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.
Identifieur interne : 003927 ( PubMed/Corpus ); précédent : 003926; suivant : 003928Ph+ 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.
Auteurs : V. Bachanova ; D I Marks ; M-J Zhang ; H. Wang ; M. De Lima ; M D Aljurf ; M. Arellano ; A S Artz ; U. Bacher ; J-Y Cahn ; Y-B Chen ; E A Copelan ; W R Drobyski ; R P Gale ; J P Greer ; V. Gupta ; G A Hale ; P. Kebriaei ; H M Lazarus ; I D Lewis ; V A Lewis ; J L Liesveld ; M R Litzow ; A W Loren ; A M Miller ; M. Norkin ; B. Oran ; J. Pidala ; J M Rowe ; B N Savani ; W. Saber ; R. Vij ; E K Waller ; P H Wiernik ; D J WeisdorfSource :
- Leukemia [ 1476-5551 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Animals, Bone Marrow Transplantation, Female, Guinea Pigs, Humans, Male, Middle Aged, Neoplasm, Residual, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology), Precursor Cell Lymphoblastic Leukemia-Lymphoma (surgery), Protein-Tyrosine Kinases (antagonists & inhibitors), Remission Induction, Survival Rate, Transplantation Conditioning, Transplantation, Homologous, Young Adult.
- MESH :
- chemical , antagonists & inhibitors : Protein-Tyrosine Kinases.
- pathology : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- surgery : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- Adult, Animals, Bone Marrow Transplantation, Female, Guinea Pigs, Humans, Male, Middle Aged, Neoplasm, Residual, Philadelphia Chromosome, Remission Induction, Survival Rate, Transplantation Conditioning, Transplantation, Homologous, Young Adult.
Abstract
The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (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 (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) 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 (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (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 with a similar MRD 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(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.
DOI: 10.1038/leu.2013.253
PubMed: 23989431
Links to Exploration step
pubmed:23989431Le document en format XML
<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, V" sort="Bachanova, V" uniqKey="Bachanova V" first="V" last="Bachanova">V. Bachanova</name>
<affiliation><nlm:affiliation>Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Marks, D I" sort="Marks, D I" uniqKey="Marks D" first="D I" last="Marks">D I Marks</name>
<affiliation><nlm:affiliation>Bristol Adult BMT Unit, Bristol Children's Hospital, Bristol, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhang, M J" sort="Zhang, M J" uniqKey="Zhang M" first="M-J" last="Zhang">M-J Zhang</name>
<affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wang, H" sort="Wang, H" uniqKey="Wang H" first="H" last="Wang">H. Wang</name>
<affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="De Lima, M" sort="De Lima, M" uniqKey="De Lima M" first="M" last="De Lima">M. De Lima</name>
<affiliation><nlm:affiliation>Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Aljurf, M D" sort="Aljurf, M D" uniqKey="Aljurf M" first="M D" last="Aljurf">M D Aljurf</name>
<affiliation><nlm:affiliation>Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Arellano, M" sort="Arellano, M" uniqKey="Arellano M" first="M" last="Arellano">M. Arellano</name>
<affiliation><nlm:affiliation>Winship Cancer Institute, Emory University, Atlanta, GA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Artz, A S" sort="Artz, A S" uniqKey="Artz A" first="A S" last="Artz">A S Artz</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, University of Chicago Medicine, Chicago, IL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bacher, U" sort="Bacher, U" uniqKey="Bacher U" first="U" last="Bacher">U. Bacher</name>
<affiliation><nlm:affiliation>Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cahn, J Y" sort="Cahn, J Y" uniqKey="Cahn J" first="J-Y" last="Cahn">J-Y Cahn</name>
<affiliation><nlm:affiliation>Department of Hematology, University Hospital, Grenoble, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Chen, Y B" sort="Chen, Y B" uniqKey="Chen Y" first="Y-B" last="Chen">Y-B Chen</name>
<affiliation><nlm:affiliation>Department of Bone Marrow Transplantation, Massachusetts General Hospital, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Copelan, E A" sort="Copelan, E A" uniqKey="Copelan E" first="E A" last="Copelan">E A Copelan</name>
<affiliation><nlm:affiliation>Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Drobyski, W R" sort="Drobyski, W R" uniqKey="Drobyski W" first="W R" last="Drobyski">W R Drobyski</name>
<affiliation><nlm:affiliation>Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gale, R P" sort="Gale, R P" uniqKey="Gale R" first="R P" last="Gale">R P Gale</name>
<affiliation><nlm:affiliation>Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Greer, J P" sort="Greer, J P" uniqKey="Greer J" first="J P" last="Greer">J P Greer</name>
<affiliation><nlm:affiliation>Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gupta, V" sort="Gupta, V" uniqKey="Gupta V" first="V" last="Gupta">V. Gupta</name>
