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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 transplantation. J Clin Oncol 2012 Sep 10;30(26):3194-201

Date

08/08/2012

Pubmed ID

22869882

Pubmed Central ID

PMC3434978

DOI

10.1200/JCO.2012.41.7071

Scopus ID

2-s2.0-84866554399 (requires institutional sign-in at Scopus site)   131 Citations

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.

Author List

Pasquini MC, Devine S, Mendizabal A, Baden LR, Wingard JR, Lazarus HM, Appelbaum FR, Keever-Taylor CA, Horowitz MM, Carter S, O'Reilly RJ, Soiffer RJ

Authors

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

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