title: Outcomes of human leukocyte antigen-matched sibling donor hematopoietic cell transplantation in chronic lymphocytic leukemia: myeloablative versus reduced-intensity conditioning regimens.
abstract: Allogeneic hematopoietic cell transplantation (HCT) can cure some chronic lymphocytic leukemia (CLL) subjects. This study compared outcomes of myeloablative (MA) and reduced-intensity conditioning (RIC) transplants from HLA-matched sibling donors (MSD) for CLL. From 1995 to 2007, information regarding 297 CLL subjects was reported to the Center of International Blood and Marrow Transplant Research; of these, 163 underwent MA and 134 underwent RIC MSD HCT. The MA subjects underwent transplantation less often after 2000 and less commonly received antithymocyte globulin (4% versus 13%, P = .004) or prior antibody therapy (14% versus 53%; P < .001). RIC was associated with a greater likelihood of platelet recovery and less grade 2 to 4 acute graft-versus-host disease compared with MA conditioning. One- and 5-year treatment-related mortality (TRM) were 24% (95% confidence intervals [CI], 16% to 33%) versus 37% (95% CI, 30% to 45%; P = .023), and 40% (95% CI, 29% to 51%) versus 54% (95% CI, 46% to 62%; P = .036), respectively, and the relapse/progression rates at 1 and 5 years were 21% (95% CI, 14% to 29%) versus 10% (95% CI, 6% to 15%; P = .020), and 35% (95% CI, 26% to 46%) versus 17% (95% CI, 12% to 24%; P = .003), respectively. MA conditioning was associated with better progression-free (PFS) (relative risk, .60; 95% CI, .37 to .97; P = .038) and 3-year survival in transplantations before 2001, but for subsequent years, RIC was associated with better PFS and survival (relative risk, 1.49 [95% CI, .92 to 2.42]; P = .10; and relative risk, 1.86 [95% CI, 1.11 to 3.13]; P = .019). Pretransplantation disease status was the most important predictor of relapse (P = .003) and PFS (P = .0007) for both forms of transplantation conditioning. MA and RIC MSD transplantations are effective for CLL. Future strategies to decrease TRM and reduce relapses are warranted.
authors.affiliation: Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: sobeckr@ccf.org.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Sobecks
authors.affiliation: Department of Hematology/Oncology, Mayo Clinic Arizona, Phoenix, Arizona; Phoenix Children's Hospital, Phoenix, Arizona.
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.affiliation: Division of Experimental Medicine, Department of Medicine, Hematology Research Centre, Imperial College London, London, United Kingdom.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Ahn
authors.affiliation: Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Divison of Hematology, Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Sabloff
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Department of Hematology/Oncology, All Children's Hospital, St. Petersburg, Florida.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia.
authors.forename: Mahmoud D
authors.initials: MD
authors.lastname: Aljurf
authors.affiliation: Department of Hematology/Oncology, Baylor College of Medicine, Center for Cell and Gene Therapy, Houston, Texas.
authors.forename: Rammurti T
authors.initials: RT
authors.lastname: Kamble
authors.affiliation: Division of Hematology & Oncology, Department of Medicine, Shands HealthCare and University of Florida, Gainesville, Florida.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Hsu
authors.affiliation: National Institutes of Health-National Cancer Institute Experimental Transplantation and Immunology Branch, Bethesda, Maryland.
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
authors.affiliation: Stony Brook University Medical Center, Stony Brook, New York.
authors.forename: Baldeep
authors.initials: B
authors.lastname: Wirk
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Seftel
authors.affiliation: Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Lewis
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.affiliation: Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Matt E
authors.initials: ME
authors.lastname: Kalaycio
authors.affiliation: Center for Hematologic Malignancies, Oregon Health and Science University, Portland, Oregon.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.affiliation: Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
mesh_terms: D000328:Adult; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D035781:Siblings; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens
keywords: Chronic lymphocytic leukemia; Myeloablative allogeneic hematopoietic cell transplantation; Outcomes; Reduced-intensity conditioning