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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: Impact of tyrosine kinase inhibitor and minimal residual disease</title><author><name sortKey="Bachanova, Veronika" sort="Bachanova, Veronika" uniqKey="Bachanova V" first="Veronika" last="Bachanova">Veronika Bachanova</name><affiliation><nlm:aff id="A1">Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN</nlm:aff></affiliation></author><author><name sortKey="Marks, David I" sort="Marks, David I" uniqKey="Marks D" first="David I." last="Marks">David I. Marks</name><affiliation><nlm:aff id="A2">Bristol Adult BMT Unit, Bristol Children’s Hospital, Bristol, UNITED KINGDOM</nlm:aff></affiliation></author><author><name sortKey="Zhang, Mei Jie" sort="Zhang, Mei Jie" uniqKey="Zhang M" first="Mei-Jie" last="Zhang">Mei-Jie Zhang</name><affiliation><nlm:aff id="A3">Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="Wang, Hailin" sort="Wang, Hailin" uniqKey="Wang H" first="Hailin" last="Wang">Hailin Wang</name><affiliation><nlm:aff id="A3">Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="De Lima, Marcos" sort="De Lima, Marcos" uniqKey="De Lima M" first="Marcos" last="De Lima">Marcos De Lima</name><affiliation><nlm:aff id="A4">Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH</nlm:aff></affiliation></author><author><name sortKey="Aljurf, Mahmoud D" sort="Aljurf, Mahmoud D" uniqKey="Aljurf M" first="Mahmoud D." last="Aljurf">Mahmoud D. Aljurf</name><affiliation><nlm:aff id="A5">King Faisal Specialist Hospital and Research Center, Riyadh, SAUDI ARABIA</nlm:aff></affiliation></author><author><name sortKey="Arellano, Martha" sort="Arellano, Martha" uniqKey="Arellano M" first="Martha" last="Arellano">Martha Arellano</name><affiliation><nlm:aff id="A6">Winship Cancer Institute, Emory University, Atlanta, GA</nlm:aff></affiliation></author><author><name sortKey="Artz, Andrew S" sort="Artz, Andrew S" uniqKey="Artz A" first="Andrew S." last="Artz">Andrew S. Artz</name><affiliation><nlm:aff id="A7">University of Chicago Medicine, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Bacher, Ulrike" sort="Bacher, Ulrike" uniqKey="Bacher U" first="Ulrike" last="Bacher">Ulrike Bacher</name><affiliation><nlm:aff id="A8">Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, GERMANY</nlm:aff></affiliation></author><author><name sortKey="Cahn, Jean Yves" sort="Cahn, Jean Yves" uniqKey="Cahn J" first="Jean-Yves" last="Cahn">Jean-Yves Cahn</name><affiliation><nlm:aff id="A9">Department of Hematology, University Hospital, Grenoble, FRANCE</nlm:aff></affiliation></author><author><name sortKey="Chen, Yi Bin" sort="Chen, Yi Bin" uniqKey="Chen Y" first="Yi-Bin" last="Chen">Yi-Bin Chen</name><affiliation><nlm:aff id="A10">Massachusetts General Hospital, Boston, MA</nlm:aff></affiliation></author><author><name sortKey="Copelan, Edward A" sort="Copelan, Edward A" uniqKey="Copelan E" first="Edward A." last="Copelan">Edward A. Copelan</name><affiliation><nlm:aff id="A11">Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC</nlm:aff></affiliation></author><author><name sortKey="Drobyski, William R" sort="Drobyski, William R" uniqKey="Drobyski W" first="William R." last="Drobyski">William R. Drobyski</name><affiliation><nlm:aff id="A12">Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="Gale, Robert Peter" sort="Gale, Robert Peter" uniqKey="Gale R" first="Robert Peter" last="Gale">Robert Peter Gale</name><affiliation><nlm:aff id="A13">Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UNITED KINGDOM</nlm:aff></affiliation></author><author><name sortKey="Greer, John P" sort="Greer, John P" uniqKey="Greer J" first="John P" last="Greer">John P. Greer</name><affiliation><nlm:aff id="A14">Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Gupta, Vikas" sort="Gupta, Vikas" uniqKey="Gupta V" first="Vikas" last="Gupta">Vikas Gupta</name><affiliation><nlm:aff id="A15">Princess Margaret Hospital, Toronto, ON, CANADA</nlm:aff></affiliation></author><author><name sortKey="Hale, Gregory A" sort="Hale, Gregory A" uniqKey="Hale G" first="Gregory A." last="Hale">Gregory A. Hale</name><affiliation><nlm:aff id="A16">All Children’s Hospital, St. Petersburg, FL</nlm:aff></affiliation></author><author><name sortKey="Kebriaei, Partow" sort="Kebriaei, Partow" uniqKey="Kebriaei P" first="Partow" last="Kebriaei">Partow Kebriaei</name><affiliation><nlm:aff id="A17">Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Lazarus, Hillard M" sort="Lazarus, Hillard M" uniqKey="Lazarus H" first="Hillard M." last="Lazarus">Hillard M. Lazarus</name><affiliation><nlm:aff id="A4">Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH</nlm:aff></affiliation></author><author><name sortKey="Lewis, Ian D" sort="Lewis, Ian D" uniqKey="Lewis I" first="Ian D." last="Lewis">Ian D. Lewis</name><affiliation><nlm:aff id="A18">Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, AUSTRALIA</nlm:aff></affiliation></author><author><name sortKey="Lewis, Victor A" sort="Lewis, Victor A" uniqKey="Lewis V" first="Victor A." last="Lewis">Victor A. Lewis</name><affiliation><nlm:aff id="A19">Alberta Children’s Hospital, Calgary, AB, CANADA</nlm:aff></affiliation></author><author><name sortKey="Liesveld, Jane L" sort="Liesveld, Jane L" uniqKey="Liesveld J" first="Jane L." last="Liesveld">Jane L. Liesveld</name><affiliation><nlm:aff id="A20">Strong Memorial Hospital, University of Rochester Medical Center; Rochester, NY</nlm:aff></affiliation></author><author><name sortKey="Litzow, Mark R" sort="Litzow, Mark R" uniqKey="Litzow M" first="Mark R." last="Litzow">Mark R. Litzow</name><affiliation><nlm:aff id="A21">Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN</nlm:aff></affiliation></author><author><name sortKey="Loren, Alison W" sort="Loren, Alison W" uniqKey="Loren A" first="Alison W." last="Loren">Alison W. Loren</name><affiliation><nlm:aff id="A22">Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA</nlm:aff></affiliation></author><author><name sortKey="Miller, Alan M" sort="Miller, Alan M" uniqKey="Miller A" first="Alan M." last="Miller">Alan M. Miller</name><affiliation><nlm:aff id="A23">Baylor University Medical Center, Dallas, TX</nlm:aff></affiliation></author><author><name sortKey="Norkin, Maxim" sort="Norkin, Maxim" uniqKey="Norkin M" first="Maxim" last="Norkin">Maxim Norkin</name><affiliation><nlm:aff id="A24">Shands HealthCare and University of Florida, Gainesville, FL</nlm:aff></affiliation></author><author><name sortKey="Oran, Betul" sort="Oran, Betul" uniqKey="Oran B" first="Betul" last="Oran">Betul Oran</name><affiliation><nlm:aff id="A17">Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Pidala, Joseph" sort="Pidala, Joseph" uniqKey="Pidala J" first="Joseph" last="Pidala">Joseph Pidala</name><affiliation><nlm:aff id="A25">Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL</nlm:aff></affiliation></author><author><name sortKey="Rowe, Jacob M" sort="Rowe, Jacob M" uniqKey="Rowe J" first="Jacob M." last="Rowe">Jacob M. Rowe</name><affiliation><nlm:aff id="A26">Department of Hematology, Rambam Medical Center, Haifa, ISRAEL</nlm:aff></affiliation></author><author><name sortKey="Savani, Bipin N" sort="Savani, Bipin N" uniqKey="Savani B" first="Bipin N." last="Savani">Bipin N. Savani</name><affiliation><nlm:aff id="A14">Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Saber, Wael" sort="Saber, Wael" uniqKey="Saber W" first="Wael" last="Saber">Wael Saber</name><affiliation><nlm:aff id="A3">Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="Vij, Ravi" sort="Vij, Ravi" uniqKey="Vij R" first="Ravi" last="Vij">Ravi Vij</name><affiliation><nlm:aff id="A27">Barnes Jewish Hospital, Washington University School of Medicine, St. Louis, MO</nlm:aff></affiliation></author><author><name sortKey="Waller, Edmund K" sort="Waller, Edmund K" uniqKey="Waller E" first="Edmund K." last="Waller">Edmund K. Waller</name><affiliation><nlm:aff id="A28">Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA</nlm:aff></affiliation></author><author><name sortKey="Wiernik, Peter H" sort="Wiernik, Peter H" uniqKey="Wiernik P" first="Peter H." last="Wiernik">Peter H. Wiernik</name><affiliation><nlm:aff id="A29">Our Lady of Mercy Medical Center, Bronx, NY</nlm:aff></affiliation></author><author><name sortKey="Weisdorf, Daniel J" sort="Weisdorf, Daniel J" uniqKey="Weisdorf D" first="Daniel J." last="Weisdorf">Daniel J. Weisdorf</name><affiliation><nlm:aff id="A1">Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23989431</idno><idno type="pmc">3951192</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951192</idno><idno type="RBID">PMC:3951192</idno><idno type="doi">10.1038/leu.2013.253</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002D96</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002D96</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: Impact of tyrosine kinase inhibitor and minimal residual disease</title><author><name sortKey="Bachanova, Veronika" sort="Bachanova, Veronika" uniqKey="Bachanova V" first="Veronika" last="Bachanova">Veronika Bachanova</name><affiliation><nlm:aff id="A1">Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN</nlm:aff></affiliation></author><author><name sortKey="Marks, David I" sort="Marks, David I" uniqKey="Marks D" first="David I." last="Marks">David I. Marks</name><affiliation><nlm:aff id="A2">Bristol Adult BMT Unit, Bristol Children’s Hospital, Bristol, UNITED KINGDOM</nlm:aff></affiliation></author><author><name sortKey="Zhang, Mei Jie" sort="Zhang, Mei Jie" uniqKey="Zhang M" first="Mei-Jie" last="Zhang">Mei-Jie Zhang</name><affiliation><nlm:aff id="A3">Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="Wang, Hailin" sort="Wang, Hailin" uniqKey="Wang H" first="Hailin" last="Wang">Hailin Wang</name><affiliation><nlm:aff id="A3">Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="De Lima, Marcos" sort="De Lima, Marcos" uniqKey="De Lima M" first="Marcos" last="De Lima">Marcos De Lima</name><affiliation><nlm:aff id="A4">Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH</nlm:aff></affiliation></author><author><name sortKey="Aljurf, Mahmoud D" sort="Aljurf, Mahmoud D" uniqKey="Aljurf M" first="Mahmoud D." last="Aljurf">Mahmoud D. Aljurf</name><affiliation><nlm:aff id="A5">King Faisal Specialist Hospital and Research Center, Riyadh, SAUDI ARABIA</nlm:aff></affiliation></author><author><name sortKey="Arellano, Martha" sort="Arellano, Martha" uniqKey="Arellano M" first="Martha" last="Arellano">Martha Arellano</name><affiliation><nlm:aff id="A6">Winship Cancer Institute, Emory University, Atlanta, GA</nlm:aff></affiliation></author><author><name sortKey="Artz, Andrew S" sort="Artz, Andrew S" uniqKey="Artz A" first="Andrew S." last="Artz">Andrew S. Artz</name><affiliation><nlm:aff id="A7">University of Chicago Medicine, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Bacher, Ulrike" sort="Bacher, Ulrike" uniqKey="Bacher U" first="Ulrike" last="Bacher">Ulrike Bacher</name><affiliation><nlm:aff id="A8">Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, GERMANY</nlm:aff></affiliation></author><author><name sortKey="Cahn, Jean Yves" sort="Cahn, Jean Yves" uniqKey="Cahn J" first="Jean-Yves" last="Cahn">Jean-Yves Cahn</name><affiliation><nlm:aff id="A9">Department of Hematology, University Hospital, Grenoble, FRANCE</nlm:aff></affiliation></author><author><name sortKey="Chen, Yi Bin" sort="Chen, Yi Bin" uniqKey="Chen Y" first="Yi-Bin" last="Chen">Yi-Bin Chen</name><affiliation><nlm:aff id="A10">Massachusetts General Hospital, Boston, MA</nlm:aff></affiliation></author><author><name sortKey="Copelan, Edward A" sort="Copelan, Edward A" uniqKey="Copelan E" first="Edward A." last="Copelan">Edward A. Copelan</name><affiliation><nlm:aff id="A11">Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC</nlm:aff></affiliation></author><author><name sortKey="Drobyski, William R" sort="Drobyski, William R" uniqKey="Drobyski W" first="William R." last="Drobyski">William R. Drobyski</name><affiliation><nlm:aff id="A12">Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="Gale, Robert Peter" sort="Gale, Robert Peter" uniqKey="Gale R" first="Robert Peter" last="Gale">Robert Peter Gale</name><affiliation><nlm:aff id="A13">Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UNITED KINGDOM</nlm:aff></affiliation></author><author><name sortKey="Greer, John P" sort="Greer, John P" uniqKey="Greer J" first="John P" last="Greer">John P. Greer</name><affiliation><nlm:aff id="A14">Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Gupta, Vikas" sort="Gupta, Vikas" uniqKey="Gupta V" first="Vikas" last="Gupta">Vikas Gupta</name><affiliation><nlm:aff id="A15">Princess Margaret Hospital, Toronto, ON, CANADA</nlm:aff></affiliation></author><author><name sortKey="Hale, Gregory A" sort="Hale, Gregory A" uniqKey="Hale G" first="Gregory A." last="Hale">Gregory A. Hale</name><affiliation><nlm:aff id="A16">All Children’s Hospital, St. Petersburg, FL</nlm:aff></affiliation></author><author><name sortKey="Kebriaei, Partow" sort="Kebriaei, Partow" uniqKey="Kebriaei P" first="Partow" last="Kebriaei">Partow Kebriaei</name><affiliation><nlm:aff id="A17">Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Lazarus, Hillard M" sort="Lazarus, Hillard M" uniqKey="Lazarus H" first="Hillard M." last="Lazarus">Hillard M. Lazarus</name><affiliation><nlm:aff id="A4">Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH</nlm:aff></affiliation></author><author><name sortKey="Lewis, Ian D" sort="Lewis, Ian D" uniqKey="Lewis I" first="Ian D." last="Lewis">Ian D. Lewis</name><affiliation><nlm:aff id="A18">Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, AUSTRALIA</nlm:aff></affiliation></author><author><name sortKey="Lewis, Victor A" sort="Lewis, Victor A" uniqKey="Lewis V" first="Victor A." last="Lewis">Victor A. Lewis</name><affiliation><nlm:aff id="A19">Alberta Children’s Hospital, Calgary, AB, CANADA</nlm:aff></affiliation></author><author><name sortKey="Liesveld, Jane L" sort="Liesveld, Jane L" uniqKey="Liesveld J" first="Jane L." last="Liesveld">Jane L. Liesveld</name><affiliation><nlm:aff id="A20">Strong Memorial Hospital, University of Rochester Medical Center; Rochester, NY</nlm:aff></affiliation></author><author><name sortKey="Litzow, Mark R" sort="Litzow, Mark R" uniqKey="Litzow M" first="Mark R." last="Litzow">Mark R. Litzow</name><affiliation><nlm:aff id="A21">Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN</nlm:aff></affiliation></author><author><name sortKey="Loren, Alison W" sort="Loren, Alison W" uniqKey="Loren A" first="Alison W." last="Loren">Alison W. Loren</name><affiliation><nlm:aff id="A22">Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA</nlm:aff></affiliation></author><author><name sortKey="Miller, Alan M" sort="Miller, Alan M" uniqKey="Miller A" first="Alan M." last="Miller">Alan M. Miller</name><affiliation><nlm:aff id="A23">Baylor University Medical Center, Dallas, TX</nlm:aff></affiliation></author><author><name sortKey="Norkin, Maxim" sort="Norkin, Maxim" uniqKey="Norkin M" first="Maxim" last="Norkin">Maxim Norkin</name><affiliation><nlm:aff id="A24">Shands HealthCare and University of Florida, Gainesville, FL</nlm:aff></affiliation></author><author><name sortKey="Oran, Betul" sort="Oran, Betul" uniqKey="Oran B" first="Betul" last="Oran">Betul Oran</name><affiliation><nlm:aff id="A17">Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX</nlm:aff></affiliation></author><author><name sortKey="Pidala, Joseph" sort="Pidala, Joseph" uniqKey="Pidala J" first="Joseph" last="Pidala">Joseph Pidala</name><affiliation><nlm:aff id="A25">Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL</nlm:aff></affiliation></author><author><name sortKey="Rowe, Jacob M" sort="Rowe, Jacob M" uniqKey="Rowe J" first="Jacob M." last="Rowe">Jacob M. Rowe</name><affiliation><nlm:aff id="A26">Department of Hematology, Rambam Medical Center, Haifa, ISRAEL</nlm:aff></affiliation></author><author><name sortKey="Savani, Bipin N" sort="Savani, Bipin N" uniqKey="Savani B" first="Bipin N." last="Savani">Bipin N. Savani</name><affiliation><nlm:aff id="A14">Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Saber, Wael" sort="Saber, Wael" uniqKey="Saber W" first="Wael" last="Saber">Wael Saber</name><affiliation><nlm:aff id="A3">Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI</nlm:aff></affiliation></author><author><name sortKey="Vij, Ravi" sort="Vij, Ravi" uniqKey="Vij R" first="Ravi" last="Vij">Ravi Vij</name><affiliation><nlm:aff id="A27">Barnes Jewish Hospital, Washington University School of Medicine, St. Louis, MO</nlm:aff></affiliation></author><author><name sortKey="Waller, Edmund K" sort="Waller, Edmund K" uniqKey="Waller E" first="Edmund K." last="Waller">Edmund K. Waller</name><affiliation><nlm:aff id="A28">Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA</nlm:aff></affiliation></author><author><name sortKey="Wiernik, Peter H" sort="Wiernik, Peter H" uniqKey="Wiernik P" first="Peter H." last="Wiernik">Peter H. Wiernik</name><affiliation><nlm:aff id="A29">Our Lady of Mercy Medical Center, Bronx, NY</nlm:aff></affiliation></author><author><name sortKey="Weisdorf, Daniel J" sort="Weisdorf, Daniel J" uniqKey="Weisdorf D" first="Daniel J." last="Weisdorf">Daniel J. Weisdorf</name><affiliation><nlm:aff id="A1">Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN</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="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Ph+ acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type, and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKI), mostly imatinib; 39% (RIC) and 49% (MAC) were MRD<sup>neg</sup> pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%;p=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (p=0.058). Overall survival was similar (RIC 39% [95% CI:27–52] vs. 35% [95% CI:270–44];p=0.62). Patients MRD<sup>pos</sup> pre-HCT had higher risk of relapse with RIC versus MAC (HR 1.97;p=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared to a similar MRD<sup>neg</sup> population after MAC (33%; p=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; p=0.057), but absence of pre-HCT TKI (HR 1.88;p=0.018), RIC (HR 1.891;p=0.054) and pre-HCT MRD<sup>pos</sup> (HR 1.6; p=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD<sup>neg</sup> status is preferred pre-HCT.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Moorman, Av" uniqKey="Moorman A">AV Moorman</name></author><author><name sortKey="Harrison, Cj" uniqKey="Harrison C">CJ Harrison</name></author><author><name sortKey="Buck, Ga" uniqKey="Buck G">GA Buck</name></author><author><name sortKey="Richards, Sm" uniqKey="Richards S">SM Richards</name></author><author><name sortKey="Secker Walker, Lm" uniqKey="Secker Walker L">LM Secker-Walker</name></author><author><name sortKey="Martineau, M" uniqKey="Martineau M">M Martineau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizuta, S" uniqKey="Mizuta S">S Mizuta</name></author><author><name sortKey="Matsuo, K" uniqKey="Matsuo K">K Matsuo</name></author><author><name sortKey="Yagasaki, F" uniqKey="Yagasaki F">F 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<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">23989431</article-id><article-id pub-id-type="pmc">3951192</article-id><article-id pub-id-type="doi">10.1038/leu.2013.253</article-id><article-id pub-id-type="manuscript">NIHMS549962</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: Impact of tyrosine kinase inhibitor and minimal residual disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bachanova</surname><given-names>Veronika</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Marks</surname><given-names>David I.</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Mei-Jie</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Hailin</given-names></name><degrees>MPH</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>de Lima</surname><given-names>Marcos</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Aljurf</surname><given-names>Mahmoud D.</given-names></name><degrees>MD, MPH</degrees><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Arellano</surname><given-names>Martha</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Artz</surname><given-names>Andrew S.</given-names></name><degrees>MD, MS</degrees><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Bacher</surname><given-names>Ulrike</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Cahn</surname><given-names>Jean-Yves</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Yi-Bin</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Copelan</surname><given-names>Edward A.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Drobyski</surname><given-names>William R.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Gale</surname><given-names>Robert Peter</given-names></name><degrees>MD, PhD, Dsc(hon), FACP</degrees><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Greer</surname><given-names>John P</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Gupta</surname><given-names>Vikas</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Hale</surname><given-names>Gregory A.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Kebriaei</surname><given-names>Partow</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Lazarus</surname><given-names>Hillard M.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lewis</surname><given-names>Ian D.</given-names></name><degrees>MBBS, PhD</degrees><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Lewis</surname><given-names>Victor A.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Liesveld</surname><given-names>Jane L.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Litzow</surname><given-names>Mark R.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Loren</surname><given-names>Alison W.</given-names></name><degrees>MD, MS</degrees><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Miller</surname><given-names>Alan M.</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Norkin</surname><given-names>Maxim</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Oran</surname><given-names>Betul</given-names></name><degrees>MD, MS</degrees><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Pidala</surname><given-names>Joseph</given-names></name><degrees>MD, MS</degrees><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Rowe</surname><given-names>Jacob M.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Savani</surname><given-names>Bipin N.