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. 2018 Feb;103(2):256-265.
doi: 10.3324/haematol.2017.178251. Epub 2017 Dec 14.

Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Xavier Poiré  1 , Myriam Labopin  2   3 , Emmanuelle Polge  2   3 , Jakob Passweg  4 , Charles Craddock  5 , Didier Blaise  6 , Jan J Cornelissen  7 , Liisa Volin  8 , Nigel H Russell  9 , Gérard Socié  10 , Mauricette Michallet  11 , Nathalie Fegueux  12 , Patrice Chevallier  13 , Arne Brecht  14 , Mathilde Hunault-Berger  15 , Mohamad Mohty  2   3 , Jordi Esteve  16 , Arnon Nagler  2   17
Affiliations

Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Xavier Poiré et al. Haematologica. 2018 Feb.

Abstract

Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 (FLT3-ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3-ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively (P<0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft-versus-host disease and relapse-free survival, and overall survival. In this elderly population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients ≥ 60 with FLT3-ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients.

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Figures

Figure 1.
Figure 1.
Cumulative incidence of chronic graft-versus-host disease (GvHD). The 2-year cumulative incidence of chronic GvHD was 34% (95% CI: 28.4–40.5) in the entire cohort (N=291).
Figure 2.
Figure 2.
Non-relapse mortality (NRM), relapse incidence (RI), overall survival (OS) and leukemia-free survival (LFS) per disease status (first complete remission (CR1), second remission (CR2) and active disease (Active D)). (A) The 2-year cumulative incidence of NRM was 18% (95% CI: 12.8–23.9) in CR1 patients, 21.6% (95% CI: 8.9–37.9) in CR2 patients and 28.6% (95% CI: 15.6–43) in Active D patients. (B) The 2-year cumulative incidence of relapse was 26.1% (95% CI: 19.9–32.6) in CR1 patients, 56.8% (95% CI: 37.1–72.3) in CR2 patients and 61.9% (95% CI: 44.9–75) in Active D patients. (C) The 2-year probability of OS was 58.7% (95% CI: 51.2–66.1) in CR1 patients, 28.8% (95% CI: 12.3–45.4) and 9.5% (95% CI: 0.6–18.4) in Active D patients. (D) The 2-year probability of LFS was 55.9% (95% CI: 48.6–63.3) in CR1 patients, 21.6% (95% CI: 6.4–36.8) and 9.5% (95% CI: 0.6–18.4).
Figure 3.
Figure 3.
Graft-versus-host disease and relapse-free survival (GRFS) per disease status (first complete remission (CR1), second remission (CR2) and active disease (Active D)). The 2-year probability of GRFS was 41.7% (95% CI: 34.3–49.2) in CR1 patients, 18.1% (95% CI: 3.6–32.6) in CR2 patients and 2.4% (95% CI: 0–7.2) in Active D patients.
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