title: T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect.
abstract: Thirty-eight patients with hematological malignancies, received T cell-depleted marrow transplants (BMT) and cyclosporine to prevent acute graft-versus-host disease (aGVHD), followed by delayed add-back of donor lymphocytes to prevent leukemia relapse. In 26 patients scheduled for donor T cell add-back of 2 x 10(6) cells/kg on day 30 and 5 x 10(7) cells/kg on day 45 (schedule 1), the overall probability of grade > or = II aGVHD developing was 31.5%, with a 15.5% probability of aGVHD occurring after T cell add-back. In 12 patients receiving 10(7) donor T cells/kg on day 30 (schedule 2), the probability of grade > or = II aGVHD was 100%. The incidence of grade III-IV aGVHD was higher in schedule 2 than in schedule 1 (P=0.02). Of 24 evaluable patients, 10 (46%) developed chronic GVHD which was limited in eight and extensive in two. Current disease-free survival for 18 patients at standard risk for relapse (chronic myeloid leukemia (CML) in chronic or accelerated phase, acute myeloid leukemia in remission) vs 20 patients with more advanced leukemia or multiple myeloma were respectively 72% vs 12% (P < 0.01) with a 29% vs 69% probability of relapse (P=0.08). In 12 CML patients surviving more than 3 months, PCR analysis of the BCR/ABL transcript showed that minimal residual disease after T cell add-back was transient except in two patients who developed hematological relapse. Results indicate that the risk of acute GVHD is low following substantial T cell doses, transfused 45 days after transplant, using cyclosporine prophylaxis. Furthermore a graft-versus-leukemia effect was conserved.
authors.affiliation: Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: J
authors.initials: J
authors.lastname: Tisdale
authors.forename: J
authors.initials: J
authors.lastname: Molldrem
authors.forename: E
authors.initials: E
authors.lastname: Clave
authors.forename: C
authors.initials: C
authors.lastname: Dunbar
authors.forename: M
authors.initials: M
authors.lastname: Cottler-Fox
authors.forename: S
authors.initials: S
authors.lastname: Phang
authors.forename: C
authors.initials: C
authors.lastname: Carter
authors.forename: P
authors.initials: P
authors.lastname: Okunnieff
authors.forename: N S
authors.initials: NS
authors.lastname: Young
authors.forename: E J
authors.initials: EJ
authors.lastname: Read
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods; D003520:Cyclophosphamide / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000150:complications; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D006087:Graft vs Host Reaction; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007938:Leukemia / Q000150:complications / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D013601:T-Lymphocytes / Q000637:transplantation; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide