title: Ex Vivo CD34+-Selected T Cell-Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response.
abstract: Ex vivo CD34+-selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+-selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34+-selected TCD allograft as a calcineurin inhibitor-free intervention for the prevention of GVHD in patients with acute leukemia and MDS.
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Hematology Department, Hospital Universitario Vall d'Herbon-Universidad Autonoma de Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Barba
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hilden
authors.affiliation: Department of Epidemiology and 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 Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Molly
authors.initials: M
authors.lastname: Maloy
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Djamilia
authors.initials: D
authors.lastname: Dierov
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Nieves
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Garrett
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Julie
authors.initials: J
authors.lastname: Sogani
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Christina
authors.initials: C
authors.lastname: Cho
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Barker
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Hugo
authors.initials: H
authors.lastname: Castro-Malaspina
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Ann A
authors.initials: AA
authors.lastname: Jakubowski
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Guenther
authors.initials: G
authors.lastname: Koehne
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Esperanza B
authors.initials: EB
authors.lastname: Papadopoulos
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Prockop
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Craig
authors.initials: C
authors.lastname: Sauter
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Roni
authors.initials: R
authors.lastname: Tamari
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
authors.affiliation: Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Avecilla
authors.affiliation: Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Meagher
authors.affiliation: 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 Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Jenna D
authors.initials: JD
authors.lastname: Goldberg
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Adult Bone Marrow Transplant Service, Division of Hematology/Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. Electronic address: ponced@mskcc.org.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Ponce
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000628:therapy*; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: Acute graft-versus-host disease; Chronic graft-versus-host disease; T cell–depleted transplantation