large series and analyzed by DLBCL subtypes including germinal center (GC) and activated B-cell like (ABC).</p><p id="P21">The pattern of chromosomal alterations in this childhood DLBCL series was quite distinct from those reported in adult patients. Alterations of loci containing oncogenes known to play a major role in adult DLBCL lymphomagenesis, such as <italic>BCL6</italic> (3q27) and <italic>BCL2</italic> (18q21), were very rare (each < 7%) in this childhood series. In particular, no concurrent t(14;18) and R8q24 were detected, which is known to be a poor-outlook combination in DLBCL. Conversely, involvement of the <italic>MYC</italic> (8q24) locus was much more frequent (33%) than the 5-10% reported in adult DLBCL<xref rid="R33" ref-type="bibr">33</xref>,<xref rid="R34" ref-type="bibr">34</xref>. We and others have recently reported an increase in frequency of the GC vs ABC subtype of DLBCL in children and adolescents compared to previous reports in adults<xref rid="R35" ref-type="bibr">35</xref>-<xref rid="R37" ref-type="bibr">37</xref>.</p><p id="P22">Our data showed that specific cytogenetic findings at diagnosis are useful for improving sub-classification of childhood mature B-cell lymphomas, in conjunction with morphology and immunophenotyping. Furthermore, we have found that cytogenetic aberrations are independent prognostic variables in childhood mature B-cell NHL. In particular, we showed the independent importance of rearranged 8q24, +7q, del(13)(q34). The prognostic effect of complexity was partly explained by the role of del(13q) and to a lesser extent of +7q. These results emphasize the biological heterogeneity of childhood mature B-cell NHL and the impact of cytogenetics in prognostic stratification. In this latter purpose, conventional cytogenetics can be supplemented by interphase FISH to enhance detection of relevant chromosomal alterations (such as 8q24 translocations and +7q). High resolution genome-wide array in parallel with gene expression profiling should allow more precise characterization of heterogeneous chromosomal abnormalities, especially complexity and del(13q), in order to search for candidate genes and deregulated cellular pathways. If other studies confirm these results, future therapeutic strategies could incorporate the results of these cytogenetic findings and investigate whether alternative treatment strategies would improve the prognosis in subgroups of patients with poor risk cytogenetic factors.</p></sec><sec sec-type="supplementary-material" id="S12"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD2"><label>1</label><media xlink:href="NIHMS107551-supplement-1.xls" mimetype="application" mime-subtype="vnd.ms-excel" xlink:type="simple" id="d37e603" position="anchor"></media></supplementary-material></sec></body><back><ack id="S17"><p>The authors would like to thank the other members of the international morphologic review panel: M.J. Terrier-Lacombe, C. Bayle, B. Felman (SFOP), M. Lones (CCG) and A. Wotherspoon UKCCSG). The authors would like to further thank the data managers of the SFOP, CCG and UKCCSG cooperative groups, Virginia Davenport and Lauren Harrison for their active and helpful support of COG part of the study and all the investigators who treated the patients and participated in the study.</p><p><bold>Acknowledgments for research support</bold> : Supported by grants from the Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Department of Health and Human Services (COG); Cancer Research Campaign, (UKCSSG); and Association pour la Recherche contre le Cancer), La Ligue Nationale Contre le Cancer, Institut Gustave Roussy (SFOP) and COG Grant CA 98543. A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at : <ext-link ext-link-type="uri" xlink:href="http://www.childrensoncologygroup.org/admin/grantinfo.htm">http://www.childrensoncologygroup.org/admin/grantinfo.htm</ext-link></p></ack><fn-group><fn id="FN4" fn-type="presented-at"><p>Presented in part at the 43<sup>nd</sup> meeting of the American Society of Hematology (ASH), December 2003, Philadelphia, USA, and at the 9<sup>th</sup> International Conference on Malignant Lymphoma (9-ICML), June 2005, Lugano, Switzerland.</p></fn><fn id="FN5" fn-type="supplementary-material"><p><bold>Supplementary Information</bold> accompanies the paper on the Leukemia website (<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/leu">http://www.nature.com/leu</ext-link>)</p></fn></fn-group><app-group><app id="APP1"><title>Appendix: contributing cytogeneticists and their institutions by alphabetic order (* cytogeneticists who participated on the panel of reviewers)</title><sec id="S13"><title>SFOP</title><p id="P23">H Avet-Loiseau (CHU, Nantes); L Baranger* (CHU, Angers); C Barin (CHU, Tours); C Bastard* (CHU, Rouen); A Bernheim* (Institut Gustave Roussy,Villejuif); MF Berthéas (Hopital Nord, St Etienne); C Bilhou-Nabera (CHU Pessac, Bordeaux); C Borie (Hopital Robert Debre, Paris); J Boyer (CHU, Brest); F Brizard (Hopital J. Bernard, Poitiers); E Caillet-Bauchu* (CHU Lyon Sud); AM Capdano (Hopital De La Timone, Marseille); MA Collonge-Rame (Hopital St Jacques, Besançon); P Cornillet* (CHU, Reims); J Couturier (Institut Curie, Paris); N Dastugue (CHU Purpan, Toulouse); A Daudignon (CHU, Valenciennes); N Gachard (CHU Dupuytren, Limoges); MJ Grégoire CHRU Nancy); P Heimann (Institut Jules Bordet, Bruxelles, Belgique); C Henry (CHRU Pontchaillou, Rennes); JL Laï (CHU Jeanne de Flandre, Lille); D Leroux (Hopital Michalon, Grenoble); M Lessard (Hospices Civils, Strasbourg); I Luquet* (CHU, Reims); CHM Mellink (Emma Kinderziekenhuis EK2/AMC, Amsterdam, Netherlands); N Nadal (Hopital Nord, St Etienne); MP Pagès* (Hopital Debrousse, Lyon); D Penther (CHU, Rouen); B Perissel (Hotel Dieu, Clermont Ferrand); C Perrot (CHU Saint-Antoine, Paris); S Raynaud (CHU, Nice); P Talman (CHU, Nantes); S Taviaux* (Hopital St Charles, Montpellier); I Tigaud* (CHU E Herriot, Lyon); J Van den Akker (CHU Saint-Antoine, Paris).