Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transpl

Publication Type
Journal Article
Year of Publication
2012
Authors
Pasquini, Marcelo C; Devine, Steven; Mendizabal, Adam; Baden, Lindsey R; Wingard, John R; Lazarus, Hillard M; Appelbaum, Frederick R; Keever-Taylor, Carolyn A; Horowitz, Mary M; Carter, Shelly; O'Reilly, Richard J; Soiffer, Robert J
Secondary
J Clin Oncol
Volume
30
Pagination
3194-201
Date Published
2012 Sep 10
Keywords
Antigens, CD34; Clinical Trials as Topic; Female; Graft Rejection; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Lymphocyte Depletion; Male; Siblings; T-Lymphocyte Subsets; Treatment Outcome
Abstract

PURPOSE: T-cell depletion (TCD) reduces the incidence of graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). However, concerns about relapse, graft rejection, and variability in technique have limited the widespread application of this approach.

PATIENTS AND METHODS: Outcomes of 44 patients receiving HLA-identical sibling TCD grafts using a uniform technique for CD34(+) selection as the sole form of immune suppression were compared with outcomes of 84 patients receiving T-replete grafts and pharmacologic immune suppression therapy (IST).

RESULTS: Groups were similar, except for fewer men (36% with TCD v 56% with IST) and more frequent use of radiation-containing regimens (100% with TCD v 50% with IST) in the CD34-selected TCD cohort. The proportion of patients with neutrophil engraftment at day 28 was similar (96% with IST and 100% with TCD grafts). The 100-day rates of grade 2 to 4 acute GVHD were 39% and 23% with IST and TCD grafts, respectively (P = .07). Corresponding 2-year rates of chronic GVHD were lower with TCD grafts than IST (19% v 50%, respectively; P < .001). There were no differences in rates of graft rejection, leukemia relapse, treatment-related mortality, and disease-free and overall survival rates. At 1 year, 54% and 12% of patients were still on immunosuppression in the IST and TCD cohorts, respectively. TCD was associated with a higher GVHD-free survival at 2 years compared with IST (41% v 19%, respectively; P = .006).

CONCLUSION: These results suggest that TCD via CD34 selection might lower long-term morbidity as a result of chronic GVHD without negatively impacting relapse rates in patients with acute myeloid leukemia. Additional prospective studies should be undertaken to definitively address the role of TCD in HCT.