title: CD8+ T-cell-depleted, matched unrelated donor, allogeneic bone marrow transplantation for advanced AML using busulfan-based preparative regimens.
abstract: The role of T-cell depletion (TCD) to prevent graft-versus-host disease (GVHD) after matched unrelated donor allogeneic bone marrow transplant (MUD BMT) remains undefined. Most studies employ total body irradiation and pan TCD. Between March 1993 and June 2002, we treated 33 relapsed acute myelogenous leukemia (AML) patients with busulfan-based preparative regimens and selective TCD. The preparative regimen consisted of busulfan 14 mg/kg, cyclophosphamide 120 mg/kg and VP-16 50 mg/kg in all but one patient who only received busulfan and cyclophosphamide. Donor marrow was depleted of CD8+ T cells by immunomagnetic bead separation. The patients were also treated with cyclosporine and methylprednisolone or FK-506 and mini-dose methotrexate. Four (15%) of 33 patients developed graft failure or rejection. However, three of these patients were serologically mismatched at HLA-Cw. Although 67% of evaluable patients developed acute GVHD, severe grade III-IV acute GVHD only developed in 19%. The severity of acute GVHD correlated with the degree of CD8+ TCD. Median relapse-free survival was 5 months among 20 patients treated with active AML, and 28 months among 13 patients treated in complete remission. Our results confirm that MUD BMT with CD8+ TCD for AML is a potentially curative treatment option.
authors.affiliation: Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. kalaycm@ccf.org
authors.forename: M
authors.initials: M
authors.lastname: Kalaycio
authors.forename: L
authors.initials: L
authors.lastname: Rybicki
authors.forename: B
authors.initials: B
authors.lastname: Pohlman
authors.forename: R
authors.initials: R
authors.lastname: Sobecks
authors.forename: E
authors.initials: E
authors.lastname: Ball
authors.forename: D
authors.initials: D
authors.lastname: Cook
authors.forename: S
authors.initials: S
authors.lastname: Andresen
authors.forename: E
authors.initials: E
authors.lastname: Kuczkowski
authors.forename: B
authors.initials: B
authors.lastname: Bolwell
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D002066:Busulfan / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes; D002330:Carmustine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan; D002330:Carmustine