</p></sec><sec id="S14"><title>CCG</title><p id="P24">J Beigel* (Children’s Hospital of Philadelphia, Philadelphia PA); P Benn (University of Connecticut, Farmington CT); E Cantu, (Children’s Hospital Medical Center, Akron OH); K Carlson (University of Chicago, Chicago IL); L Cooley (Children’s Mercy Hospital, Kansas City KS); A Dawson (Cancer Care Manitoba, Winnipeg MB); VG Dev (Genetics Associates, Nashville TN); G Dewald (Mayo Clinic, Rochester MN); T Drumheller (Valley Children’s Hospital, Fresno CA); J Fink (Hennepin, Minneapolis MN); I Gadi (Genetics Associates, Nashville TN); J Hanna (Sacred Heart Hospital, Spokane WA); A Glassman (MD Anderson, Houston TX); K Harrison (Loyola University, Chicago IL); N Heerema* (Indiana University, Indianapolis IN); J Higgins (Spectrum Health, Grand Rapids MI); R Higgins (Allina Health System, Minneapolis MN); B Hirsch* (University of Minnesota, Minneapolis MN); D Horsman (British Columbia Cancer Agency, Vancouver BC); D Kalousek (British Columbia Children’s Hospital, Vancouver BC); P Koduru (Winthrop, New York NY); R Lebo (Children’s Hospital Medical Center, Akron OH); X Li (Kaiser Permenente, anta Clara CA); RE Magenis* (Oregon Health Sciences University, Protland OR); K McFadden (British Columbia Children’s Hospital, Vancouver BC); L McGavron* (University of Colorado Health Science Center, Denver CO); L McMorrow (Thomas Jefferson University, Philadelphia PA); A Murch (King Edward Memorial Hospital, Melbourne Australia); K Opheim (University of Washington, Seattle WA); D Panzar (British Columbia Children’s Hospital, Vancouver BC); L Pasztor (Palo Verde Laboratory, Phoenix AZ); A Pettigrew (University of Kentucky, Lexington KY); C Philips (Emory University, Atlanta GA); K Rao* (University of North Carolina, Durham NC); PN Rao (University of California at LosAngeles, Los Angeles CA); D Rouston* (University of Michigan, Ann Arbor MI); W Sanger* (University of Nebraska, Omaha NB); KL Satya-Prakash (Medical College of Georgia, Augusta GA); S Schwartz (Case Western Reserve University, Cleveland OH); GS Sekhon (University of Wisconsin, Madison WI); G Shaw (Marshfield Laboratories, Marshfield WI); S Shekter-Levin (Magee Women’s Hospital, Pittsburg PA); N Spinner (Children’s Hospital of Philadelphia, Philadelphia PA); W Stanley (Genetics IVF, Fairfax VA); P Storto (Michigan State University, Lansing MI); M Thangavelu (Genzyme, Orange County CA); K Theil* (The Ohio State University, Columbus OH); G Vance (Indiana University, Indianapolis IN); D VanDyke (Henry Ford Hospital, Detroit MI); T Zadeh (Genetics Center, CA, Orange CA).</p></sec><sec id="S15"><title>UKCCSG : cytogeneticists belong to the UK Cancer Cytogenetics Group (UKCCG)</title><p id="P25">K Andrews (Addenbrookes Hospital, Cambridge); M Booth (University Hospital of Wales, Cardiff); N Bown (Institute of Human Genetics, Newcastle); T Davies (Southmead Hospital, Bristol); E Grace (Western General Hospital;Edinburgh); M Griffiths (Birmingham Women’s Hospital, Birmingham); P Howard (Liverpool Women’s Hospital, Liverpool); D Hughes (The Churchill Hospital, Oxford); H Kempski (The Hospital for Sick Children, Great Ormond Street, London); D Lillington (St. Barts Hospital, London); G Lowther (Yorkhill Hospital, Glasgow); K Martin (Nottingham City Hospital, Nottingham); P Roberts (St. James Hospital, Dublin); F Ross (Salisbury District Hospital, Salisbury); J Sadler (Leicester Royal Infirmary, Leicester); R Stallings (St. James Hospital, Dublin); D Stevenson (Grampian University Hospitals, Aberdeen); J Swansbury* (The Royal Marsden Hospital, Sutton); P Talley* (Sheffield Children’s Hospital, Sheffield); N Telford (The Christie Hospital, Manchester); H Walker (University College Hospital, London).</p></sec></app></app-group><ref-list><ref id="R1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patte</surname><given-names>C</given-names></name><name><surname>Auperin</surname><given-names>A</given-names></name><name><surname>Gerrard</surname><given-names>M</given-names></name><name><surname>Michon</surname><given-names>J</given-names></name><name><surname>Pinkerson</surname><given-names>CR</given-names></name><name><surname>Sposto</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin’s lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients</article-title><source>Blood</source><year>2007</year><volume>109</volume><fpage>2773</fpage><lpage>2780</lpage><pub-id pub-id-type="pmid">17132719</pub-id></element-citation></ref><ref id="R2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cairo</surname><given-names>MS</given-names></name><name><surname>Gerrard</surname><given-names>M</given-names></name><name><surname>Sposto</surname><given-names>R</given-names></name><name><surname>Auperin</surname><given-names>A</given-names></name><name><surname>Pinkerson</surname><given-names>CR</given-names></name><name><surname>Michon</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Results of a randomized international study of high risk central nervous system B-non-Hodgkin’s lymphoma and B-acute lymphoblastic leukemia in children and adolescents</article-title><source>Blood</source><year>2007</year><volume>109</volume><fpage>2736</fpage><lpage>2743</lpage><pub-id pub-id-type="pmid">17138821</pub-id></element-citation></ref><ref id="R3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gerrard</surname><given-names>M</given-names></name><name><surname>Cairo</surname><given-names>MS</given-names></name><name><surname>Weston</surname><given-names>C</given-names></name><name><surname>Auperin</surname><given-names>A</given-names></name><name><surname>Pinkerton</surname><given-names>R</given-names></name><name><surname>Lambilliote</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 International Study</article-title><source>Br J Haematol</source><year>2008</year><volume>141</volume><fpage>840</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">18371107</pub-id></element-citation></ref><ref id="R4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Harris</surname><given-names>NL</given-names></name><name><surname>Jaffe</surname><given-names>ES</given-names></name><name><surname>Stein</surname><given-names>H</given-names></name><name><surname>Banks</surname><given-names>PM</given-names></name><name><surname>Chan</surname><given-names>JK</given-names></name><name><surname>Cleary</surname><given-names>ML</given-names></name><etal></etal></person-group><article-title>A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group</article-title><source>Blood</source><year>1994</year><volume>84</volume><fpage>1361</fpage><lpage>1392</lpage><pub-id pub-id-type="pmid">8068936</pub-id></element-citation></ref><ref id="R5"><label>5</label><element-citation publication-type="book"><person-group person-group-type="editor"><name><surname>Jaffe</surname><given-names>ES</given-names></name><name><surname>Harris</surname><given-names>NL</given-names></name><name><surname>Stein</surname><given-names>H</given-names></name><name><surname>Vardiman</surname><given-names>JW</given-names></name></person-group><article-title>World Health Organization Classification of tumors</article-title><source>Pathology & genetics of tumours of haematopoietic and lymphoid tissues</source><publisher-loc>Lyon</publisher-loc><publisher-name>IARCPress</publisher-name><year>2001</year><fpage>181</fpage><lpage>184</lpage></element-citation></ref><ref