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Saber</surname><given-names>Wael</given-names></name><degrees>MD, MS</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Vij</surname><given-names>Ravi</given-names></name><degrees>MBBS</degrees><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Waller</surname><given-names>Edmund K.</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Wiernik</surname><given-names>Peter H.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Weisdorf</surname><given-names>Daniel J.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN</aff><aff id="A2"><label>2</label>Bristol Adult BMT Unit, Bristol Children’s Hospital, Bristol, UNITED KINGDOM</aff><aff id="A3"><label>3</label>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI</aff><aff id="A4"><label>4</label>Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH</aff><aff id="A5"><label>5</label>King Faisal Specialist Hospital and Research Center, Riyadh, SAUDI ARABIA</aff><aff id="A6"><label>6</label>Winship Cancer Institute, Emory University, Atlanta, GA</aff><aff id="A7"><label>7</label>University of Chicago Medicine, Chicago, IL</aff><aff id="A8"><label>8</label>Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, GERMANY</aff><aff id="A9"><label>9</label>Department of Hematology, University Hospital, Grenoble, FRANCE</aff><aff id="A10"><label>10</label>Massachusetts General Hospital, Boston, MA</aff><aff id="A11"><label>11</label>Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC</aff><aff id="A12"><label>12</label>Medical College of Wisconsin, Milwaukee, WI</aff><aff id="A13"><label>13</label>Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UNITED KINGDOM</aff><aff id="A14"><label>14</label>Vanderbilt University Medical Center, Nashville, TN</aff><aff id="A15"><label>15</label>Princess Margaret Hospital, Toronto, ON, CANADA</aff><aff id="A16"><label>16</label>All Children’s Hospital, St. Petersburg, FL</aff><aff id="A17"><label>17</label>Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX</aff><aff id="A18"><label>18</label>Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, AUSTRALIA</aff><aff id="A19"><label>19</label>Alberta Children’s Hospital, Calgary, AB, CANADA</aff><aff id="A20"><label>20</label>Strong Memorial Hospital, University of Rochester Medical Center; Rochester, NY</aff><aff id="A21"><label>21</label>Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN</aff><aff id="A22"><label>22</label>Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA</aff><aff id="A23"><label>23</label>Baylor University Medical Center, Dallas, TX</aff><aff id="A24"><label>24</label>Shands HealthCare and University of Florida, Gainesville, FL</aff><aff id="A25"><label>25</label>Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL</aff><aff id="A26"><label>26</label>Department of Hematology, Rambam Medical Center, Haifa, ISRAEL</aff><aff id="A27"><label>27</label>Barnes Jewish Hospital, Washington University School of Medicine, St. Louis, MO</aff><aff id="A28"><label>28</label>Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA</aff><aff id="A29"><label>29</label>Our Lady of Mercy Medical Center, Bronx, NY</aff><author-notes><corresp id="cor1"><bold>Address for Correspondence:</bold> Veronika Bachanova, MD, PhD, Blood and Marrow Transplant Program, University of Minnesota, Mayo Mail Code 480; 420 Delaware Street SE, Minneapolis, MN 55455, <email>bach0173@umn.edu</email>, Phone: 612-624-5620; Fax: 612-625-6919</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>7</day><month>2</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>30</day><month>8</month><year>2013</year></pub-date><pub-date pub-type="ppub"><month>3</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>9</month><year>2014</year></pub-date><volume>28</volume><issue>3</issue><fpage>658</fpage><lpage>665</lpage><pmc-comment>elocation-id from pubmed: 10.1038/leu.2013.253</pmc-comment>
<permissions><license><license-p>Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: <uri xlink:type="simple" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</uri></license-p></license></permissions><abstract><p id="P1">The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Ph+ acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type, and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKI), mostly imatinib; 39% (RIC) and 49% (MAC) were MRD<sup>neg</sup> pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%;p=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (p=0.058). Overall survival was similar (RIC 39% [95% CI:27–52] vs. 35% [95% CI:270–44];p=0.62). Patients MRD<sup>pos</sup> pre-HCT had higher risk of relapse with RIC versus MAC (HR 1.97;p=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared to a similar MRD<sup>neg</sup> population after MAC (33%; p=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; p=0.057), but absence of pre-HCT TKI (HR 1.88;p=0.018), RIC (HR 1.891;p=0.054) and pre-HCT MRD<sup>pos</sup> (HR 1.6; p=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD<sup>neg</sup> status is preferred pre-HCT.</p></abstract><kwd-group><kwd>Acute lymphoblastic leukemia</kwd><kwd>Philadelphia chromosome</kwd><kwd>reduced intensity conditioning</kwd><kwd>allograft</kwd><kwd>minimal residual disease</kwd><kwd>tyrosine-kinase inhibitor</kwd></kwd-group></article-meta></front><body><sec sec-type="intro" id="S1"><title>INTRODUCTION</title><p id="P2">Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is the largest genetically defined subset, affecting about 25% of adults with ALL; particularly those older than 40 years.<sup><xref rid="R1" ref-type="bibr">1</xref></sup> The poor survival of Ph+ ALL patients treated with chemotherapy alone (10%) has been substantially improved through the use of allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR1) and more recently, by combining tyrosine kinase inhibitors (TKI) with induction and post-remission chemotherapy.<sup><xref rid="R2" ref-type="bibr">2</xref>–<xref rid="R5" ref-type="bibr">5</xref></sup> The anti-leukemia effect of HCT is through chemotherapy and/or radiation used in the preparative regimen and through an immune-mediated graft-versus-leukemia (GVL) effect.<sup><xref rid="R5" ref-type="bibr">5</xref>–<xref rid="R8" ref-type="bibr">8</xref></sup> Although widespread use of TKIs has changed the landscape of Ph+ ALL management, myeloablative conditioning (MAC) followed by the allogeneic HCT remains the only established curative therapy. Incorporating TKIs into induction chemotherapy has not increased toxicity, but has substantially improved remission rates and facilitated more allotransplants in CR1.<sup><xref rid="R9" ref-type="bibr">9</xref>, <xref rid="R10" ref-type="bibr">10</xref></sup> Furthermore, several prospective clinical trials testing an imatinib-containing strategy consolidated with a MAC alloHCT showed overall survival (OS) ranging from 40–65%, which is markedly better than historical pre-imatinib controls (OS 20–40%).<sup><xref rid="R2" ref-type="bibr">2</xref>–<xref rid="R4" ref-type="bibr">4</xref>, <xref rid="R11" ref-type="bibr">11</xref>–<xref rid="R13" ref-type="bibr">13</xref></sup> However, many patients are not eligible for a conventional myeloablative conditioning regimen due to their age and comorbidities. High transplant-related mortality (TRM) remains a serious problem in older adults which negates the survival benefit gained through protection from relapse by full intensity conditioning and GVL.<sup><xref rid="R14" ref-type="bibr">14</xref></sup> For these reasons, RIC HCT was developed to allow engraftment and harness the GVL effect while potentially limiting TRM in patients unfit for full intensity conditioning regimens</p><p id="P3">To date, there are no large-scale data on the efficacy of RIC HCT for Ph+ ALL. Most single institution studies lack detail on ALL subset-specific outcomes.<sup><xref rid="R15" ref-type="bibr">15</xref>–<xref rid="R19" ref-type="bibr">19</xref></sup> The utility of RIC HCT for ALL was recently demonstrated in a CIBMTR study for Ph negative ALL, in which similar rates of TRM, relapse, and survival (43% vs 38%) between RIC and MAC were observed.<sup><xref rid="R20" ref-type="bibr">20</xref></sup> A European Bone Marrow Transplant (EBMT) Registry study, which included 41 Ph+ patients in a RIC cohort, showed comparable OS between RIC and MAC groups.<sup><xref rid="R21" ref-type="bibr">21</xref></sup> However, the limited details on minimal residual disease (MRD) and TKI use make the interpretation of these studies problematic. Indeed, the definition of remission in Ph+ ALL now routinely includes tools to assess the depth of remission by cytogenetic testing of interphase cells for t(9;22) (fluorescent in situ hybridization [FISH]) and PCR for detection of chimeric mRNA arising from BCR-ABL1 genomic recombination. FISH assay allows the sensitivity between 0.5–3%, while real-time PCR and nested PCR allow quantification of MRD to the 1:10<sup>5</sup>-10<sup>6</sup> cell level.<sup><xref rid="R22" ref-type="bibr">22</xref></sup> Both assays are widely used to monitor response and guide therapeutic choices.<sup><xref rid="R17" ref-type="bibr">17</xref>,<xref rid="R23" ref-type="bibr">23</xref>–<xref rid="R26" ref-type="bibr">26</xref></sup> Several studies in adult Ph+ ALL have confirmed that patients with MRD persistence 6–10 weeks after initiating induction therapy have a higher risk of relapse, yet early myeloablative allogeneic donor HCT can sometimes overcome MRD<sup>pos</sup> and cure a subset of patients.<sup><xref rid="R25" ref-type="bibr">25</xref>, <xref rid="R27" ref-type="bibr">27</xref></sup> The sensitivity of Ph+ ALL to non-ablative chemotherapy/radiation and to GVL in the setting of RIC HCT is not well established. To address these issues, we performed a multicenter registry-based analysis investigating the outcomes of RIC allogeneic HCT for Ph+ ALL. Using a matched pair design, we examined a cohort of patients with Ph+ALL in CR1 and compared survival after RIC or MAC allogeneic transplantation, as well as the effect of TKI use and pre-HCT MRD status on transplant outcomes.</p></sec><sec sec-type="subjects|methods" id="S2"><title>PATIENTS AND METHODS</title><sec id="S3"><title>Data source</title><p id="P4">The CIBMTR (Center for International Bone Marrow Transplant Research), a voluntary working group of more than 450 transplantation centers worldwide, collects data on consecutive allogeneic HCTs at a statistical center housed at both the Medical College of Wisconsin (Milwaukee, WI) and the National Marrow Donor Program (Minneapolis, MN). Patients are observed longitudinally with yearly follow-up. Computerized checks for errors and onsite audits of participating centers ensure data quality. The present study was conducted with a waiver of informed consent and in compliance with Health Insurance Portability and Accountability Act regulations as determined by the Institutional Board and the Privacy Officer of the Medical College of Wisconsin.</p></sec><sec id="S4"><title>Patient Selection</title><p id="P5">We included patients aged 18 and older with Ph+ALL in CR1 who had received HLA allele matched related or matched or mismatched unrelated donor (URD) HCT between 2000 and 2009. Well matched URD were either 8/8 or 6/6 matched at Class 1 as recommended by CIBMTR.