<affiliation><nlm:affiliation>Princess Margaret Hospital, Toronto, Ontario, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hale, G A" sort="Hale, G A" uniqKey="Hale G" first="G A" last="Hale">G A Hale</name>
<affiliation><nlm:affiliation>Department of Pediatric Hematology and Oncology, All Children's Hospital, St Petersburg, FL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kebriaei, P" sort="Kebriaei, P" uniqKey="Kebriaei P" first="P" last="Kebriaei">P. Kebriaei</name>
<affiliation><nlm:affiliation>Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lazarus, H M" sort="Lazarus, H M" uniqKey="Lazarus H" first="H M" last="Lazarus">H M Lazarus</name>
<affiliation><nlm:affiliation>Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lewis, I D" sort="Lewis, I D" uniqKey="Lewis I" first="I D" last="Lewis">I D Lewis</name>
<affiliation><nlm:affiliation>Department of Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, South Australia, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lewis, V A" sort="Lewis, V A" uniqKey="Lewis V" first="V A" last="Lewis">V A Lewis</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Liesveld, J L" sort="Liesveld, J L" uniqKey="Liesveld J" first="J L" last="Liesveld">J L Liesveld</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Litzow, M R" sort="Litzow, M R" uniqKey="Litzow M" first="M R" last="Litzow">M R Litzow</name>
<affiliation><nlm:affiliation>Department of Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Loren, A W" sort="Loren, A W" uniqKey="Loren A" first="A W" last="Loren">A W Loren</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Miller, A M" sort="Miller, A M" uniqKey="Miller A" first="A M" last="Miller">A M Miller</name>
<affiliation><nlm:affiliation>Department of Oncology, Baylor University Medical Center, Dallas, TX, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Norkin, M" sort="Norkin, M" uniqKey="Norkin M" first="M" last="Norkin">M. Norkin</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Shands HealthCare and University of Florida, Gainesville, FL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Oran, B" sort="Oran, B" uniqKey="Oran B" first="B" last="Oran">B. Oran</name>
<affiliation><nlm:affiliation>Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Pidala, J" sort="Pidala, J" uniqKey="Pidala J" first="J" last="Pidala">J. Pidala</name>
<affiliation><nlm:affiliation>Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rowe, J M" sort="Rowe, J M" uniqKey="Rowe J" first="J M" last="Rowe">J M Rowe</name>
<affiliation><nlm:affiliation>Department of Hematology, Rambam Medical Center, Haifa, Israel.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Savani, B N" sort="Savani, B N" uniqKey="Savani B" first="B N" last="Savani">B N Savani</name>
<affiliation><nlm:affiliation>Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Saber, W" sort="Saber, W" uniqKey="Saber W" first="W" last="Saber">W. Saber</name>
<affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Vij, R" sort="Vij, R" uniqKey="Vij R" first="R" last="Vij">R. Vij</name>
<affiliation><nlm:affiliation>Department of Bone Marrow Transplantation and Leukemia, Barnes Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Waller, E K" sort="Waller, E K" uniqKey="Waller E" first="E K" last="Waller">E K Waller</name>
<affiliation><nlm:affiliation>Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wiernik, P H" sort="Wiernik, P H" uniqKey="Wiernik P" first="P H" last="Wiernik">P H Wiernik</name>
<affiliation><nlm:affiliation>Our Lady of Mercy Medical Center, Bronx, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weisdorf, D J" sort="Weisdorf, D J" uniqKey="Weisdorf D" first="D J" last="Weisdorf">D J Weisdorf</name>
<affiliation><nlm:affiliation>Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.</nlm:affiliation>
</affiliation>
</author>
</titleStmt>
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<sourceDesc><biblStruct><analytic><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, V" sort="Bachanova, V" uniqKey="Bachanova V" first="V" last="Bachanova">V. Bachanova</name>
<affiliation><nlm:affiliation>Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Marks, D I" sort="Marks, D I" uniqKey="Marks D" first="D I" last="Marks">D I Marks</name>
<affiliation><nlm:affiliation>Bristol Adult BMT Unit, Bristol Children's Hospital, Bristol, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhang, M J" sort="Zhang, M J" uniqKey="Zhang M" first="M-J" last="Zhang">M-J Zhang</name>
<affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wang, H" sort="Wang, H" uniqKey="Wang H" first="H" last="Wang">H. Wang</name>
<affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="De Lima, M" sort="De Lima, M" uniqKey="De Lima M" first="M" last="De Lima">M. De Lima</name>
<affiliation><nlm:affiliation>Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Aljurf, M D" sort="Aljurf, M D" uniqKey="Aljurf M" first="M D" last="Aljurf">M D Aljurf</name>