id="R6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lenoir</surname><given-names>GM</given-names></name><name><surname>Preud’homme</surname><given-names>JL</given-names></name><name><surname>Bernheim</surname><given-names>A</given-names></name><name><surname>Berger</surname><given-names>R</given-names></name></person-group><article-title>Correlation between immunoglobulin light chain expression and variant translocation in Burkitt’s lymphoma</article-title><source>Nature</source><year>1982</year><volume>298</volume><fpage>474</fpage><lpage>476</lpage><pub-id pub-id-type="pmid">6806672</pub-id></element-citation></ref><ref id="R7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Battey</surname><given-names>J</given-names></name><name><surname>Moulding</surname><given-names>C</given-names></name><name><surname>Taub</surname><given-names>R</given-names></name><name><surname>Murphy</surname><given-names>W</given-names></name><name><surname>Stewart</surname><given-names>T</given-names></name><name><surname>Potter</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma</article-title><source>Cell</source><year>1983</year><volume>34</volume><fpage>779</fpage><lpage>787</lpage><pub-id pub-id-type="pmid">6414718</pub-id></element-citation></ref><ref id="R8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zech</surname><given-names>L</given-names></name><name><surname>Haglund</surname><given-names>U</given-names></name><name><surname>Nilsson</surname><given-names>K</given-names></name><name><surname>Klein</surname><given-names>G</given-names></name></person-group><article-title>Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas</article-title><source>Int J Cancer</source><year>1976</year><volume>17</volume><fpage>47</fpage><lpage>56</lpage><pub-id pub-id-type="pmid">946170</pub-id></element-citation></ref><ref id="R9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bernheim</surname><given-names>A</given-names></name><name><surname>Berger</surname><given-names>R</given-names></name><name><surname>Lenoir</surname><given-names>G</given-names></name></person-group><article-title>Cytogenetic studies on African Burkitt’s lymphoma cell lines: t(8;14), t(2;8) and t(8;22) translocations</article-title><source>Cancer Genet Cytogenet</source><year>1981</year><volume>3</volume><fpage>307</fpage><lpage>315</lpage><pub-id pub-id-type="pmid">7260888</pub-id></element-citation></ref><ref id="R10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blum</surname><given-names>KA</given-names></name><name><surname>Lozanski</surname><given-names>G</given-names></name><name><surname>Byrd</surname><given-names>JC</given-names></name></person-group><article-title>Adult Burkitt leukemia and lymphoma</article-title><source>Blood</source><year>2004</year><volume>104</volume><fpage>3009</fpage><lpage>3020</lpage><pub-id pub-id-type="pmid">15265787</pub-id></element-citation></ref><ref id="R11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilda</surname><given-names>M</given-names></name><name><surname>Bruch</surname><given-names>J</given-names></name><name><surname>Harder</surname><given-names>L</given-names></name><name><surname>Rawer</surname><given-names>D</given-names></name><name><surname>Reiter</surname><given-names>A</given-names></name><name><surname>Borkhardt</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Inactivation of the ARF-MDM-2-p53 pathway in sporadic Burkitt’s lymphoma in children</article-title><source>Leukemia</source><year>2004</year><volume>18</volume><fpage>584</fpage><lpage>588</lpage><pub-id pub-id-type="pmid">14712292</pub-id></element-citation></ref><ref id="R12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lindstrom</surname><given-names>MS</given-names></name><name><surname>Wiman</surname><given-names>KG</given-names></name></person-group><article-title>Role of genetic and epigenetic changes in Burkitt lymphoma</article-title><source>Semin Cancer Biol</source><year>2002</year><volume>12</volume><fpage>381</fpage><lpage>387</lpage><pub-id pub-id-type="pmid">12191637</pub-id></element-citation></ref><ref id="R13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berger</surname><given-names>R</given-names></name><name><surname>Bernheim</surname><given-names>A</given-names></name></person-group><article-title>Cytogenetics of Burkitt’s lymphoma-leukaemia: a review</article-title><source>IARC Sci Publ</source><year>1985</year><volume>60</volume><fpage>65</fpage><lpage>80</lpage><pub-id pub-id-type="pmid">2998996</pub-id></element-citation></ref><ref id="R14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berger</surname><given-names>R</given-names></name><name><surname>Le Coniat</surname><given-names>M</given-names></name><name><surname>Derre</surname><given-names>J</given-names></name><name><surname>Vecchione</surname><given-names>D</given-names></name></person-group><article-title>Secondary nonrandom chromosomal abnormalities of band 13q34 in Burkitt lymphoma-leukemia</article-title><source>Genes Chromosomes Cancer</source><year>1989</year><volume>1</volume><fpage>115</fpage><lpage>118</lpage><pub-id pub-id-type="pmid">2487150</pub-id></element-citation></ref><ref id="R15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lai</surname><given-names>JL</given-names></name><name><surname>Fenaux</surname><given-names>P</given-names></name><name><surname>Zandecki</surname><given-names>M</given-names></name><name><surname>Nelken</surname><given-names>B</given-names></name><name><surname>Huart</surname><given-names>JJ</given-names></name><name><surname>Deminatti</surname><given-names>M</given-names></name></person-group><article-title>Cytogenetic studies in 30 patients with Burkitt’s lymphoma or L3 acute lymphoblastic leukemia with special reference to additional chromosome abnormalities</article-title><source>Ann Genet</source><year>1989</year><volume>32</volume><fpage>26</fpage><lpage>32</lpage><pub-id pub-id-type="pmid">2751244</pub-id></element-citation></ref><ref id="R16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kornblau</surname><given-names>SM</given-names></name><name><surname>Goodacre</surname><given-names>A</given-names></name><name><surname>Cabanillas</surname><given-names>F</given-names></name></person-group><article-title>Chromosomal abnormalities in adult non-endemic Burkitt’s lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature</article-title><source>Hematol Oncol</source><year>1991</year><volume>9</volume><fpage>63</fpage><lpage>78</lpage><pub-id pub-id-type="pmid">1869243</pub-id></element-citation></ref><ref id="R17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johansson</surname><given-names>B</given-names></name><name><surname>Mertens</surname><given-names>F</given-names></name><name><surname>Mitelman</surname><given-names>F</given-names></name></person-group><article-title>Cytogenetic evolution patterns in non-Hodgkin’s lymphoma</article-title><source>Blood</source><year>1995</year><volume>86</volume><fpage>3905</fpage><lpage>3914</lpage><pub-id pub-id-type="pmid">7579360</pub-id></element-citation></ref><ref id="R18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berger</surname><given-names>R</given-names></name><name><surname>Bernheim</surname><given-names>A</given-names></name></person-group><article-title>Is there a functional equivalence between abnormalities of the long arm of chromosome 1 and the presence of Epstein-Barr virus in continuous lines of Burkitt’s lymphoma?