TcRαβ-depleted haploidentical transplantation results in adult acute leukemia patients

Abstract

Introduction: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. Patient and method: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia. 84.4% of patients were in the high-risk group, and 55.9% were not in remission. The preparative regimen included thiotepa, melphalan, fludarabine, and anti-thymocyte globulin-Fresenius. Grafts were peripheral blood stem cells engineered by TcR-alpha/beta depletion. Results: Neutrophil and platelet engraftment was achieved on days +12 (range, 10.5–15) and +11 (range, 10–12). All but three patients were engrafted with full donor chimerism. Grade III-IV acute GVHD occurred in two (5.9%) patients and chronic GVHD in two (6.1%). Disease-free survival and overall survival were 42 and 54% at 1 year, respectively. AML as disease type (HR: 4.87, 95% CI: 1.50–15.87) and mother as donor (HR: 1.05, 95% CI: 1.00–1.11) were found to be independent risk factors on patient survival. Mortality and NRM in the first 100 days were 5 of 34 (14.7%) and 4 of 34 (11.7%). Relapse was the main cause of death (56.3%). T-cell reconstitution appears to be faster than that reported in published data with CD3/CD19-depleted grafts. Conclusion: αβ T-cell-depleted haploidentical transplantation may be a good alternative for high-risk patients if there are no human leukocyte antigen matched donors.