title: T cell-depleted unrelated donor stem cell transplantation provides favorable disease-free survival for adults with hematologic malignancies.
abstract: We report a prospective phase II clinical trial in 35 adult patients (median age 40.5 years) with hematologic malignancies who received T cell-depleted, hematopoietic stem cell transplants from HLA-compatible, unrelated donors. The cytoreductive regimen consisted of hyperfractionated total-body irradiation, thiotepa, and fludarabine. The preferred graft source was granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC). PBSC were CD34(+) selected, followed by sheep erythrocyte rosetting to deplete residual T cells. Anti-thymocyte globulin provided graft rejection prophylaxis. No additional graft-versus-host disease (GVHD) prophylaxis was planned. Estimated disease-free survival at 4 years is 56.8% for the entire group and 75% in patients with standard-risk disease. The cumulative incidence of relapse is 6%. Acute GVHD grade II-III developed in 9% and chronic GVHD in 29% of patients. Fatal infections occurred in 5 of 35 (14%) patients. There was 1 late graft failure. This study demonstrates durable engraftment with a low overall incidence of GVHD. Its curative potential is reflected in the remarkably low relapse rate at 4 years.
authors.affiliation: Adult Allogeneic Bone Marrow Transplant Service, Division of Hematologic-Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10065, USA. jakubowa@mskcc.org
authors.forename: Ann A
authors.initials: AA
authors.lastname: Jakubowski
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Small
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.forename: Hugo
authors.initials: H
authors.lastname: Castro-Malaspina
authors.forename: Nancy
authors.initials: N
authors.lastname: Collins
authors.forename: Guenther
authors.initials: G
authors.lastname: Koehne
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Hsu
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Perales
authors.forename: Genovefa
authors.initials: G
authors.lastname: Papanicolaou
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.forename: Esperanza B
authors.initials: EB
authors.lastname: Papadopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult