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

Laurene Fenwarth (1, 2) , Xavier Thomas (3) , Stephane De 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 (11) , Stephanie Nguyen (16) , Sylvain Chantepie (17) , Norbert Vey (18) , Emmanuel Raffoux (19) , Karine Celli-Lebras (20) , Claude Gardin (21) , Juliette Lambert (22, 23) , Jean-Valere Malfuson (24) , Denis Caillot (25) , Sebastien Maury (26) , Benoit Ducourneau (1) , Pascal Turlure (27) , Emilie Lemasle (28) , Cecile Pautas (29) , Sylvie Chevret (30) , Christine Terre (22) , Nicolas Boissel (19) , Gerard Socie (19) , Herve Dombret (19) , Claude Preudhomme (1) , Raphael Itzykson (6)

1 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
2 CHU Lille
3 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
4 IGR - Institut Gustave Roussy
5 Département d'hématologie [Gustave Roussy]
6 GenCellDi (U944 / UMR7212) - Génomes, biologie cellulaire et thérapeutiques
7 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
8 EBMT - Centre International des greffes [CHU Saint-Antoine]
9 Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
10 CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France.
11 Biothérapies des maladies génétiques et cancers
12 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
13 CHU Amiens-Picardie
14 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
15 Centre Léon Bérard [Lyon]
16 CIMI - Centre d'Immunologie et des Maladies Infectieuses
17 IHBN - Institut d'Hématologie de Basse-Normandie
18 Institut Paoli-Calmettes
19 AP-HP - Hopital Saint-Louis [AP-HP]
20 IUH - Institut Universitaire d'Hématologie
21 Hôpital Avicenne [AP-HP]
22 CHV - Centre Hospitalier de Versailles André Mignot
23 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
24 CTSA - Centre de Transfusion Sanguine des Armées
25 CHU Dijon
26 CHU Henri Mondor [Créteil]
27 Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges]
28 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
29 Service d'hématologie clinique
30 CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité

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.

Domaines: Sciences du Vivant [q-bio]

Laurene Fenwarth, Xavier Thomas, Stephane De 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⟩