title: Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome.
abstract: Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34(+) dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 × 10(6) CD34(+)/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P = .001), overall mortality (HR, 1.48; P = .008), and lower neutrophil (odds ratio [OR], .76; P = .03) and platelet (OR, .76; P = .03) recovery. PBPC from unrelated donors with CD34(+) dose < 6 × 10(6) CD34(+)/kg was also associated with higher nonrelapse (HR, 1.38; P = .02) and overall mortality (HR, 1.20; P = .05). In contrast to reports after myeloablative HCT, CD34(+) dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34(+) doses >4 × 10(6) CD34(+)/kg and >6 × 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Törlén
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden; Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.affiliation: Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Le Rademacher
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Minoo
authors.initials: M
authors.lastname: Batiwalla
authors.affiliation: Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Junfang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tom
authors.initials: T
authors.lastname: Erkers
authors.affiliation: Department of Hematologic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ho
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.affiliation: Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Keever-Taylor
authors.affiliation: Division of Hematology/Oncology, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Tamila
authors.initials: T
authors.lastname: Kindwall-Keller
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Stem Cell Therapeutics Program, Novartis Pharmaceuticals Inc, East Hanover, New Jersey.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Laughlin
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Lill
authors.affiliation: Centre for Children's Cancer & Blood Disorders, Sydney Children's Hospital, Sydney, NSW, Australia.
authors.forename: Tracey
authors.initials: T
authors.lastname: O'Brien
authors.affiliation: Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Department of Clinical Haematology, Churchill Hospital, Oxford University Hospital, Oxford, United Kingdom.
authors.forename: Vanderson
authors.initials: V
authors.lastname: Rocha
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Department of Hematology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Szwajcer
authors.affiliation: Department of Hematology, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Valcarcel
authors.affiliation: Department of Medicine, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: meapen@mcw.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34
keywords: Cellular content; Hematological malignancy; Peripheral blood graft