</article-title><source>C R Acad Sci III</source><year>1984</year><volume>298</volume><fpage>143</fpage><lpage>145</lpage><pub-id pub-id-type="pmid">6324967</pub-id></element-citation></ref><ref id="R19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Knutsen</surname><given-names>T</given-names></name></person-group><article-title>Cytogenetic changes in the progression of lymphoma</article-title><source>Leuk Lymphoma</source><year>1998</year><volume>31</volume><fpage>1</fpage><lpage>19</lpage><pub-id pub-id-type="pmid">9720711</pub-id></element-citation></ref><ref id="R20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Garcia</surname><given-names>JL</given-names></name><name><surname>Hernandez</surname><given-names>JM</given-names></name><name><surname>Gutierrez</surname><given-names>NC</given-names></name><name><surname>Flores</surname><given-names>T</given-names></name><name><surname>Gonzalez</surname><given-names>D</given-names></name><name><surname>Calasanz</surname><given-names>MJ</given-names></name><etal></etal></person-group><article-title>Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt’s lymphoma. A cytogenetic and comparative genomic hybridization study</article-title><source>Leukemia</source><year>2003</year><volume>17</volume><fpage>2016</fpage><lpage>2024</lpage><pub-id pub-id-type="pmid">14513052</pub-id></element-citation></ref><ref id="R21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lones</surname><given-names>MA</given-names></name><name><surname>Sanger</surname><given-names>WG</given-names></name><name><surname>Le Beau</surname><given-names>MM</given-names></name><name><surname>Heerema</surname><given-names>NA</given-names></name><name><surname>Sposto</surname><given-names>R</given-names></name><name><surname>Perkins</surname><given-names>SL</given-names></name><etal></etal></person-group><article-title>Children’s Cancer Group Study CCG-E08. Chromosome abnormalities may correlate with prognosis in Burkitt/Burkitt-like lymphomas of children and adolescents: a report from Children’s Cancer Group Study CCG-E08</article-title><source>J Pediatr Hematol Oncol</source><year>2004</year><volume>26</volume><fpage>169</fpage><lpage>178</lpage><pub-id pub-id-type="pmid">15125609</pub-id></element-citation></ref><ref id="R22"><label>22</label><element-citation publication-type="confproc"><person-group person-group-type="author"><name><surname>Heerema</surname><given-names>NA</given-names></name><name><surname>Bernheim</surname><given-names>A</given-names></name><name><surname>Lim</surname><given-names>MS</given-names></name><name><surname>Look</surname><given-names>AT</given-names></name><name><surname>Pasqualucci</surname><given-names>L</given-names></name><name><surname>Raetz</surname><given-names>E</given-names></name><etal></etal></person-group><conf-name>State of the Art and Future Needs in Cytogenetic/Molecular Genetics/Arrays in childhood lymphoma: Summary report of workshop at the First International Symposium on childhood and adolescent non-Hodgkin lymphoma</conf-name><conf-date>April 9, 2003</conf-date><conf-loc>New York City, NY</conf-loc><source>Pediatr Blood Cancer</source><year>2005</year><volume>45</volume><fpage>616</fpage><lpage>622</lpage><pub-id pub-id-type="pmid">16127683</pub-id></element-citation></ref><ref id="R23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dave</surname><given-names>BJ</given-names></name><name><surname>Weisenburger</surname><given-names>DD</given-names></name><name><surname>Higgins</surname><given-names>CM</given-names></name><name><surname>Pickering</surname><given-names>DL</given-names></name><name><surname>Hess</surname><given-names>MM</given-names></name><name><surname>Chan</surname><given-names>WC</given-names></name><etal></etal></person-group><article-title>Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults</article-title><source>Cancer Genet Cytogenet</source><year>2004</year><volume>153</volume><fpage>115</fpage><lpage>121</lpage><pub-id pub-id-type="pmid">15350300</pub-id></element-citation></ref><ref id="R24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patte</surname><given-names>C</given-names></name><name><surname>Auperin</surname><given-names>A</given-names></name><name><surname>Michon</surname><given-names>J</given-names></name><name><surname>Behrendt</surname><given-names>H</given-names></name><name><surname>Leverger</surname><given-names>G</given-names></name><name><surname>Frappaz</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>The Société Française d’Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia</article-title><source>Blood</source><year>2001</year><volume>97</volume><fpage>3370</fpage><lpage>3379</lpage><pub-id pub-id-type="pmid">11369626</pub-id></element-citation></ref><ref id="R25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lones</surname><given-names>MA</given-names></name><name><surname>Auperin</surname><given-names>A</given-names></name><name><surname>Raphael</surname><given-names>M</given-names></name><name><surname>McCarthy</surname><given-names>K</given-names></name><name><surname>Perkins</surname><given-names>SL</given-names></name><name><surname>MacLennan</surname><given-names>KA</given-names></name><etal></etal></person-group><article-title>Mature B-cell lymphoma/leukemia in children and adolescents: intergroup pathologist consensus with the revised European-American lymphoma classification</article-title><source>Ann Oncol</source><year>2000</year><volume>11</volume><fpage>47</fpage><lpage>51</lpage><pub-id pub-id-type="pmid">10690386</pub-id></element-citation></ref><ref id="R26"><label>26</label><element-citation publication-type="book"><person-group person-group-type="editor"><name><surname>Shaffer</surname><given-names>LG</given-names></name><name><surname>Tommerup</surname><given-names>N</given-names></name></person-group><collab>An