title: Donor T-lymphocyte infusion for unrelated allogeneic bone marrow transplantation with CD3+ T-cell-depleted graft.
abstract: In T-cell-depleted allogeneic bone marrow transplantation (TCD-BMT) using unrelated donors, the role of donor lymphocyte infusion (DLI) for survival and disease control has not been defined. In a study of 116 patients (92 matched, 24 mismatched) who received CD3+ T-cell-depleted marrow graft, sequential infusions of escalated doses of donor T lymphocytes up to 1 x 10(6) CD3+ cells/kg were prospectively investigated. T cells were administered while patients were on cyclosporine, provided >or=grade II acute graft-versus-host-disease (GVHD) had not occurred. Acute GVHD of >or=grade II occurred in 27 of 110 (25%) patients before DLI and in 39 of 79 (49%) patients after DLI. In total, 12 of 27 (44%) patients without DLI and 44 of 72 (61%) patients who received DLI developed chronic GVHD. A total of 19 patients died of GVHD, with 17 of acute and two of chronic GVHD. Overall survival (OS) and event-free survival (EFS) at 5 years were 27 and 21%, respectively. The 2-year incidence of relapse was 14%. In multivariate analysis, only chronic GVHD was a good prognostic factor for both OS: hazard ratio (HR) 1.4, P=0.04, and EFS: HR 1.6, P=0.01. Both acute and chronic GVHD were favorable prognostic factors for relapse probability: HR 1.9 for both, P=0.02, 0.01, respectively. The 1-year cumulative incidence of transplant-related mortality (TRM), excluding cases of GVHD, was 42%. The two most common causes of 1-year non-GVHD death were viral infection (9%) and idiopathic pneumonia syndrome (12%). Although the incidence of relapse was low, the study suggests that the current scheme of DLI in unrelated TCD-BMT would not improve survival unless TRM decreases significantly.
authors.affiliation: Department of Internal Medicine, College of Medicine, The University of Iowa, IA, USA.
authors.forename: C-K
authors.initials: CK
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: deMagalhaes-Silverman
authors.forename: R J
authors.initials: RJ
authors.lastname: Hohl
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: J
authors.initials: J
authors.lastname: Buatti
authors.forename: B-C
authors.initials: BC
authors.lastname: Wen
authors.forename: A
authors.initials: A
authors.lastname: Schlueter
authors.forename: R G
authors.initials: RG
authors.lastname: Strauss
authors.forename: R D
authors.initials: RD
authors.lastname: Gingrich
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D016026:Bone Marrow Transplantation / Q000379:methods*; D017252:CD3 Complex / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011336:Probability; D012189:Retrospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000637:transplantation*; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D014916:Whole-Body Irradiation
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D003561:Cytarabine; D003520:Cyclophosphamide