<affiliation><nlm:affiliation>Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Arellano, M" sort="Arellano, M" uniqKey="Arellano M" first="M" last="Arellano">M. Arellano</name>
<affiliation><nlm:affiliation>Winship Cancer Institute, Emory University, Atlanta, GA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Artz, A S" sort="Artz, A S" uniqKey="Artz A" first="A S" last="Artz">A S Artz</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, University of Chicago Medicine, Chicago, IL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bacher, U" sort="Bacher, U" uniqKey="Bacher U" first="U" last="Bacher">U. Bacher</name>
<affiliation><nlm:affiliation>Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Cahn, J Y" sort="Cahn, J Y" uniqKey="Cahn J" first="J-Y" last="Cahn">J-Y Cahn</name>
<affiliation><nlm:affiliation>Department of Hematology, University Hospital, Grenoble, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Chen, Y B" sort="Chen, Y B" uniqKey="Chen Y" first="Y-B" last="Chen">Y-B Chen</name>
<affiliation><nlm:affiliation>Department of Bone Marrow Transplantation, Massachusetts General Hospital, Boston, MA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Copelan, E A" sort="Copelan, E A" uniqKey="Copelan E" first="E A" last="Copelan">E A Copelan</name>
<affiliation><nlm:affiliation>Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Drobyski, W R" sort="Drobyski, W R" uniqKey="Drobyski W" first="W R" last="Drobyski">W R Drobyski</name>
<affiliation><nlm:affiliation>Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gale, R P" sort="Gale, R P" uniqKey="Gale R" first="R P" last="Gale">R P Gale</name>
<affiliation><nlm:affiliation>Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Greer, J P" sort="Greer, J P" uniqKey="Greer J" first="J P" last="Greer">J P Greer</name>
<affiliation><nlm:affiliation>Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gupta, V" sort="Gupta, V" uniqKey="Gupta V" first="V" last="Gupta">V. Gupta</name>
<affiliation><nlm:affiliation>Princess Margaret Hospital, Toronto, Ontario, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hale, G A" sort="Hale, G A" uniqKey="Hale G" first="G A" last="Hale">G A Hale</name>
<affiliation><nlm:affiliation>Department of Pediatric Hematology and Oncology, All Children's Hospital, St Petersburg, FL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Kebriaei, P" sort="Kebriaei, P" uniqKey="Kebriaei P" first="P" last="Kebriaei">P. Kebriaei</name>
<affiliation><nlm:affiliation>Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lazarus, H M" sort="Lazarus, H M" uniqKey="Lazarus H" first="H M" last="Lazarus">H M Lazarus</name>
<affiliation><nlm:affiliation>Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lewis, I D" sort="Lewis, I D" uniqKey="Lewis I" first="I D" last="Lewis">I D Lewis</name>
<affiliation><nlm:affiliation>Department of Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, South Australia, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lewis, V A" sort="Lewis, V A" uniqKey="Lewis V" first="V A" last="Lewis">V A Lewis</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Liesveld, J L" sort="Liesveld, J L" uniqKey="Liesveld J" first="J L" last="Liesveld">J L Liesveld</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Litzow, M R" sort="Litzow, M R" uniqKey="Litzow M" first="M R" last="Litzow">M R Litzow</name>
<affiliation><nlm:affiliation>Department of Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Loren, A W" sort="Loren, A W" uniqKey="Loren A" first="A W" last="Loren">A W Loren</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Miller, A M" sort="Miller, A M" uniqKey="Miller A" first="A M" last="Miller">A M Miller</name>
<affiliation><nlm:affiliation>Department of Oncology, Baylor University Medical Center, Dallas, TX, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Norkin, M" sort="Norkin, M" uniqKey="Norkin M" first="M" last="Norkin">M. Norkin</name>
<affiliation><nlm:affiliation>Department of Hematology and Oncology, Shands HealthCare and University of Florida, Gainesville, FL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Oran, B" sort="Oran, B" uniqKey="Oran B" first="B" last="Oran">B. Oran</name>
<affiliation><nlm:affiliation>Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Pidala, J" sort="Pidala, J" uniqKey="Pidala J" first="J" last="Pidala">J. Pidala</name>
<affiliation><nlm:affiliation>Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rowe, J M" sort="Rowe, J M" uniqKey="Rowe J" first="J M" last="Rowe">J M Rowe</name>
<affiliation><nlm:affiliation>Department of Hematology, Rambam Medical Center, Haifa, Israel.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Savani, B N" sort="Savani, B N" uniqKey="Savani B" first="B N" last="Savani">B N Savani</name>
<affiliation><nlm:affiliation>Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Saber, W" sort="Saber, W" uniqKey="Saber W" first="W" last="Saber">W. Saber</name>
<affiliation><nlm:affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Vij, R" sort="Vij, R" uniqKey="Vij R" first="R" last="Vij">R. Vij</name>