International System for Human Cytogenetic Nomenclature</collab><source>Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature</source><publisher-loc>Basel</publisher-loc><publisher-name>S Karger</publisher-name><year>2005</year></element-citation></ref><ref id="R27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reiter</surname><given-names>A</given-names></name><name><surname>Schrappe</surname><given-names>M</given-names></name><name><surname>Tiemann</surname><given-names>M</given-names></name><name><surname>Ludwig</surname><given-names>WD</given-names></name><name><surname>Yakisan</surname><given-names>E</given-names></name><name><surname>Zimmermann</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster Group trial NHL-BFM 90</article-title><source>Blood</source><year>1999</year><volume>94</volume><fpage>3294</fpage><lpage>3306</lpage><pub-id pub-id-type="pmid">10552938</pub-id></element-citation></ref><ref id="R28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barin</surname><given-names>C</given-names></name><name><surname>Valtat</surname><given-names>C</given-names></name><name><surname>Briault</surname><given-names>S</given-names></name><name><surname>Bremont</surname><given-names>JL</given-names></name><name><surname>Petit</surname><given-names>A</given-names></name><name><surname>Lejars</surname><given-names>O</given-names></name><etal></etal></person-group><article-title>Structural rearrangements of chromosome 13 as additional abnormalities in Burkitt lymphoma and type 3 acute lymphoblastic leukemia</article-title><source>Cancer Genet Cytogenet</source><year>1992</year><volume>60</volume><fpage>206</fpage><lpage>209</lpage><pub-id pub-id-type="pmid">1606568</pub-id></element-citation></ref><ref id="R29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ogden</surname><given-names>CA</given-names></name><name><surname>Pound</surname><given-names>JD</given-names></name><name><surname>Batth</surname><given-names>BK</given-names></name><name><surname>Owens</surname><given-names>S</given-names></name><name><surname>Johannessen</surname><given-names>I</given-names></name><name><surname>Wood</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt’s lymphoma</article-title><source>J Immunol</source><year>2005</year><volume>174</volume><fpage>3015</fpage><lpage>3023</lpage><pub-id pub-id-type="pmid">15728515</pub-id></element-citation></ref><ref id="R30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Calin</surname><given-names>GA</given-names></name><name><surname>Liu</surname><given-names>CG</given-names></name><name><surname>Sevignani</surname><given-names>C</given-names></name><name><surname>Ferracin</surname><given-names>M</given-names></name><name><surname>Felli</surname><given-names>N</given-names></name><name><surname>Dumitru</surname><given-names>CD</given-names></name><etal></etal></person-group><article-title>MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias</article-title><source>Proc Natl Acad Sci U S A</source><year>2004</year><volume>101</volume><fpage>11755</fpage><lpage>11760</lpage><pub-id pub-id-type="pmid">15284443</pub-id></element-citation></ref><ref id="R31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hummel</surname><given-names>M</given-names></name><name><surname>Bentink</surname><given-names>S</given-names></name><name><surname>Berger</surname><given-names>H</given-names></name><name><surname>Klapper</surname><given-names>W</given-names></name><name><surname>Wessendorf</surname><given-names>S</given-names></name><name><surname>Barth</surname><given-names>TF</given-names></name><etal></etal></person-group><article-title>Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe. A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling</article-title><source>N Engl J Med</source><year>2006</year><volume>354</volume><fpage>2419</fpage><lpage>2430</lpage><pub-id pub-id-type="pmid">16760442</pub-id></element-citation></ref><ref id="R32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dave</surname><given-names>SS</given-names></name><name><surname>Fu</surname><given-names>K</given-names></name><name><surname>Wright</surname><given-names>GW</given-names></name><name><surname>Lam</surname><given-names>LT</given-names></name><name><surname>Kluin</surname><given-names>P</given-names></name><name><surname>Boerma</surname><given-names>EJ</given-names></name><etal></etal></person-group><article-title>Lymphoma/Leukemia Molecular Profiling Project. Molecular diagnosis of Burkitt’s lymphoma</article-title><source>N Engl J Med</source><year>2006</year><volume>354</volume><fpage>2431</fpage><lpage>2442</lpage><pub-id pub-id-type="pmid">16760443</pub-id></element-citation></ref><ref id="R33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kawasaki</surname><given-names>C</given-names></name><name><surname>Ohshim</surname><given-names>K</given-names></name><name><surname>Suzumiya</surname><given-names>J</given-names></name><name><surname>Kanda</surname><given-names>M</given-names></name><name><surname>Tsuchiya</surname><given-names>T</given-names></name><name><surname>Tamura</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Rearrangements of bcl-1, bcl-2, bcl-6, and c-myc in diffuse large B-cell lymphomas</article-title><source>Leuk Lymphoma</source><year>2001</year><volume>42</volume><fpage>1099</fpage><lpage>1106</lpage><pub-id pub-id-type="pmid">11697627</pub-id></element-citation></ref><ref id="R34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Akasaka</surname><given-names>T</given-names></name><name><surname>Akasaka</surname><given-names>H</given-names></name><name><surname>Ueda</surname><given-names>C</given-names></name><name><surname>Kanda</surname><given-names>M</given-names></name><name><surname>Tsuchiya</surname><given-names>T</given-names></name><name><surname>Tamura</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Molecular and clinical features of non-Burkitt’s, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene</article-title><source>J Clin Oncol</source><year>2000</year><volume>18</volume><fpage>510</fpage><lpage>518</lpage><pub-id pub-id-type="pmid">10653866</pub-id></element-citation></ref><ref id="R35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miles</surname><given-names>R</given-names></name><name><surname>Raphael</surname><given-names>M</given-names></name><name><surname>McCarthy</surname><given-names>K</given-names></name><name><surname>Wotherspoon</surname><given-names>A</given-names></name><name><surname>Lones</surname><given-names>M</given-names></name><name><surname>Cairo</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Diffuse