Abstract
BackgroundThe impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored.MethodsWe retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.ResultsPatients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p = 4 × 10−5). Recipient age above 50 years was the only other factor associated with worse survivals.ConclusionsThese results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk.
Highlights
The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored
Rubio et al Journal of Hematology & Oncology (2017) 10:31 (Continued from previous page). These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic graft-versus-host disease (GVHD) without increased relapse risk
Prospective randomized studies have shown that in vivo T cell depletion with anti-thymocyte globulin (ATG) reduces the incidence of chronic graft-versus-host disease (cGVHD) without increasing the risk of relapse in allo-SCT performed with peripheral blood stem cells (PBSC) from matched related (MRD) or Matched unrelated donor (MUD) after conventional cyclophosphamide-based myeloablative conditioning (MAC) regimens for acute myeloid leukemia (AML) [14,15,16]
Summary
The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. Prospective randomized studies have shown that in vivo T cell depletion with anti-thymocyte globulin (ATG) reduces the incidence of cGVHD without increasing the risk of relapse in allo-SCT performed with PBSC from MRD or MUD after conventional cyclophosphamide-based MAC regimens for AML [14,15,16]. These results raise the question of the impact of use of ATG in the Flu-ivBu4 RTC, in which the balance between the GVH and GVL effects of allo-SCT might be more sensitive to T cell depletion. In this homogeneous cohort of patients, we compared post-transplant outcomes of 145 of those who received ATG for GVHD prophylaxis to the 421 patients who did not
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