<sup><xref rid="R26" ref-type="bibr">26</xref></sup> Umbilical cord blood donors, mismatched related donor and ex vivo T cell-depleted grafts were excluded. Preparative regimens were classified either as RIC or MAC according to published consensus definitions.<sup><xref rid="R28" ref-type="bibr">28</xref></sup> The CIBMTR definition of RIC included regimens containing melphalan ≤ 150mg/m2 (n=24), busulfan ≤ 9mg/kg orally (n=20), total body irradiation <5 Gy (TBI; n=11), fludarabine-TBI combinations (n=17), or fludarabine-based conditioning (n=5). The MAC preparative regimen consisted mostly of TBI (n=108) or busulfan combinations (n=22). RIC patients were matched with MAC patients on 3 factors: age (within 15 years), type of donor (related versus URD), and year of transplant (within 5 years). A <xref ref-type="supplementary-material" rid="SD1">supplemental data</xref> form was developed to collect: 1) presence of pre-HCT MRD in bone marrow immediately prior to conditioning tested by FISH and/or by PCR for the BCR-ABL (yes/no); and 2) use of TKIs (imatinib, nilotinib or dasatinib) delivered at any time prior to transplantation and the duration of TKI therapy. We also collected data on post-transplant TKI administration, defined as maintenance therapy (excluding treatment given for cytogenetic or morphologic relapse), start date and duration of maintenance. Retrospectively collecting the MRD data from many centers reflects the real world clinical practice where both BCR/ABL transcript levels and/or FISH analysis are often obtained in patients with morphologic CR. The stringency of MRD determination using each center’s testing sensitivity with these approaches could not be addressed in this multicenter analysis. Data on post-transplant MRD monitoring were not collected. The final study population excluded MAC patients not selected by the matching strategy (n=241) and those without <xref ref-type="supplementary-material" rid="SD1">supplemental data</xref> (n=32). The return rate on supplemental forms requested on 243 cases from 76 centers was 86.4%. Each participating center enrolled an average 2.5 cases (range 1–15 cases).</p></sec><sec id="S5"><title>Definitions, Study Endpoints and Statistical Analysis</title><p id="P6">The primary outcomes were OS after HCT defined as the time from transplantation to death, disease-free survival (DFS), relapse incidence and TRM. Surviving patients were censored at the time of last contact. Secondary endpoints were grade II-IV acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). Probability of DFS and OS were calculated using the Kaplan-Meier estimator, with the variance estimated by Greenwood’s formula. Values for other endpoints were calculated using cumulative incidence curves to accommodate competing risks.<sup><xref rid="R29" ref-type="bibr">29</xref></sup> We defined the MRD status as MRD<sup>pos</sup> (Ph+ by FISH positive and/or positive BCR-ABL by PCR) and pre-HCT MRD<sup>neg</sup> (Ph+ FISH negative and/or negative BCR-ABL by PCR). Use of TKI was defined as pre-HCT TKI (including 41 patients who received TKI both pre and post-HCT) or no TKI at any time-point. The risk factors considered in the stepwise model building procedures were conditioning regimen intensity (main effect), age, gender, pre-HCT MRD positivity, TKI use pre-HCT (yes/no), year of HCT and cGVHD as a time-dependent covariate. The potential interactions between the main effect (conditioning regimen) and MRD, TKI and other significant variables were examined.</p></sec></sec><sec sec-type="results" id="S6"><title>RESULTS</title><sec id="S7"><title>Patients Characteristics</title><p id="P7">Data on 197 eligible patients from 14 different countries and 76 reporting centers were analyzed. Sixty-seven RIC patients were matched for analysis 1:2 (n=63) or 1:1 (n=4) to 130 MAC patients for age, donor type, and year of transplant (<xref ref-type="table" rid="T1">Table 1</xref>). Median age in the RIC and MAC groups was 54 and 50 years, respectively (p=0.02). WBC count at diagnosis and performance status at time of transplant were similar for both groups. Previous fungal infections were more common in the RIC group (12% vs 3%; p=0.006). RIC recipients had a longer median time from diagnosis to HCT (6 months (interquartile range 4.8–7.4 months) vs MAC: 5 months (interquartile range 4.2–6.8 months; p=0.03), but the time from diagnosis to CR1 was similar (median 42 days (interquartile range 34–82 days) and 52 days (interquartile range 31–111 days; p=0.76) in RIC and MAC groups. Over half of patients in both groups had co-existent morbidities or organ impairment (61% in RIC and 58% in MAC; p=0.12). Significantly more RIC patients had a pre-HCT comorbidity index of ≥1 as compared to MAC patients (19% vs 8%; p=0.03).<sup><xref rid="R30" ref-type="bibr">30</xref></sup> Both RIC and MAC groups used peripheral blood grafts more often than bone marrow grafts and had similar use of related donors (39% and 38%) and matched URD (42% for both). GVHD prophylaxis was similar in both groups with cyclosporine or tacrolimus-containing-regimens used most often. RIC patients more often received anti-thymocyte globulin or campath (37% vs 17%; p=0.03). The remaining variables of donor/recipient sex, donor/recipient CMV status and year of transplant were balanced. Median follow-up of survivors was 49 months (range 3–108 months) for the RIC group and 61 months (range 3–119 months) for the MAC group.</p></sec><sec id="S8"><title>MRD assessment and use of TKI inhibitors</title><p id="P8">All patients were in CR1 by morphologic criteria. Reflecting the clinical practice, more patients had pre-HCT bone marrow MRD evaluation by FISH (RIC: 89%; MAC: 88%) than PCR (RIC: 64%; MAC: 63%). 185 subjects (94% of all patients; RIC: 97%; MAC: 92%) were investigated by at least one MRD method prior to transplant at median time 25 days (interquartile range: 14–122 days; only 46% reported the MRD test date). Similar proportions of RIC and MAC recipients were FISH<sup>pos</sup> (34% vs 38%), PCR BCR/ABL<sup>pos</sup> (50% vs 35%) and positive by either or both methods (MRD<sup>pos</sup> 58% and 47%; p=0.79; <xref ref-type="table" rid="T1">Table 1</xref>).</p><p id="P9">Before 2005, 60% received TKI pre-transplant compared to nearly 90% after 2005 (p<0.01). All but 2 patients received imatinib pre-HCT (the pre-HCT TKI group); including who 2 received dasatinib pre-HCT. The median duration of TKI pre-HCT was 7 months (RIC) and 6 months (MAC). Among 153 patients given TKI pre-HCT, 41% became MRD<sup>neg</sup> pre-HCT. Among 44 patients not receiving TKI, 48% were MRD<sup>neg</sup>. The rate of MRD negativity was not better in those receiving prolonged pre-HCT TKI (>6 months 38% vs <6 months 42%; p=0.44).</p><p id="P10">Only 43 (<25%) patients (RIC n=21; MAC n=22) received TKI post-transplant for maintenance. Data on the drug, dose, and treatment duration were not available. The majority of patients (90% in RIC and 77% in MAC) who received TKI post-transplant were MRD<sup>pos</sup> pre-HCT. The median time to TKI administration after RIC HCT was 1.5 months (interquartile range: 0.9 −3.5 months), about 1 month earlier than MAC HCT (2.9 months [interquartile range 1.7–5.5 months]; p=0.095). Forty-one patients (20%) were not treated with TKI agents at any time.</p></sec><sec id="S9"><title>DFS and OS</title><p id="P11">At 3 years, DFS and OS for the RIC group were 26% (95% CI 16–37%) and 39% (95% CI 27–52%), respectively and were similar to the MAC group (28% [95%CI 20–36%] and 35% [95%CI 27–44%]; <xref ref-type="table" rid="T2">Table 2</xref>). In univariate analysis, pre-HCT MRD status did not impact survival in either group (<xref ref-type="fig" rid="F1">Figure 1B</xref>). Sex, peripheral WBC at diagnosis and year of HCT did not significantly affect OS in univariate analysis (male gender HR: 1.17 (95%CI 0.8–1.6); WBC>100×10<sup>9</sup>/L: HR 0.6 [95%CI 0.32–1.1], 2005–2009 HR: 1.05 [95%CI 0.7–1.5]. Within the RIC group, both pre-HCT TKI and concomitant MRD<sup>neg</sup> status yielded the best 3-year OS (55% [95%CI 31–77%]), which compared favorably to the same patients (MRD<sup>neg</sup> with pre-HCT TKI) in the MAC group (33% ([95% CI 20–48%]); p= 0.0042).</p><p id="P12">In multivariate analysis, RIC did not significantly influence OS (HR 0.87; p=0.48) or DFS (HR 1.1; p=0.58; <xref ref-type="table" rid="T3">Table 3</xref>). Age above 40 years was associated with significantly worse survival (HR 1.92), but pre-HCT MRD status, pre-HCT TKI use and the development of cGVHD did not significantly alter OS or DFS (<xref ref-type="table" rid="T3">Table 3</xref>).</p></sec><sec id="S10"><title>TRM and Causes of Death</title><p id="P13">The cumulative incidence of TRM at day 100 was 10% in the RIC group (95% CI 4–19%) and 19% in the MAC group (95%CI 13–26%; p=0.11), while at 1 year it was almost 3-fold lower in the RIC than in the MAC group (13% vs 36%; p<0.001; <xref ref-type="fig" rid="F1">Figure 1C</xref>). In adjusted multivariate analysis, RIC was associated with reduced TRM risk (HR 0.60; p=0.059). Age over 40 years increased the risk of TRM 3-fold and cGVHD increased TRM risk 1.7-fold (<xref ref-type="table" rid="T3">Table 3</xref>). The most common cause of death in the RIC group was relapse (n=13) followed by infection (n=10), organ failure (n=6), and GVHD (n=4). MAC patients died most often of GVHD (n=22), relapse (n=16), and infection (n=12). Death attributed to GVHD was more common after MAC compared to RIC HCT (p=0.1).</p></sec><sec id="S11"><title>Relapse</title><p id="P14">The incidence of relapse at 3 years was higher in the RIC group (49%) than in the MAC group (28%) although not statistically significant (p=0.058; <xref ref-type="table" rid="T2">Table 2</xref>). Given that pre-HCT MRD and use of TKI could potentially modify relapse risk, we examined relapse risks in specified subgroups. The cumulative incidence of relapse at 3 years in pre-HCT MRD<sup>pos</sup> patients was significantly higher after RIC 61% (95%CI 45–76%]) than MAC HCT (35% [95% CI 24–48%]; HR 1.97 [1.09–3.57; p=0.026]; <xref ref-type="fig" rid="F1">Figure 1A</xref>). However, pre-HCT MRD<sup>neg</sup> patients had similar relapse risks after RIC or MAC transplants (31% [95% 15–50%]) vs 21% [11–32%]); p=0.15). Low relapse rate was also observed in subset of patients who were pre-HCT BCR/ABL<sup>neg</sup> (RIC 16% [95%CI 7–28]; MAC 25% [9–46%]; p=0.36).</p><p id="P15">In the RIC group, pre-HCT TKI therapy was associated with 2-fold reduction in 3- year relapse incidence (38%[95% CI 25–52%]) as compared to no pre-HCT TKI (81% [95%CI 59–96%]; p=0.0039). In contrast, in the MAC group no protection from relapse by pre-HCT TKI was observed (26% [95%CI, 18%–35%] vs 33% [95%CI 17–52%]; p=0.51). Remarkably low rates of relapse were observed in patients who received pre-HCT TKI who were also pre-HCT MRD<sup>neg</sup> (RIC 17% [95%CI 4–37%] and MAC HCT 20% [95%CI, 10–33%]). For these patients, the conditioning regimen intensity did not influence relapse risk. The 3-yr relapse was not impacted by TKI post-transplant maintenance neither in the RIC cohort (TKI maintenance 59% vs. no TKI 45%; p=0.63) nor in the MAC cohort (TKI maintenance 27% vs no TKI 28%; p=0.26), although only 43 patients were treated with TKI post-transplant. The median time from HCT to relapse was similar at 11 months in the RIC group (range 1–103 months) and 9 months in the MAC group (range 1–119 months; p= 0.60).</p><p id="P16">In adjusted multivariate analysis, RIC was associated with increased risk of relapse (HR 1.84; p=0.011). While age (>40 years) and cGVHD did not influence relapse risk, no TKI use pre-HCT (HR 1.88; p=0.018) was independently associated with an increased risk of relapse. Pre-HCT MRD<sup>pos</sup> (HR 1.6, [95%CI 0.96–2.67]) was associated with increased relapse risk, but did not reach statistical significance (<xref ref-type="table" rid="T3">Table 3</xref>).</p></sec><sec id="S12"><title>Donor lymphocyte infusions and second transplant</title><p id="P17">Fourteen patients received donor lymphocyte infusion (DLI) post-transplant (RIC 3; MAC 11). Six DLI infusions were administered for relapsed ALL and all were in the MAC cohort. None of the 6 patients survive. Three of 8 patients who received DLI for non-relapse indications are alive (two in RIC and one in MAC cohort). Seventeen other patients underwent second HCT for relapsed ALL (RIC cohort 6; MAC cohort 11) and three (17%) survive (2 in RIC and 1 in the initial MAC cohort) after their 2<sup>nd</sup> HCT.</p></sec><sec id="S13"><title>GVHD</title><p id="P18">The cumulative incidence of Grade II-IV aGVHD at day 100 was lower in the RIC (30% [95%CI 20–42%]) than the MAC group (47% [95%CI 39–56%]; p=0.014). The incidence of cGVHD at 1 year was similar (RIC 46% [95% 34–58%] vs. MAC 41% [95%CI 32–50%]; p=0.38). Given the recent use of TKIs for treatment of cGVHD, we analyzed the relationship between GVHD and TKI administration after HCT. The median time from HCT to aGVHD diagnosis was 0.9 month (range 0.2–2.7 months), while the median time to start TKI therapy post-transplant was later: 2.3 months (range 0.5–36 months). More importantly, the time from HCT to cGVHD onset was similar in the subgroup treated with TKI (4.4 months) versus no TKI therapy (5.8 months). Additionally, TKI administration post HCT did not reduce the incidence of cGVHD as the proportion of patients with cGVHD was similar with or without post-HCT TKI (63% vs 45%; p= 0.87). In multivariate analysis, pre-HCT MRD and TKI use did not impact risks of acute or chronic GVHD. After adjusting for age, MRD and TKI use, the risk of aGVHD was significantly lower in the RIC group (HR 0.54; p=0.014; <xref ref-type="table" rid="T3">Table 3</xref>), while the risk of cGVHD was not altered by conditioning regimen intensity.</p></sec></sec><sec sec-type="discussion" id="S14"><title>Discussion</title><p id="P19">To examine the role of conditioning regimen intensity, MRD and TKI influences on HCT for ALL, we conducted a multicenter retrospective matched-pair analysis of 197 Ph+ ALL patients undergoing RIC and MAC allogeneic HCT in CR1. The strength and clinical applicability of this study is enhanced by the incorporation of data on pre-HCT MRD status and administration of TKI pre-HCT-- two critical outcome-modifying variables. In addition, given the matched pair study design, the median age of 52 years closely reflects the HCT population with Ph+ ALL.</p><p id="P20">The main finding is that DFS and OS in Ph+ ALL were similar after RIC and MAC allogeneic HCT, confirming the curative potential of allogeneic HCT after a reduced intensity preparative regimen. The relatively mature follow-up of 4 years suggests that long-term survival can be achieved for about 40% of older patients with Ph+ ALL after RIC HCT. Hence, RIC extends the benefit of allotransplant to patients above age 50 and to those who are otherwise ineligible for conventional MAC HCT. While there is still considerable room for improvement, these results are encouraging given the disappointing long-term outcomes observed without HCT. In some studies, patients ineligible for HCT have been treated with TKI-based maintenance therapy.<sup><xref rid="R3" ref-type="bibr">3</xref>, <xref rid="R4" ref-type="bibr">4</xref>, <xref rid="R31" ref-type="bibr">31</xref>, <xref rid="R32" ref-type="bibr">32</xref></sup> Although early results with short follow-up were promising, late relapses still occurred after a median duration of remission of 20–25 months and this approach currently cannot be considered curative. Most relapses were associated with a highly resistant phenotype and BCR-ABL gene mutations including T315I.<sup><xref rid="R33" ref-type="bibr">33</xref>, <xref rid="R34" ref-type="bibr">34</xref></sup> As a result, the value of RIC HCT compared to chemotherapy plus TKI for older patients with Ph+ ALL remains a key issue for future prospective trials.</p><p id="P21">RIC HCT conferred the most significant benefit to the patients who were MRD<sup>neg</sup> prior to allograft and had received TKI pre-HCT. Indeed, the 2-fold increase in relapse in patients with pre-HCT MRD<sup>pos</sup> evident only in the RIC group suggests that a less intense regimen may not overcome the presence of residual detectable leukemia and that caution is needed when RIC is considered for MRD<sup>pos</sup> patients. Notably, higher use of ATG in RIC group may contribute to higher relapse risk.<sup><xref rid="R35" ref-type="bibr">35</xref></sup> Nevertheless, the favorable outcomes in MRD<sup>neg</sup> patients suggest that achieving a MRD negative state prior to HCT is vitally important and highlight the need to use effective therapy or perhaps second/third generation TKI pre-HCT for those MRD<sup>pos</sup> patients in whom RIC is planned.<sup><xref rid="R38" ref-type="bibr">38</xref></sup> In our study, both pre-HCT TKI and MRD<sup>neg</sup> status in RIC patients best protected patients from relapse (only 17% relapsed) and were associated with superior OS of 55%. Use of TKI pre-HCT could lead to deeper MRD negativity; however off-target immunomodulatory antileukemia effects of TKI have been also reported. Interestingly, recent clinical studies suggested development of BCR-ABL-specific cytotoxic T cells in the bone marrow of patients with Ph+ ALL during long-term imatinib treatment.<sup><xref rid="R36" ref-type="bibr">36</xref></sup> In addition to TKI, other targeted therapeutic interventions such as blinatumomab and cellular infusions could also be of benefit if used prior to RIC HCT or peritransplant.<sup><xref rid="R36" ref-type="bibr">36</xref>–<xref rid="R40" ref-type="bibr">40</xref></sup></p><p id="P22">Importantly, we showed that reducing the intensity of the preparative regimen can substantially lower risks of acute GVHD and TRM. This finding is particularly important because higher risks of TRM limit the utility of HCT, particularly for older individuals in whom Ph+ ALL is often diagnosed.<sup><xref rid="R14" ref-type="bibr">14</xref></sup> The observed low TRM (13% at 1 year) is striking, even acknowledging the inherent selection bias associated with RIC patients, who are usually at a greater risk of transplant-related toxicity.</p><p id="P23">Because of the retrospective registry study design, we were not able to quantify the depth of MRD and its influence on survival. Both assays have limitations and while PCR is highly sensitive, false negative results can be seen due to exquisite susceptibility of RNA to degradation.<sup><xref rid="R22" ref-type="bibr">22</xref></sup> Variations in transcript levels detectable by PCR complemented by assessment using FISH temper the implications of these data and highlight the need for prospective validation using standardized BCR/ABL testing. Nevertheless, Ph+ ALL remains an important ALL subset for which RIC HCT is being tested and until prospective trial results become available, our analysis provides real life, clinically relevant insights on allograft approaches for patients with Ph+ALL in morphologic remission. Current evidence suggests that MRD<sup>pos</sup> status after induction/consolidation chemotherapy predicts for an increased risk of relapse and worse survival. In a prospective study by Bassan et al. on 236 patients; 48% remained MRD<sup>pos</sup> after induction/consolidation and 36 patients (66%) underwent HCT rescuing a proportion of MRD<sup>pos</sup> by MAC HCT.<sup><xref rid="R41" ref-type="bibr">41</xref></sup> Our data also suggest that MAC allotransplantation can reduce the adverse relapse risk conferred by a pre-HCT MRD<sup>pos</sup> status. Other studies reported evidence that MRD<sup>pos</sup> patients treated with allogeneic HCT can have successful outcomes,<sup><xref rid="R24" ref-type="bibr">24</xref>–,<xref rid="R26" ref-type="bibr">26</xref></sup> although post-transplant persistence of MRD<sup>pos</sup> most often predicts imminent relapse and poor DFS. A recent GRALL report showed improved OS after imatinib-based chemotherapy followed by MAC HCT (50%) compared to no allo-HCT (33%). Although MRD<sup>pos</sup> predicted higher risk of relapse, it did not influence OS.<sup><xref rid="R4" ref-type="bibr">4</xref></sup></p><p id="P24">The emerging future question of great importance is the value serial monitoring of BCR/ABL post-transplant and screening for BCR/ABL mutations. Impact of post-HCT TKI on relapse in this study has to be interpreted with caution because 70–80% of patients did not receive TKI post-HCT in maintenance. This might reflect the earlier era of study or poor tolerance of TKI post-transplant related to myelosuppression or other adverse effects as reported.<sup><xref rid="R11" ref-type="bibr">11</xref>,<xref rid="R42" ref-type="bibr">42</xref></sup> A recent German prospective trial randomized Ph+ ALL patients after MAC HCT to receive either maintenance imatinib or pre-emptive therapy with imatinib for molecular relapse. They concluded that post-transplant imatinib was often delayed or interrupted, but no difference in survival was observed with either approach. The study reported excellent OS of 70% in both groups; however, only those patients who were alive at day 60 were included in the analysis.<sup><xref rid="R42" ref-type="bibr">42</xref></sup></p><p id="P25">Other strategies of post-HCT manipulations such as DLI and second transplant are often available. Though rarely used in our cohort, these efforts did not significantly alter the outcome.</p><p id="P26">Our results provide directly applicable clinical data for clinicians and supports prospective application of RIC for Ph+ ALL patients who are ineligible for MAC such as the current prospective UKALL 14 clinical trial which offers RIC HCT to Ph+ ALL patients older than 40. Our results suggest that achieving MRD<sup>neg</sup> status may lead to low relapse and prolonged survival from either MAC or RIC HCT and that MRD status and fitness rather than a pre-defined age cut-off may better guide decisions about conditioning intensity prior to allogeneic HCT. The use of TKI post- transplant requires further study before it can be considered standard of care.</p></sec><sec sec-type="supplementary-material" id="SM"><title>Supplementary Material</title><supplementary-material content-type="local-data" id="SD1"><label>1</label><media xlink:href="NIHMS549962-supplement-1.pdf" orientation="portrait" xlink:type="simple" id="d37e990" position="anchor"></media></supplementary-material></sec></body><back><ack id="S15"><title>ACKNOWLEDGMENT</title><p id="P27">This work was supported in part by Novartis providing the grant to CIBMTR for <xref ref-type="supplementary-material" rid="SD1">supplemental data</xref> collection. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24 CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement U10 HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Allos Therapeutics, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;Gentium SpA; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government.</p></ack><fn-group><fn id="FN1" fn-type="conflict"><p id="P28"><bold>AUTHORSHIP AND CONFLICT OF INTEREST STATEMENT</bold></p><p id="P29">No conflict of interest: Authors declare no competing financial interests.</p><p id="P30">V. 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person-group-type="author"><name><surname>Pfeifer</surname><given-names>H</given-names></name><name><surname>Wassmann</surname><given-names>B</given-names></name><name><surname>Bethge</surname><given-names>W</given-names></name><name><surname>Dengler</surname><given-names>J</given-names></name><name><surname>Bornhauser</surname><given-names>M</given-names></name><name><surname>Stadler</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR-ABL1 positive acute lymphoblastic leukemia</article-title><source>Leukemia</source><year>2012</year><volume>27</volume><issue>6</issue><fpage>1254</fpage><lpage>62</lpage><pub-id pub-id-type="pmid">23212150</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><p id="P34"><bold>(A)</bold> Kaplan-Meier estimate of overall survival using reduced intensity or myeloablative conditioning HCT for Ph+ ALL by MRD status</p><p id="P35"><bold>(B)</bold> Cumulative incidence of relapse by pre HCT MRD and conditioning intensity</p><p id="P36"><bold>(C)</bold> Cumulative incidence of treatment related mortality</p></caption><graphic xlink:href="nihms549962f1a"></graphic><graphic xlink:href="nihms549962f1b"></graphic><graphic xlink:href="nihms549962f1c"></graphic></fig><table-wrap id="T1" position="float" orientation="portrait"><label>Table 1</label><caption><p id="P37">Characteristics of adults with Ph+ ALL who received reduced intensity conditioning (RIC) allogeneic donor HCT in CR1 between 2000–2009 and a matched cohort receiving myeloablative (MAC) allogeneic HCT</p></caption><table frame="below" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Variable</th><th align="right" rowspan="1" colspan="1">RIC</th><th align="right" rowspan="1" colspan="1">MAC</th><th align="center" rowspan="1" colspan="1">P-value</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Number of patients</td><td align="right" rowspan="1" colspan="1">67</td><td align="right" rowspan="1" colspan="1">130</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Number of centers</td><td align="right" rowspan="1" colspan="1">30</td><td align="right" rowspan="1" colspan="1">66</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Age, median (range)</td><td align="right" rowspan="1" colspan="1">54 (19–69)</td><td align="right" rowspan="1" colspan="1">50 (19–66)</td><td align="center" rowspan="1" colspan="1">0.02</td></tr><tr><td align="left" rowspan="1" colspan="1">Sex</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.94</td></tr><tr><td align="left" rowspan="1" colspan="1"> Male</td><td align="right" rowspan="1" colspan="1">37 (55)</td><td align="right" rowspan="1" colspan="1">71 (55)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Female</td><td align="right" rowspan="1" colspan="1">30 (45)</td><td align="right" rowspan="1" colspan="1">59 (45)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Karnofsky score</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.36</td></tr><tr><td align="left" rowspan="1" colspan="1"> < 80%</td><td align="right" rowspan="1" colspan="1">8 (12)</td><td align="right" rowspan="1" colspan="1">8 (6)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> 80 – 100%</td><td align="right" rowspan="1" colspan="1">54 (81)</td><td align="right" rowspan="1" colspan="1">113 (87)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">5 (7)</td><td align="right" rowspan="1" colspan="1">9 (7)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">HCT Comorbidity Index</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.03</td></tr><tr><td align="left" rowspan="1" colspan="1"> 0</td><td align="right" rowspan="1" colspan="1">54 (81)</td><td align="right" rowspan="1" colspan="1">119 (92)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ≥1</td><td align="right" rowspan="1" colspan="1">13 (19)</td><td align="right" rowspan="1" colspan="1">11 (8)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Fungal infection prior to HCT</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.006</td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="right" rowspan="1" colspan="1">57 (85)</td><td align="right" rowspan="1" colspan="1">126 (97)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="right" rowspan="1" colspan="1">8 (12)</td><td align="right" rowspan="1" colspan="1">4 (3)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">2 (3)</td><td align="right" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">WBC at diagnosis, ×10^9/L</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.23</td></tr><tr><td align="left" rowspan="1" colspan="1"> < 30</td><td align="right" rowspan="1" colspan="1">41 (61)</td><td align="right" rowspan="1" colspan="1">70 (54)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> 30 – 100</td><td align="right" rowspan="1" colspan="1">14 (21)</td><td align="right" rowspan="1" colspan="1">23 (18)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> > 100</td><td align="right" rowspan="1" colspan="1">5 (7)</td><td align="right" rowspan="1" colspan="1">24 (18)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">7 (10)</td><td align="right" rowspan="1" colspan="1">13 (10)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Cytogenetic abnormalities</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.34</td></tr><tr><td align="left" rowspan="1" colspan="1"> t(9:22) only</td><td align="right" rowspan="1" colspan="1">32 (48)</td><td align="right" rowspan="1" colspan="1">48 (37)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> t(9:22) and other</td><td align="right" rowspan="1" colspan="1">25 (37)</td><td align="right" rowspan="1" colspan="1">58 (45)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Other</td><td align="right" rowspan="1" colspan="1">4 (6)</td><td align="right" rowspan="1" colspan="1">5 (4)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">6 (9)</td><td align="right" rowspan="1" colspan="1">19 (15)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Time from diagnosis to 1<sup>st</sup> complete remission</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.76</td></tr><tr><td align="left" rowspan="1" colspan="1"> Median (interquartile range) in days</td><td align="right" rowspan="1" colspan="1">42 (34–82)</td><td align="right" rowspan="1" colspan="1">52 (31–111)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">1 (1)</td><td align="right" rowspan="1" colspan="1">7 (5)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Time from diagnosis to transplant</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.02</td></tr><tr><td align="left" rowspan="1" colspan="1"> ≤ 5 months</td><td align="right" rowspan="1" colspan="1">20 (30)</td><td align="right" rowspan="1" colspan="1">64 (49)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> > 5 months</td><td align="right" rowspan="1" colspan="1">46 (69)</td><td align="right" rowspan="1" colspan="1">66 (51)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">1 (1)</td><td align="right" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Minimal residual disease pre-HCT</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> FISH tested</td><td align="right" rowspan="1" colspan="1">59 (88)</td><td align="right" rowspan="1" colspan="1">113 (87)</td><td align="center" rowspan="1" colspan="1">0.75</td></tr><tr><td align="left" rowspan="1" colspan="1"> FISH neg/tested for MRD</td><td align="right" rowspan="1" colspan="1">36/59 (54)</td><td align="right" rowspan="1" colspan="1">63/113 (48)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> FISH pos/tested for MRD</td><td align="right" rowspan="1" colspan="1">23/59 (34)</td><td align="right" rowspan="1" colspan="1">50/113 (38)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> FISH not performed or unknown</td><td align="right" rowspan="1" colspan="1">8 (12)</td><td align="right" rowspan="1" colspan="1">17 (13)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> BCR/ABL PCR tested</td><td align="right" rowspan="1" colspan="1">42 (63)</td><td align="right" rowspan="1" colspan="1">82 (63)</td><td align="center" rowspan="1" colspan="1">0.73</td></tr><tr><td align="left" rowspan="1" colspan="1"> PCR neg/tested for MRD</td><td align="right" rowspan="1" colspan="1">21/42 (50)</td><td align="right" rowspan="1" colspan="1">46/82 (35)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> PCR pos/tested for MRD</td><td align="right" rowspan="1" colspan="1">21/42 (50)</td><td align="right" rowspan="1" colspan="1">36/82 (28)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> PCR not performed or unknown</td><td align="right" rowspan="1" colspan="1">24 (36)</td><td align="right" rowspan="1" colspan="1">48 (37)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>neg</sup><xref ref-type="table-fn" rid="TFN2">**</xref></td><td align="right" rowspan="1" colspan="1">26 (39)</td><td align="right" rowspan="1" colspan="1">58 (49)</td><td align="center" rowspan="1" colspan="1">0.79</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>pos</sup><xref ref-type="table-fn" rid="TFN1">*</xref></td><td align="right" rowspan="1" colspan="1">39 (58)</td><td align="right" rowspan="1" colspan="1">62 (47)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">TKI use prior to HCT</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.71</td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="right" rowspan="1" colspan="1">16 (24)</td><td align="right" rowspan="1" colspan="1">28 (22)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="right" rowspan="1" colspan="1">51 (76)</td><td align="right" rowspan="1" colspan="1">102 (78)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Duration of TKI pre HCT, months</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.41</td></tr><tr><td align="left" rowspan="1" colspan="1"> Median (range)</td><td align="right" rowspan="1" colspan="1">7 (1–12)</td><td align="right" rowspan="1" colspan="1">6 (1–54)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> <6 month</td><td align="right" rowspan="1" colspan="1">28 (42)</td><td align="right" rowspan="1" colspan="1">66 (51)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ≥6 month</td><td align="right" rowspan="1" colspan="1">15 (22)</td><td align="right" rowspan="1" colspan="1">18 (14)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> TKI not given or unknown</td><td align="right" rowspan="1" colspan="1">24 (36)</td><td align="right" rowspan="1" colspan="1">48 (36)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Conditioning