large B-cell lymphomas in pediatric patients demonstrate a marked predominance of germinal center cell phenotype</article-title><source>Ann Oncol</source><year>2005</year><volume>16</volume><fpage>v 61</fpage><comment>abstract</comment></element-citation></ref><ref id="R36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oschlies</surname><given-names>I</given-names></name><name><surname>Klapper</surname><given-names>W</given-names></name><name><surname>Zimmermann</surname><given-names>M</given-names></name><name><surname>Krams</surname><given-names>M</given-names></name><name><surname>Wacker</surname><given-names>HH</given-names></name><name><surname>Burkhardt</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas: a clinicopathologic analysis of cases included in the German BFM (Berlin-Frankfurt-Munster) Multicenter Trial</article-title><source>Blood</source><year>2006</year><volume>107</volume><fpage>4047</fpage><lpage>4052</lpage><pub-id pub-id-type="pmid">16424389</pub-id></element-citation></ref><ref id="R37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rosenwald</surname><given-names>A</given-names></name><name><surname>Wright</surname><given-names>G</given-names></name><name><surname>Chan</surname><given-names>WC</given-names></name><name><surname>Connors</surname><given-names>JM</given-names></name><name><surname>Campo</surname><given-names>E</given-names></name><name><surname>Fisher</surname><given-names>RI</given-names></name><etal></etal></person-group><article-title>The use of molecular profiling to predict survival after chemotherapy for diffuse large B-cell lymphoma</article-title><source>N Engl J Med</source><year>2002</year><volume>346</volume><fpage>1937</fpage><lpage>1947</lpage><pub-id pub-id-type="pmid">12075054</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><title>Distribution of cytogenetic abnormalities in FAB/LMB 96 Study stratified by histological subtypes Burkitt Lymphoma (BL), Burkitt Like Lymphoma (BLL) and Diffuse Large B-Cell Lymphoma (DLBCL)</title><p>R8q24, dup(1q), del(6q), der(11q), +12, ploidy and complexity are helpful in the discrimination between BL and DLBCL. BLL exhibit an intermediary pattern.</p></caption><graphic xlink:href="nihms107551f1"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><title>Probability of EFS by Kaplan-Meier method in children with B-NHL treated on FAB/LMB 96 on the whole population (N=238)</title><p>Figure 2A: EFS with and without rearranged 8q24 cytogenetic abnormality</p><p>Figure 2B: EFS with and without del(13q) cytogenetic abnormality</p><p>Figure 2C: EFS with and without +7q cytogenetic abnormality</p><p>Figure 2D: EFS with and without a complex karyotype (>3 cytogenetic abnormalities)</p></caption><graphic xlink:href="nihms107551f2"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><title>Probability of EFS by Kaplen-Meier method in children with B-NHL treated on FAB/LMB 96 according to the main morphologic entities BL (N=182) and DLBCL (N=30)</title><p>Figure 3A: EFS with and without rearranged 8q24 cytogenetic abnormality</p><p>Figure 3B: EFS with and without del(13q) cytogenetic abnormality</p><p>Figure 3C: EFS with and without +7q cytogenetic abnormality</p><p>Figure 3D: EFS with and without a complex karyotype (>3 cytogenetic abnormalities)</p><p>While del(13q), +7q and the complexity altered the prognosis of BL and DLBCL in the same proportion, the adverse effect of R8q24 is only detected in DLBCL.</p></caption><graphic xlink:href="nihms107551f3"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><p>Initial patient characteristics of the 238 cases with cytogenetics Comparison with the other cases without cytogenetics of FAB/LMB96</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" colspan="2" valign="bottom" rowspan="1">With cytogenetics (N=238)</th><th align="center" colspan="2" valign="bottom" rowspan="1">Without cytogenetics (N=780)</th><th align="center" valign="bottom" rowspan="1" colspan="1">p<xref rid="TFN4" ref-type="table-fn">*</xref></th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1"><bold>M/F Sex ratio</bold></td><td align="center" colspan="2" rowspan="1">180/58 (3.1)</td><td align="center" colspan="2" rowspan="1">603/177 (3.4)</td><td align="center" rowspan="1" colspan="1">0.59</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Median age</bold>, years [range]</td><td align="center" colspan="2" rowspan="1">9.1 [2-20]</td><td align="center" colspan="2" rowspan="1">10.1 [1-20]</td><td align="center" rowspan="1" colspan="1">0.03<xref rid="TFN5" ref-type="table-fn">◦</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Therapeutic group</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.0001</td></tr><tr><td align="left" rowspan="1" colspan="1"> A</td><td align="center" rowspan="1" colspan="1">11</td><td align="left" rowspan="1" colspan="1">(5%)</td><td align="left" rowspan="1" colspan="1">119</td><td align="left" rowspan="1" colspan="1">(15%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> B</td><td align="center" rowspan="1" colspan="1">132</td><td align="left" rowspan="1" colspan="1">(55%)</td><td align="left" rowspan="1" colspan="1">550</td><td align="left" rowspan="1" colspan="1">(71%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> C</td><td align="center" rowspan="1" colspan="1">95</td><td align="left" rowspan="1" colspan="1">(40%)</td><td align="left" rowspan="1" colspan="1">111</td><td align="left" rowspan="1" colspan="1">(14%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Stage</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.0001</td></tr><tr><td align="left" rowspan="1" colspan="1"> I</td><td align="center" rowspan="1" colspan="1">11</td><td align="left" rowspan="1" colspan="1">(5%)</td><td align="left" rowspan="1" colspan="1">104</td><td align="left" rowspan="1" colspan="1">(13%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> II</td><td align="center" rowspan="1" colspan="1">26</td><td align="left" rowspan="1" colspan="1">(11%)</td><td align="left" rowspan="1" colspan="1">187</td><td align="left" rowspan="1" colspan="1">(24%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> III</td><td align="center" rowspan="1" colspan="1">88</td><td align="left" rowspan="1" colspan="1">(37%)</td><td align="left" rowspan="1" colspan="1">358</td><td align="left" rowspan="1" colspan="1">(46%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> IV</td><td align="center" rowspan="1" colspan="1">33</td><td align="left" rowspan="1" colspan="1">(14%)</td><td align="left" rowspan="1" colspan="1">61</td><td align="left" rowspan="1" colspan="1">(8%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Leukemia</td><td