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A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia

Laurene Fenwarth 1, 2 Xavier Thomas 3 Stephane Botton 4, 5 Nicolas Duployez 1 Jean-Henri Bourhis 5 Auriane Lesieur 1 Gael Fortin 6 Paul-Arthur Meslin 6 Ibrahim Yakoub-Agha 7, 8 Pierre Sujobert 9 Pierre-Yves Dumas 10, 11 Christian Recher 12 Delphine Lebon 13, 14 Celine Berthon 2 Mauricette Michallet 15 Arnaud Pigneux 16 Stephanie Nguyen 17 Sylvain Chantepie 18 Norbert Vey 19 Emmanuel Raffoux 20 Karine Celli-Lebras 21 Claude Gardin 22 Juliette Lambert 23, 24 Jean-Valere Malfuson 25 Denis Caillot 26 Sebastien Maury 27 Benoit Ducourneau 1 Pascal Turlure 28 Emilie Lemasle 29 Cecile Pautas 30 Sylvie Chevret 31 Christine Terre 23 Nicolas Boissel 20 Gerard Socie 20 Herve Dombret 20 Claude Preudhomme 1 Raphael Itzykson 6
Abstract : A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from the ALFA-0702 trial (NCT00932412). KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0). Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P = .01 and P = .02, respectively). Using KB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar time-dependent analysis, a significant interaction between KB score and HSCT, with HSCT in CR1 being detrimental only in patients with a good prognosis based on KB simulations (KB score >= 40; interaction test, P = .01). We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03606390
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Soumis le : vendredi 11 mars 2022 - 17:44:08
Dernière modification le : jeudi 19 mai 2022 - 17:13:30

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Laurene Fenwarth, Xavier Thomas, Stephane Botton, Nicolas Duployez, Jean-Henri Bourhis, et al.. A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia. BLOOD, 2021, 137 (4), pp.524-532. ⟨10.1182/blood.2020005524⟩. ⟨hal-03606390⟩

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