regimen</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" rowspan="1" colspan="1"> MAC</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> TBI>500 cGy single dose or > 800cGy</td><td align="right" rowspan="1" colspan="1">0</td><td align="right" rowspan="1" colspan="1">108 (83)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Busulfan > 9 mg/kg + other</td><td align="right" rowspan="1" colspan="1">0</td><td align="right" rowspan="1" colspan="1">22 (17)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> RIC (includes non-myeloablative)</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Melphalan ≤ 150 mg/m<sup>2</sup></td><td align="right" rowspan="1" colspan="1">24 (36)</td><td align="right" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Busulfan ≤ 9 mg/kg</td><td align="right" rowspan="1" colspan="1">20 (30)</td><td align="right" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> TBI ≤ 200 cGy dose<xref ref-type="table-fn" rid="TFN3">#</xref></td><td align="right" rowspan="1" colspan="1">18 (26)</td><td align="right" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Fludarabine + other</td><td align="right" rowspan="1" colspan="1">5 (7)</td><td align="right" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Total body irradiation</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">N/A</td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="right" rowspan="1" colspan="1">45 (67)</td><td align="right" rowspan="1" colspan="1">22 (17)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="right" rowspan="1" colspan="1">21 (31)</td><td align="right" rowspan="1" colspan="1">108 (83)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">1 (1)</td><td align="right" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Type of donor</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.10</td></tr><tr><td align="left" rowspan="1" colspan="1"> HLA - identical sibling</td><td align="right" rowspan="1" colspan="1">26 (39)</td><td align="right" rowspan="1" colspan="1">50 (38)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Well - matched URD</td><td align="right" rowspan="1" colspan="1">28 (42)</td><td align="right" rowspan="1" colspan="1">54 (42)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Partially – matched/ mismatched URD</td><td align="right" rowspan="1" colspan="1">5 (7)</td><td align="right" rowspan="1" colspan="1">21 (16)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> URD (matching unknown)</td><td align="right" rowspan="1" colspan="1">8 (12)</td><td align="right" rowspan="1" colspan="1">5 (4)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Donor –Recipient sex match</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.79</td></tr><tr><td align="left" rowspan="1" colspan="1"> Male-Male</td><td align="right" rowspan="1" colspan="1">22 (33)</td><td align="right" rowspan="1" colspan="1">47 (36)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Male-Female</td><td align="right" rowspan="1" colspan="1">18 (27)</td><td align="right" rowspan="1" colspan="1">40 (31)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Female-Male</td><td align="right" rowspan="1" colspan="1">15 (22)</td><td align="right" rowspan="1" colspan="1">24 (18)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Female-Female</td><td align="right" rowspan="1" colspan="1">12 (18)</td><td align="right" rowspan="1" colspan="1">18 (14)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">0</td><td align="right" rowspan="1" colspan="1">1 (<1)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Donor-Recipient CMV match</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.55</td></tr><tr><td align="left" rowspan="1" colspan="1"> Donor positive/Recipient positive</td><td align="right" rowspan="1" colspan="1">27 (40)</td><td align="right" rowspan="1" colspan="1">39 (30)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Donor positive/Recipient negative</td><td align="right" rowspan="1" colspan="1">9 (13)</td><td align="right" rowspan="1" colspan="1">15 (12)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Donor negative/Recipient positive</td><td align="right" rowspan="1" colspan="1">14 (21)</td><td align="right" rowspan="1" colspan="1">35 (27)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Donor negative/Recipient negative</td><td align="right" rowspan="1" colspan="1">15 (22)</td><td align="right" rowspan="1" colspan="1">38 (29)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Missing</td><td align="right" rowspan="1" colspan="1">2 (3)</td><td align="right" rowspan="1" colspan="1">3 (2)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Graft type</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.12</td></tr><tr><td align="left" rowspan="1" colspan="1"> Bone marrow</td><td align="right" rowspan="1" colspan="1">15 (22)</td><td align="right" rowspan="1" colspan="1">43 (33)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Peripheral blood</td><td align="right" rowspan="1" colspan="1">52 (78)</td><td align="right" rowspan="1" colspan="1">87 (67)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Year of transplant</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.53</td></tr><tr><td align="left" rowspan="1" colspan="1"> 2001–2004</td><td align="right" rowspan="1" colspan="1">40 (59)</td><td align="right" rowspan="1" colspan="1">70 (54)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> 2005–2009</td><td align="right" rowspan="1" colspan="1">27 (41)</td><td align="right" rowspan="1" colspan="1">60 (46)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">GVHD prophylaxis</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.36</td></tr><tr><td align="left" rowspan="1" colspan="1"> Tacrolimus ± other</td><td align="right" rowspan="1" colspan="1">61 (46)</td><td align="right" rowspan="1" colspan="1">72 (58)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Cyclosporine ± other</td><td align="right" rowspan="1" colspan="1">30 (45)</td><td align="right" rowspan="1" colspan="1">47 (36)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ATG/alemtuzumab</td><td align="right" rowspan="1" colspan="1">25 (37)</td><td align="right" rowspan="1" colspan="1">23 (17)</td><td align="center" rowspan="1" colspan="1">0.032</td></tr><tr><td align="left" rowspan="1" colspan="1"> Other</td><td align="right" rowspan="1" colspan="1">6 (8)</td><td align="right" rowspan="1" colspan="1">9 (7)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Median follow-up of survivors: months (range)</td><td align="right" rowspan="1" colspan="1">49 (3–108)</td><td align="right" rowspan="1" colspan="1">61 (3–119)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Post-transplant therapy</bold></td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Any TKI given as maintenance post-HCT</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.02</td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="right" rowspan="1" colspan="1">46 (69)</td><td align="right" rowspan="1" colspan="1">108 (83)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="right" rowspan="1" colspan="1">21 (31)</td><td align="right" rowspan="1" colspan="1">22 (17)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Duration of TKI given for maintenance post-HCT</td><td align="right" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">0.05</td></tr><tr><td align="left" rowspan="1" colspan="1"> < 3 months</td><td align="right" rowspan="1" colspan="1">7 (10)</td><td align="right" rowspan="1" colspan="1">4 (3)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> 3–12 months</td><td align="right" rowspan="1" colspan="1">9 (13)</td><td align="right" rowspan="1" colspan="1">9 (7)</td><td align="center" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ≤ 12 months</td><td align="right" rowspan="1" colspan="1">4 (6)</td><td align="right" rowspan="1" colspan="1">9 (7)</td><td align="center" rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><label>*</label><p id="P38">Includes both FISH and/or BCR/ABL PCR positive,</p></fn><fn id="TFN2"><label>**</label><p id="P39">Includes FISH negative and BCR/ABL PCR negative or missing,</p></fn><fn id="TFN3"><label>#</label><p id="P40">one patient received TBI <500 cGy single dose</p></fn><fn id="TFN4" fn-type="abbr"><p id="P41">Abbreviations: ALL acute lymphoblastic leukemia, RIC reduced intensity conditioning, MAC myeloablative conditioning, HCT hematopoietic cell transplantation, MRD minimal residual disease, TKI tyrosine kinase inhibitor, CMV cytomegalovirus, TBI total body irradiation, GVHD graft versus host disease,</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><p id="P42">Outcomes after HCT: Univariate analysis</p></caption><table frame="below" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th colspan="2" align="center" valign="bottom" rowspan="1">RIC</th><th colspan="2" align="center" valign="bottom" rowspan="1">MAC</th><th align="center" rowspan="1" colspan="1">P-value</th></tr><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1">N Eval</th><th align="center" rowspan="1" colspan="1">Prob (95% CI)</th><th align="center" rowspan="1" colspan="1">N Eval</th><th align="center" rowspan="1" colspan="1">Prob (95% CI)</th><th align="center" rowspan="1" colspan="1"></th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Relapse</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">130</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"> 3-year</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">49 (37–61)%</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">28 (20–36)%</td><td align="center" rowspan="1" colspan="1">0.058</td></tr><tr><td align="left" rowspan="1" colspan="1">Treatment related mortality</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">130</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"> 1-year</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">13 (6–23)%</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">36 (28–44)%</td><td align="center" rowspan="1" colspan="1"><0.001</td></tr><tr><td align="left" rowspan="1" colspan="1">Disease free survival</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">130</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"> 3-year</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">26 (16–37)%</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">28 (20–36)%</td><td align="center" rowspan="1" colspan="1">0.75</td></tr><tr><td align="left" rowspan="1" colspan="1">Overall survival</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">130</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"> 3-year</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">39 (27–52)%</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">35 (27–44)%</td><td align="center" rowspan="1" colspan="1">0.62</td></tr><tr><td align="left" rowspan="1" colspan="1">Acute GVHD, grade II – IV</td><td align="center" rowspan="1" colspan="1">66</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">130</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"> 100-day</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">30 (20–42)%</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">47 (39–56)%</td><td align="center" rowspan="1" colspan="1">0.014</td></tr><tr><td align="left" rowspan="1" colspan="1">Chronic GVHD at 3 