align="center" rowspan="1" colspan="1">80</td><td align="left" rowspan="1" colspan="1">(34%)</td><td align="left" rowspan="1" colspan="1">70</td><td align="left" rowspan="1" colspan="1">(9%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>LDH</bold> > 2N</td><td align="center" rowspan="1" colspan="1">167</td><td align="left" rowspan="1" colspan="1">(71%)</td><td align="left" rowspan="1" colspan="1">244</td><td align="left" rowspan="1" colspan="1">(33%)</td><td align="center" rowspan="1" colspan="1">0.0001</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>CNS disease</bold></td><td align="center" rowspan="1" colspan="1">42</td><td align="left" rowspan="1" colspan="1">(18%)</td><td align="left" rowspan="1" colspan="1">65</td><td align="left" rowspan="1" colspan="1">(8%)</td><td align="center" rowspan="1" colspan="1">0.0001</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>COP response</bold> <20%</td><td align="center" rowspan="1" colspan="1">9/227</td><td align="left" rowspan="1" colspan="1">(4%)</td><td align="left" rowspan="1" colspan="1">31/658</td><td align="left" rowspan="1" colspan="1">(5%)</td><td align="center" rowspan="1" colspan="1">0.64</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Morphologic group</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.0001</td></tr><tr><td align="left" rowspan="1" colspan="1"> BL</td><td align="center" rowspan="1" colspan="1">182</td><td align="left" rowspan="1" colspan="1">(76%)</td><td align="left" rowspan="1" colspan="1">468</td><td align="left" rowspan="1" colspan="1">(60%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> BLL</td><td align="center" rowspan="1" colspan="1">18</td><td align="left" rowspan="1" colspan="1">(8%)</td><td align="left" rowspan="1" colspan="1">58</td><td align="left" rowspan="1" colspan="1">(7%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> DLBCL</td><td align="center" rowspan="1" colspan="1">30</td><td align="left" rowspan="1" colspan="1">(13%)</td><td align="left" rowspan="1" colspan="1">208</td><td align="left" rowspan="1" colspan="1">(26%)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Not sub classified</td><td align="center" rowspan="1" colspan="1">8</td><td align="left" rowspan="1" colspan="1">(3%)</td><td align="left" rowspan="1" colspan="1">46</td><td align="left" rowspan="1" colspan="1">(6%)</td><td align="center" rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p>M/F : Male/Female</p></fn><fn id="TFN2"><p>CNS : central nervous system</p></fn><fn id="TFN3"><p>BL : Burkitt lymphoma, BLL : Burkitt-like lymphoma, DLBCL : diffuse large B-cell lymphoma</p></fn><fn id="TFN4"><label>*</label><p>chi-square test except for</p></fn><fn id="TFN5"><label>◦</label><p>Kruskal-Wallis test</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><p>Prognostic significance of individual cytogenetic abnormalities (analysis of each abnormality separately)</p></caption><table frame="box" rules="all"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" colspan="3" rowspan="1">Whole population</th><th align="center" colspan="3" rowspan="1">Burkitt lymphoma</th><th align="center" colspan="2" rowspan="1">DLBCL</th></tr><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" colspan="3" rowspan="1">EFS (43 events / 238 patients)</th><th align="center" colspan="3" rowspan="1">EFS (30 events / 182 patients)</th><th align="center" colspan="2" rowspan="1">EFS (5 events / 30 patients)</th></tr><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" valign="top" rowspan="1" colspan="1">Event / Patient</th><th align="center" valign="top" rowspan="1" colspan="1">HR [IC95%]</th><th align="center" valign="top" rowspan="1" colspan="1">p</th><th align="center" valign="top" rowspan="1" colspan="1">Event / Patient</th><th align="center" valign="top" rowspan="1" colspan="1">HR [IC95%]</th><th align="center" valign="top" rowspan="1" colspan="1">p</th><th align="center" valign="top" rowspan="1" colspan="1">Event / Patient</th><th align="center" valign="top" rowspan="1" colspan="1">p</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1"><bold>R8q24</bold></td><td align="center" rowspan="1" colspan="1">41 / 201</td><td align="center" rowspan="1" colspan="1">5.4 [1.2-25]</td><td align="center" rowspan="1" colspan="1">0.03<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">28 / 169</td><td align="center" rowspan="1" colspan="1">1.2 [0.26-5.2]</td><td align="center" rowspan="1" colspan="1">0.84<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">5 / 10</td><td align="center" rowspan="1" colspan="1">0.0004<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"> N8q24</td><td align="center" rowspan="1" colspan="1">2 / 37</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> R8q24 alone</td><td align="center" rowspan="1" colspan="1">10 / 62</td><td align="center" rowspan="1" colspan="1">4.0 [0.75-21]</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> R8q24 associated</td><td align="center" rowspan="1" colspan="1">31 / 139</td><td align="center" rowspan="1" colspan="1">5.7 [1.2-26]</td><td align="center" rowspan="1" colspan="1">0.06<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>del(13q)</bold></td><td align="center" rowspan="1" colspan="1">12 / 33</td><td align="center" rowspan="1" colspan="1">4.3 [2.0-9.1]</td><td align="center" rowspan="1" colspan="1">0.0002<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">8 / 26</td><td align="center" rowspan="1" colspan="1">4.8 [1.9-12]</td><td align="center" rowspan="1" colspan="1">0.001<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">1 / 3</td><td align="center" rowspan="1" colspan="1">0.31<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>der(3q)</bold></td><td align="center" rowspan="1" colspan="1">5 / 13</td><td align="center" rowspan="1" colspan="1">3.1 [1.1-8.4]</td><td align="center" rowspan="1" colspan="1">0.03<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">2 / 8</td><td align="center" rowspan="1" colspan="1">2.8 [0.60-12.8]</td><td align="center" rowspan="1" colspan="1">0.19<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">2 / 4</td><td align="center" rowspan="1" colspan="1">0.02<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>+7q</bold></td><td align="center" rowspan="1" colspan="1">10 / 36</td><td align="center" rowspan="1" colspan="1">2.8 [1.4-5.9]</td><td align="center" rowspan="1" colspan="1">0.005<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">6 / 25</td><td align="center" rowspan="1" colspan="1">2.6 [1.01-6.5]</td><td align="center" rowspan="1" colspan="1">0.047<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">2 / 8</td><td