<affiliation><nlm:affiliation>Department of Bone Marrow Transplantation and Leukemia, Barnes Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Waller, E K" sort="Waller, E K" uniqKey="Waller E" first="E K" last="Waller">E K Waller</name>
<affiliation><nlm:affiliation>Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wiernik, P H" sort="Wiernik, P H" uniqKey="Wiernik P" first="P H" last="Wiernik">P H Wiernik</name>
<affiliation><nlm:affiliation>Our Lady of Mercy Medical Center, Bronx, NY, USA.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weisdorf, D J" sort="Weisdorf, D J" uniqKey="Weisdorf D" first="D J" last="Weisdorf">D J Weisdorf</name>
<affiliation><nlm:affiliation>Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series><title level="j">Leukemia</title>
<idno type="eISSN">1476-5551</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
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<term>Animals</term>
<term>Bone Marrow Transplantation</term>
<term>Female</term>
<term>Guinea Pigs</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neoplasm, Residual</term>
<term>Philadelphia Chromosome</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (surgery)</term>
<term>Protein-Tyrosine Kinases (antagonists & inhibitors)</term>
<term>Remission Induction</term>
<term>Survival Rate</term>
<term>Transplantation Conditioning</term>
<term>Transplantation, Homologous</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Protein-Tyrosine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Animals</term>
<term>Bone Marrow Transplantation</term>
<term>Female</term>
<term>Guinea Pigs</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neoplasm, Residual</term>
<term>Philadelphia Chromosome</term>
<term>Remission Induction</term>
<term>Survival Rate</term>
<term>Transplantation Conditioning</term>
<term>Transplantation, Homologous</term>
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<front><div type="abstract" xml:lang="en">The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (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 (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) 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 (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (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 with a similar MRD 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(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23989431</PMID>
<DateCreated><Year>2014</Year>
<Month>03</Month>
<Day>05</Day>
</DateCreated>
<DateCompleted><Year>2014</Year>
<Month>04</Month>
<Day>30</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>11</Month>
<Day>11</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-5551</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>28</Volume>
<Issue>3</Issue>
<PubDate><Year>2014</Year>
<Month>Mar</Month>
</PubDate>
</JournalIssue>
<Title>Leukemia</Title>
<ISOAbbreviation>Leukemia</ISOAbbreviation>
</Journal>
<ArticleTitle>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.</ArticleTitle>
<Pagination><MedlinePgn>658-65</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/leu.2013.253</ELocationID>
<Abstract><AbstractText>The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (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 (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) 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 (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (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 with a similar MRD 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(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bachanova</LastName>
<ForeName>V</ForeName>
<Initials>V</Initials>
<Identifier Source="ORCID">000000029325432X</Identifier>
<AffiliationInfo><Affiliation>Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marks</LastName>
<ForeName>D I</ForeName>
<Initials>DI</Initials>
<AffiliationInfo><Affiliation>Bristol Adult BMT Unit, Bristol Children's Hospital, Bristol, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>M-J</ForeName>
<Initials>MJ</Initials>
<AffiliationInfo><Affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>H</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>de Lima</LastName>
<ForeName>M</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aljurf</LastName>
<ForeName>M D</ForeName>
<Initials>MD</Initials>
<AffiliationInfo><Affiliation>Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>M</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Winship Cancer Institute, Emory University, Atlanta, GA, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>A S</ForeName>
<Initials>AS</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Oncology, University of Chicago Medicine, Chicago, IL, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>U</ForeName>
<Initials>U</Initials>
<AffiliationInfo><Affiliation>Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cahn</LastName>
<ForeName>J-Y</ForeName>
<Initials>JY</Initials>
<AffiliationInfo><Affiliation>Department of Hematology, University Hospital, Grenoble, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Y-B</ForeName>
<Initials>YB</Initials>