years</td><td align="center" rowspan="1" colspan="1">66</td><td align="center" rowspan="1" colspan="1">60 (47–72)%</td><td align="center" rowspan="1" colspan="1">128</td><td align="center" rowspan="1" colspan="1">47 (38–56)%</td><td align="center" rowspan="1" colspan="1">0.17</td></tr></tbody></table></table-wrap><table-wrap id="T3" position="float" orientation="portrait"><label>Table 3</label><caption><p id="P43">Multivariate analysis of acute GVHD, chronic GVHD, treatment related mortality, relapse, disease free survival and overall survival</p></caption><table frame="box" rules="all"><thead><tr><th align="left" rowspan="1" colspan="1">Outcomes</th><th align="center" rowspan="1" colspan="1">N</th><th align="center" rowspan="1" colspan="1">HR (95% CI)</th><th align="right" rowspan="1" colspan="1">P-value</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1"><bold>Acute GVHD:</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Main effect:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Myeloablative conditioning</td><td align="center" rowspan="1" colspan="1">130</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Reduced intensity conditioning</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1">0.54 (0.33–0.88)</td><td align="right" rowspan="1" colspan="1">0.014</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Chronic GVHD:</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Main effect:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Myeloablative conditioning</td><td align="center" rowspan="1" colspan="1">130</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Reduced intensity conditioning</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1">1.23 (0.81–1.86)</td><td align="right" rowspan="1" colspan="1">0.34</td></tr><tr><td align="left" rowspan="1" colspan="1">Other factors:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Pre HCT TKI</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">153</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">44</td><td align="center" rowspan="1" colspan="1">0.88 (0.53–1.45)</td><td align="right" rowspan="1" colspan="1">0.62</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Treatment related mortality:</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Main effect:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Myeloablative conditioning</td><td align="center" rowspan="1" colspan="1">130</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Reduced intensity conditioning</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1">0.60 (0.35–1.02)</td><td align="right" rowspan="1" colspan="1">0.059</td></tr><tr><td align="left" rowspan="1" colspan="1">Other factors:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Age</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ≤ 40 years</td><td align="center" rowspan="1" colspan="1">42</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> > 40</td><td align="center" rowspan="1" colspan="1">155</td><td align="center" rowspan="1" colspan="1">3.24 (1.45–7.24)</td><td align="right" rowspan="1" colspan="1">0.0042</td></tr><tr><td align="left" rowspan="1" colspan="1">Minimal residual disease*</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>neg</sup></td><td align="center" rowspan="1" colspan="1">84</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1">P<sub>overall</sub>=0.33</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>pos</sup></td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">0.72 (0.45–1.16)</td><td align="right" rowspan="1" colspan="1">0.18</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD unknown</td><td align="center" rowspan="1" colspan="1">12</td><td align="center" rowspan="1" colspan="1">0.65 (0.25–1.69)</td><td align="right" rowspan="1" colspan="1">0.37</td></tr><tr><td align="left" rowspan="1" colspan="1">Pre-HCT TKI</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">153</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">44</td><td align="center" rowspan="1" colspan="1">0.66 (0.38–1.15)</td><td align="right" rowspan="1" colspan="1">0.14</td></tr><tr><td align="left" rowspan="1" colspan="1">Chronic GVHD (time dependent)</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">96</td><td align="center" rowspan="1" colspan="1">1.74 (0.97–3.11)</td><td align="right" rowspan="1" colspan="1">0.064</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Relapse:</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Main effect:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Myeloablative conditioning</td><td align="center" rowspan="1" colspan="1">130</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Reduced intensity conditioning</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1">1.84 (1.15–2.94)</td><td align="right" rowspan="1" colspan="1">0.011</td></tr><tr><td align="left" rowspan="1" colspan="1">Other factors:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Age</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ≤ 40 years</td><td align="center" rowspan="1" colspan="1">42</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> > 40</td><td align="center" rowspan="1" colspan="1">155</td><td align="center" rowspan="1" colspan="1">1.02 (0.61–1.68)</td><td align="right" rowspan="1" colspan="1">0.95</td></tr><tr><td align="left" rowspan="1" colspan="1">Minimal residual disease*</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>neg</sup></td><td align="center" rowspan="1" colspan="1">84</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1">P<sub>overall</sub>=0.13</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>pos</sup></td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">1.60 (0.96–2.67)</td><td align="right" rowspan="1" colspan="1">0.070</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD unknown</td><td align="center" rowspan="1" colspan="1">12</td><td align="center" rowspan="1" colspan="1">0.77 (0.22–2.78)</td><td align="right" rowspan="1" colspan="1">0.69</td></tr><tr><td align="left" rowspan="1" colspan="1">Pre-HCT TKI</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">153</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">44</td><td align="center" rowspan="1" colspan="1">1.88 (1.11–3.17)</td><td align="right" rowspan="1" colspan="1">0.018</td></tr><tr><td align="left" rowspan="1" colspan="1">Chronic GVHD (time dependent)</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">96</td><td align="center" rowspan="1" colspan="1">0.72 (0.40–1.31)</td><td align="right" rowspan="1" colspan="1">0.28</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Disease free survival:</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Main effect:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Myeloablative conditioning</td><td align="center" rowspan="1" colspan="1">130</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Reduced intensity conditioning</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1">1.08 (0.76–1.51)</td><td align="right" rowspan="1" colspan="1">0.68</td></tr><tr><td align="left" rowspan="1" colspan="1">Other factors:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Age</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ≤ 40 years</td><td align="center" rowspan="1" colspan="1">42</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> > 40</td><td align="center" rowspan="1" colspan="1">155</td><td align="center" rowspan="1" colspan="1">1.68 (1.11–2.56)</td><td align="right" rowspan="1" colspan="1">0.015</td></tr><tr><td align="left" rowspan="1" colspan="1">Minimal residual disease*</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>neg</sup></td><td align="center" rowspan="1" colspan="1">84</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1">P<sub>overall</sub>=0.56</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>pos</sup></td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">1.06 (0.75–1.48)</td><td align="right" rowspan="1" colspan="1">0.75</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD unknown</td><td align="center" rowspan="1" colspan="1">12</td><td align="center" rowspan="1" colspan="1">0.67 (0.29–1.54)</td><td align="right" rowspan="1" colspan="1">0.35</td></tr><tr><td align="left" rowspan="1" colspan="1">Pre-HCT TKI</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">153</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">44</td><td align="center" rowspan="1" colspan="1">1.08 (0.75–1.54)</td><td align="right" rowspan="1" colspan="1">0.69</td></tr><tr><td align="left" rowspan="1" colspan="1">Chronic GVHD (time dependent)</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">96</td><td align="center" rowspan="1" colspan="1">1.02 (0.68–1.54)</td><td align="right" rowspan="1" colspan="1">0.92</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Overall survival:</bold></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Main effect:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Myeloablative conditioning</td><td align="center" rowspan="1" colspan="1">130</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Reduced intensity conditioning</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1">0.85 (0.59–1.24)</td><td align="right" rowspan="1" colspan="1">0.41</td></tr><tr><td align="left" rowspan="1" colspan="1">Other factors:</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Age</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> ≤ 40 years</td><td align="center" rowspan="1" colspan="1">42</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> > 40</td><td align="center" rowspan="1" colspan="1">155</td><td align="center" rowspan="1" colspan="1">1.90 (1.19–3.04)</td><td align="right" rowspan="1" colspan="1">0.0070</td></tr><tr><td align="left" rowspan="1" colspan="1">Minimal residual disease*</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>neg</sup></td><td align="center" rowspan="1" colspan="1">84</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1">P<sub>overall</sub>=0.66</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD<sup>pos</sup></td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">0.94 (0.65–1.34)</td><td align="right" rowspan="1" colspan="1">0.71</td></tr><tr><td align="left" rowspan="1" colspan="1"> MRD unknown</td><td align="center" rowspan="1" colspan="1">12</td><td align="center" rowspan="1" colspan="1">0.67 (0.28–1.62)</td><td align="right" rowspan="1" colspan="1">0.37</td></tr><tr><td align="left" rowspan="1" colspan="1">Pre-HCT TKI</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">153</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">44</td><td align="center" rowspan="1" colspan="1">1.01 (0.69–1.48)</td><td align="right" rowspan="1" colspan="1">0.96</td></tr><tr><td align="left" rowspan="1" colspan="1">Chronic GVHD (time dependent)</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> No</td><td align="center" rowspan="1" colspan="1">101</td><td align="center" rowspan="1" colspan="1">1.00</td><td align="right" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Yes</td><td align="center" rowspan="1" colspan="1">96</td><td align="center" rowspan="1" colspan="1">1.15 (0.77–1.74)</td><td align="right" rowspan="1" colspan="1">0.49</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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