align="center" rowspan="1" colspan="1">0.44<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>complexity</bold></td><td align="center" rowspan="1" colspan="1">24 /87</td><td align="center" rowspan="1" colspan="1">3.2 [1.7-6.1]</td><td align="center" rowspan="1" colspan="1">0.0005<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">13 / 50</td><td align="center" rowspan="1" colspan="1">2.5 [1.2-5.2]</td><td align="center" rowspan="1" colspan="1">0.02<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">5 / 24</td><td align="center" rowspan="1" colspan="1">0.24<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>aneuploidy</bold></td><td align="center" rowspan="1" colspan="1">21 / 86</td><td align="center" rowspan="1" colspan="1">2.1 [1.1-4.0]</td><td align="center" rowspan="1" colspan="1">0.02<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">13 / 49</td><td align="center" rowspan="1" colspan="1">2.5 [1.2-5.4]</td><td align="center" rowspan="1" colspan="1">0.02<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">3 / 24</td><td align="center" rowspan="1" colspan="1">0.19<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">+1q</td><td align="center" rowspan="1" colspan="1">8 / 65</td><td align="center" rowspan="1" colspan="1">0.53 [0.24-1.2]</td><td align="center" rowspan="1" colspan="1">0.11<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">4 / 52</td><td align="center" rowspan="1" colspan="1">0.37 [0.13-1.1]</td><td align="center" rowspan="1" colspan="1">0.065<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">1 / 4</td><td align="center" rowspan="1" colspan="1">0.63<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">del(6q)</td><td align="center" rowspan="1" colspan="1">6 / 33</td><td align="center" rowspan="1" colspan="1">0.97 [0.35-2.6]</td><td align="center" rowspan="1" colspan="1">0.95<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">3 / 18</td><td align="center" rowspan="1" colspan="1">1.1 [0.32-3.7]</td><td align="center" rowspan="1" colspan="1">0.90<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">3 / 13</td><td align="center" rowspan="1" colspan="1">0.38<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">der(9p)</td><td align="center" rowspan="1" colspan="1">0 / 7</td><td align="center" rowspan="1" colspan="1">/</td><td align="center" rowspan="1" colspan="1">0.37<xref rid="TFN8" ref-type="table-fn">◦</xref></td><td align="center" rowspan="1" colspan="1">0 / 5</td><td align="center" rowspan="1" colspan="1">/</td><td align="center" rowspan="1" colspan="1">0.48<xref rid="TFN8" ref-type="table-fn">◦</xref></td><td align="center" rowspan="1" colspan="1">0 / 2</td><td align="center" rowspan="1" colspan="1">0.53<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">der(11q)</td><td align="center" rowspan="1" colspan="1">3 / 19</td><td align="center" rowspan="1" colspan="1">0.96 [0.28-3.3]</td><td align="center" rowspan="1" colspan="1">0.95<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">0 / 8</td><td align="center" rowspan="1" colspan="1">/</td><td align="center" rowspan="1" colspan="1">0.23<xref rid="TFN8" ref-type="table-fn">◦</xref></td><td align="center" rowspan="1" colspan="1">2 / 8</td><td align="center" rowspan="1" colspan="1">0.43<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">+12q</td><td align="center" rowspan="1" colspan="1">1 / 16</td><td align="center" rowspan="1" colspan="1">0.24 [0.03-1.9]</td><td align="center" rowspan="1" colspan="1">0.18<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">0 / 6</td><td align="center" rowspan="1" colspan="1">/</td><td align="center" rowspan="1" colspan="1">0.28<xref rid="TFN8" ref-type="table-fn">◦</xref></td><td align="center" rowspan="1" colspan="1">0 / 7</td><td align="center" rowspan="1" colspan="1">0.20<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">del(17p)</td><td align="center" rowspan="1" colspan="1">6 / 21</td><td align="center" rowspan="1" colspan="1">1.4 [0.56-3.7]</td><td align="center" rowspan="1" colspan="1">0.45<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">4 / 11</td><td align="center" rowspan="1" colspan="1">1.8 [0.63-5.4]</td><td align="center" rowspan="1" colspan="1">0.27<xref rid="TFN7" ref-type="table-fn">$</xref></td><td align="center" rowspan="1" colspan="1">1 / 7</td><td align="center" rowspan="1" colspan="1">0.85<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr><tr><td align="left" rowspan="1" colspan="1">der(18q)</td><td align="center" rowspan="1" colspan="1">3 / 10</td><td align="center" rowspan="1" colspan="1">2.1 [0.57-7.8]</td><td align="center" rowspan="1" colspan="1">0.27<xref rid="TFN6" ref-type="table-fn">*</xref></td><td align="center" rowspan="1" colspan="1">0 / 4</td><td align="center" rowspan="1" colspan="1">/</td><td align="center" rowspan="1" colspan="1">0.52<xref rid="TFN8" ref-type="table-fn">◦</xref></td><td align="center" rowspan="1" colspan="1">1 / 4</td><td align="center" rowspan="1" colspan="1">0.63<xref rid="TFN9" ref-type="table-fn">£</xref></td></tr></tbody></table><table-wrap-foot><fn id="TFN6"><label>*</label><p>Adjusted on
<list list-type="simple" id="L1"><list-item><p>- national cooperative group (SFOP vs CCG vs UKCCSG)</p></list-item><list-item><p>- therapeutic stratification group (C vs A / B)</p></list-item><list-item><p>- pathology (DLBCL vs BL / BLL / not sub classified)</p></list-item><list-item><p>- LDH level (>2N vs <=2N)</p></list-item><list-item><p>- CNS disease (yes vs no)</p></list-item><list-item><p>- primary mediastinal localisation (yes vs no)</p></list-item></list></p></fn><fn id="TFN7"><label>$</label><p>Adjusted on
<list list-type="simple" id="L2"><list-item><p>- national cooperative group (SFOP vs CCG vs UKCCSG)</p></list-item><list-item><p>- therapeutic stratification group (C vs A / B)</p></list-item><list-item><p>- LDH level (>2N vs <=2N)</p></list-item><list-item><p>- CNS disease (yes vs no)</p></list-item></list></p></fn><fn id="TFN8"><label>◦</label><p>Logrank test adjusted on LDH level and CNS disease</p></fn><fn id="TFN9"><label>£</label><p>Logrank test without any adjustment (due to the small number of events)</p></fn><fn id="TFN10"><p>HR : hazard ratio</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Psychologie/explor/BernheimV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000217 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000217 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Psychologie
|area= BernheimV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:2988438
|texte= Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:19020548" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a BernheimV1
| This area was generated with Dilib version V0.6.33. |  |