<AffiliationInfo><Affiliation>Department of Bone Marrow Transplantation, Massachusetts General Hospital, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Copelan</LastName>
<ForeName>E A</ForeName>
<Initials>EA</Initials>
<AffiliationInfo><Affiliation>Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>W R</ForeName>
<Initials>WR</Initials>
<AffiliationInfo><Affiliation>Medical College of Wisconsin, Milwaukee, WI, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gale</LastName>
<ForeName>R P</ForeName>
<Initials>RP</Initials>
<AffiliationInfo><Affiliation>Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Greer</LastName>
<ForeName>J P</ForeName>
<Initials>JP</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gupta</LastName>
<ForeName>V</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Princess Margaret Hospital, Toronto, Ontario, Canada.</Affiliation>
</AffiliationInfo>
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<ForeName>G A</ForeName>
<Initials>GA</Initials>
<AffiliationInfo><Affiliation>Department of Pediatric Hematology and Oncology, All Children's Hospital, St Petersburg, FL, USA.</Affiliation>
</AffiliationInfo>
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<ForeName>P</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.</Affiliation>
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<ForeName>H M</ForeName>
<Initials>HM</Initials>
<AffiliationInfo><Affiliation>Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lewis</LastName>
<ForeName>I D</ForeName>
<Initials>ID</Initials>
<AffiliationInfo><Affiliation>Department of Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, South Australia, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lewis</LastName>
<ForeName>V A</ForeName>
<Initials>VA</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>J L</ForeName>
<Initials>JL</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Oncology, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Litzow</LastName>
<ForeName>M R</ForeName>
<Initials>MR</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Loren</LastName>
<ForeName>A W</ForeName>
<Initials>AW</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Miller</LastName>
<ForeName>A M</ForeName>
<Initials>AM</Initials>
<AffiliationInfo><Affiliation>Department of Oncology, Baylor University Medical Center, Dallas, TX, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Norkin</LastName>
<ForeName>M</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Oncology, Shands HealthCare and University of Florida, Gainesville, FL, USA.</Affiliation>
</AffiliationInfo>
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<ForeName>B</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.</Affiliation>
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<ForeName>J</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Rowe</LastName>
<ForeName>J M</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>Department of Hematology, Rambam Medical Center, Haifa, Israel.</Affiliation>
</AffiliationInfo>
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<ForeName>B N</ForeName>
<Initials>BN</Initials>
<AffiliationInfo><Affiliation>Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.</Affiliation>
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<Author ValidYN="Y"><LastName>Saber</LastName>
<ForeName>W</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Vij</LastName>
<ForeName>R</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Bone Marrow Transplantation and Leukemia, Barnes Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Waller</LastName>
<ForeName>E K</ForeName>
<Initials>EK</Initials>
<AffiliationInfo><Affiliation>Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA, USA.</Affiliation>
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<ForeName>P H</ForeName>
<Initials>PH</Initials>
<AffiliationInfo><Affiliation>Our Lady of Mercy Medical Center, Bronx, NY, USA.</Affiliation>
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<ForeName>D J</ForeName>
<Initials>DJ</Initials>
<AffiliationInfo><Affiliation>Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>U10 HL069294</GrantID>
<Acronym>HL</Acronym>
<Agency>NHLBI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 CA016672</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U24 CA076518</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>UL1 TR000114</GrantID>
<Acronym>TR</Acronym>
<Agency>NCATS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>KL2 TR000113</GrantID>
<Acronym>TR</Acronym>
<Agency>NCATS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2013</Year>
<Month>08</Month>
<Day>30</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Leukemia</MedlineTA>
<NlmUniqueID>8704895</NlmUniqueID>
<ISSNLinking>0887-6924</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber>
<NameOfSubstance UI="D011505">Protein-Tyrosine Kinases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016026" MajorTopicYN="Y">Bone Marrow Transplantation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
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