title: T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease.
abstract: Thirty-one consecutive patients with acute myelogenous leukemia (AML) in first complete remission and 8 with AML in second complete remission received T cell-depleted allogeneic bone marrow transplants from HLA-identical sibling donors. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide. Those patients at risk for immune-mediated graft rejection received additional immune suppression with antithymocyte globulin and methylprednisolone in the early peritransplant period. Patients with AML who underwent allogeneic T-cell-depleted bone marrow transplantations (BMT) in first or second remission have achieved respective disease-free survival (DFS) probabilities of 77% (median follow-up at approximately 56 months) and 50% (median follow-up at approximately 48 months). Ten of 31 patients transplanted in first remission were > or = 40 years old and have attained a DFS at 4 years of 70%. For patients with AML transplanted in first or second remission, the respective cause-specific probabilities of relapse were 3.2% or 12.5%, and those of nonleukemic mortality were 19.4% or 37.5%. There were no cases of immune-mediated graft rejection and no cases of grade II to IV acute graft-versus-host disease (GVHD). All survivors enjoy Karnofsky performance scores (KPS) of 100%, except 2 patients with KPS of 80% to 90%. T-cell-depleted allogeneic BMT can provide durable DFS together with an excellent performance status in the majority of patients with de novo AML. In addition, GVHD is not an obligatory correlate of the graft-versus-leukemia benefit or freedom from relapse afforded by allogeneic BMT administered as postremission therapy for AML. This study provides a basis for prospective comparison with other postremission therapies considered standard in the management of patients with this disease.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Papadopoulos
authors.forename: M H
authors.initials: MH
authors.lastname: Carabasi
authors.forename: H
authors.initials: H
authors.lastname: Castro-Malaspina
authors.forename: B H
authors.initials: BH
authors.lastname: Childs
authors.forename: S
authors.initials: S
authors.lastname: Mackinnon
authors.forename: F
authors.initials: F
authors.lastname: Boulad
authors.forename: A P
authors.initials: AP
authors.lastname: Gillio
authors.forename: N A
authors.initials: NA
authors.lastname: Kernan
authors.forename: T N
authors.initials: TN
authors.lastname: Small
authors.forename: P
authors.initials: P
authors.lastname: Szabolcs
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Yahalom
authors.forename: N H
authors.initials: NH
authors.lastname: Collins
authors.forename: S A
authors.initials: SA
authors.lastname: Bleau
authors.forename: P M
authors.initials: PM
authors.lastname: Black
authors.forename: G
authors.initials: G
authors.lastname: Heller
authors.forename: R J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: J W
authors.initials: JW
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D006086:Graft vs Host Disease; D004854:Herpesvirus 4, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008212:Lymphocyte Depletion; D008232:Lymphoproliferative Disorders / Q000821:virology; D012074:Remission Induction; D013601:T-Lymphocytes; D013852:Thiotepa / Q000627:therapeutic use; D018183:Transplantation Chimera; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D013852:Thiotepa