title: CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission.
abstract: The appropriate timing of bone marrow transplantation (BMT) for adults with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is controversial. Although allogeneic transplantation results in a lower risk of disease recurrence than intensive chemotherapy alone, overall outcome following BMT may not be improved due to the higher incidence of therapy-related fatal complications, frequently as a result of the development of graft-versus-host disease (GVHD). Selective T-cell depletion of donor marrow can reduce the incidence of GVHD and thereby limit transplant-related toxicity. Herein we report the risk of GVHD, incidence of transplant related mortality (TRM), likelihood of disease relapse, and overall survival in adult patients undergoing BMT with CD6 depleted allogeneic marrow for acute leukemia in first remission. Forty-one consecutive allogeneic transplants were performed on patients with acute leukemia and high-risk features (28 AML, 13 ALL) using T12 monoclonal antibody and complement to remove CD6+ T cells from donor marrow. No pre- or posttransplant immune suppressive medications for GVHD prophylaxis were administered. The actuarial estimated risk of grade 2 to 4 acute GVHD was 15% in patients receiving HLA identical grafts. Chronic GVHD developed in five patients. The estimated risk of TRM for patients in first complete remission was 5% at Day +100 and 16% at 2 years. Fatalities attributable to infection with cytomegalovirus or Epstein-Barr virus occurred in only three patients. Estimated probabilities of relapse, overall survival, and event-free survival at 4 years were 25%, 71%, and 63%, respectively. No significant differences in GVHD, TRM, relapse rate, or survival was observed for patients with AML compared with those with ALL. Allogeneic transplantation with CD6 depleted bone marrow is effective in consolidating remissions of high-risk patients with acute leukemia in first remission without excessive toxicity.
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: D
authors.initials: D
authors.lastname: Fairclough
authors.forename: M
authors.initials: M
authors.lastname: Robertson
authors.forename: E
authors.initials: E
authors.lastname: Alyea
authors.forename: K
authors.initials: K
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Freedman
authors.forename: L
authors.initials: L
authors.lastname: Bartlett-Pandite
authors.forename: D
authors.initials: D
authors.lastname: Fisher
authors.forename: R L
authors.initials: RL
authors.lastname: Schlossman
authors.forename: R
authors.initials: R
authors.lastname: Stone
authors.forename: C
authors.initials: C
authors.lastname: Murray
authors.forename: A
authors.initials: A
authors.lastname: Freeman
authors.forename: K
authors.initials: K
authors.lastname: Marcus
authors.forename: P
authors.initials: P
authors.lastname: Mauch
authors.forename: L
authors.initials: L
authors.lastname: Nadler
authors.forename: J
authors.initials: J
authors.lastname: Ritz
mesh_terms: D000208:Acute Disease; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology / Q000401:mortality; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007239:Infections / Q000209:etiology / Q000401:mortality; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D015993:Life Tables; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000628:therapy; D012074:Remission Induction; D012306:Risk; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D003561:Cytarabine