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Multicenter Study
. 2017 Jan 24;10(1):31.
doi: 10.1186/s13045-016-0389-4.

Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party

Marie Thérèse Rubio  1   2   3 , Maud D'Aveni-Piney  4   5   6 , Myriam Labopin  7   8   9   10 , Rose-Marie Hamladji  11 , Miguel A Sanz  12 , Didier Blaise  13 , Hakan Ozdogu  14 , Etienne Daguindeau  15 , Carlos Richard  16 , Stella Santarone  17 , Giuseppe Irrera  18 , Ibrahim Yakoub-Agha  19 , Moshe Yeshurun  20 , Jose L Diez-Martin  21 , Mohamad Mohty  7   8   9   10 , Bipin N Savani  7   22 , Arnon Nagler  7   10   23
Affiliations
Multicenter Study

Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party

Marie Thérèse Rubio et al. J Hematol Oncol. .

Abstract

Background: 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.

Methods: We 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.

Results: Patients 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.

Conclusions: 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 GVHD without increased relapse risk.

Keywords: Acute myeloid leukemia; Allogeneic stem cell transplantation; GRFS; Graft-versus-host disease; HLA-matched related donor; In vivo T cell depletion; Relapse incidence.

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Figures

Fig. 1
Fig. 1
Cumulative incidence of chronic GVHD according to the use of ATG. a Overall incidence of chronic GVHD and b incidence of extensive chronic GVHD in the ATG and no-ATG groups as mentioned
Fig. 2
Fig. 2
Transplant outcomes according to the use of ATG. Cumulative incidence of non-relapse mortality (NRM) (a), of relapse (b), leukemia-free survival (c), and overall survival (d) in the ATG and no-ATG groups as mentioned
Fig. 3
Fig. 3
GRFS according to the use of ATG
See this image and copyright information in PMC

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