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Leukemia. 2014 Mar;28(3):658-65. doi: 10.1038/leu.2013.253. Epub 2013 Aug 30.

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.

Author information

1
Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA.
2
Bristol Adult BMT Unit, Bristol Children's Hospital, Bristol, UK.
3
Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA.
4
Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA.
5
Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
6
Winship Cancer Institute, Emory University, Atlanta, GA, USA.
7
Department of Hematology and Oncology, University of Chicago Medicine, Chicago, IL, USA.
8
Klinik und Poliklinik fur Stammzelltransplantation, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany.
9
Department of Hematology, University Hospital, Grenoble, France.
10
Department of Bone Marrow Transplantation, Massachusetts General Hospital, Boston, MA, USA.
11
Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.
12
Medical College of Wisconsin, Milwaukee, WI, USA.
13
Imperial College, Section of Hematology, Division of Experimental Medicine, Department of Medicine, London, UK.
14
Department of Hematology and Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.
15
Princess Margaret Hospital, Toronto, Ontario, Canada.
16
Department of Pediatric Hematology and Oncology, All Children's Hospital, St Petersburg, FL, USA.
17
Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA.
18
Department of Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital/SA Pathology, Adelaide, South Australia, Australia.
19
Department of Hematology and Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.
20
Department of Hematology and Oncology, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY, USA.
21
Department of Hematology and Internal Medicine, Mayo Clinic Rochester, Rochester, MN, USA.
22
Department of Hematology and Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
23
Department of Oncology, Baylor University Medical Center, Dallas, TX, USA.
24
Department of Hematology and Oncology, Shands HealthCare and University of Florida, Gainesville, FL, USA.
25
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA.
26
Department of Hematology, Rambam Medical Center, Haifa, Israel.
27
Department of Bone Marrow Transplantation and Leukemia, Barnes Jewish Hospital, Washington University School of Medicine, St Louis, MO, USA.
28
Bone Marrow and Stem Cell Transplant Center, Emory University Hospital, Atlanta, GA, USA.
29
Our Lady of Mercy Medical Center, Bronx, NY, USA.

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.

PMID:
23989431
PMCID:
PMC3951192
DOI:
10.1038/leu.2013.253
[Indexed for MEDLINE]
Free PMC Article

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