title: CD34-Selected Hematopoietic Stem Cell Transplants Conditioned with Myeloablative Regimens and Antithymocyte Globulin for Advanced Myelodysplastic Syndrome: Limited Graft-versus-Host Disease without Increased Relapse.
abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for patients with myelodysplastic syndrome (MDS). Donor T cells are critical for the graft-versus-tumor effect but carry the risk of graft-versus-host disease (GVHD). CD34 selection with immunomagnetic beads has been an effective method of depleting alloreactive donor T cells from the peripheral blood graft and has been shown to result in significant reduction in acute and chronic GVHD. We analyzed the outcomes of 102 adults (median age, 57.6 years) with advanced MDS who received a CD34-selected allo-HSCT between January 1997 and April 2012 at Memorial Sloan Kettering Cancer Center. The cumulative incidences of grades II to IV acute GVHD were 9.8% at day 100 (95% confidence interval [CI], 5.0% to 16.5%) and 15.7% at day 180 (95% CI, 9.4% to 23.4%). The cumulative incidence of chronic GVHD at 1 year was 3.9% (95% CI, 1.3% to 9.0%). The cumulative incidences of relapse were 11.8% at 1 year (95% CI, 6.4% to 18.9%) and 15.7% at 2 years (95% CI, 9.4% to 23.4%). Forty-eight patients were alive with a median follow-up of 71.7 months. Rates of overall survival (OS) were 56.9% at 2 years (95% CI, 48% to 67.3%) and 49.3% at 5 years (95% CI, 40.4% to 60.2%). Rates of relapse-free survival (RFS) were 52.0% at 2 years (95% CI, 41.9% to 61.1%) and 47.6% at 5 years (95% CI, 37.5% to 56.9%). The cumulative incidences of nonrelapse mortality were 7.8% at day 100 (95% CI, 3.7% to 14.1%), 22.5% at 1 year (95% CI, 15.0% to 31.1%), and 33.4% at 5 years (95% CI, 24.2% to 42.6%) post-transplant. The incidence of chronic GVHD/RFS overlapped with RFS. These findings demonstrate that ex vivo T cell-depleted allo-HSCT by CD34 selection offers long-term OS and RFS with low incidences of acute and chronic GVHD and without an increased risk of relapse.
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address: ronitamari@yahoo.com.
authors.forename: Roni
authors.initials: R
authors.lastname: Tamari
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Esperanza B
authors.initials: EB
authors.lastname: Papadopoulos
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Ann A
authors.initials: AA
authors.lastname: Jakubowski
authors.affiliation: Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hilden
authors.affiliation: Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Devlin
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Jenna D
authors.initials: JD
authors.lastname: Goldberg
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Ponce
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Sauter
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Maloy
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Dara Y
authors.initials: DY
authors.lastname: Herman
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Virginia
authors.initials: V
authors.lastname: Klimek
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York; Pediatric Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Giralt
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Hugo
authors.initials: H
authors.lastname: Castro-Malaspina
mesh_terms: D000208:Acute Disease; D000368:Aged; D018952:Antigens, CD34 / Q000737:chemistry / Q000276:immunology; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D018189:Immunomagnetic Separation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D060787:Neoplasm Grading; D011446:Prospective Studies; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists
keywords: Acute and chronic GVHD; Advanced myelodysplastic syndromes; CD34 selection; Relapse; Relapse/chronic GVHD-free survival