Improved outcome in children compared to adolescents and young adults after allogeneic hematopoietic stem cell transplant for acute myeloid leukemia: a retrospective study from the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC)

Cécile Pochon (1) , Marie Detrait (2, 3) , Jean-Hugues Dalle (4) , Gérard Michel (5) , Nathalie Dhédin (6, 7) , Yves Chalandon (8) , Eolia Brissot (9, 10) , Edouard Forcade (11) , Anne Sirvent (12) , Faezeh Izzadifar-Legrand (13) , Mauricette Michallet (14) , Cécile Renard (15) , Ibrahim Yakoub-Agha (16, 17) , Fanny Gonzales (16) , Jacques-Olivier Bay (18) , Justyna Kanold (19) , Jérome Cornillon (20) , Claude Eric Bulabois (21) , Marie Angoso (11) , Stéphanie Nguyen (22) , Marie Balza (15) , Patrice Chevallier (23) , Fanny Rialland (23) , Ali Bazarbachi (24) , Yves Beguin (25) , Anne Huynh (26) , Anne-Lise Ménard (27) , Pascale Schneider (28) , Bénédicte Neven (29) , Catherine Paillard (30) , Nicole Raus (31) , Eliane Albuisson (32) , Thomas Remen (32) , Marie-Thérèse Rubio (2, 3)

1 Service d'Oncologie Pédiatrique [CHRU Nancy]
2 IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire
3 Service d'Hématologie [CHRU Nancy]
4 Service d'Hématologie Biologique [Hôpital Robert Debré, Paris]
5 TIMONE - Hôpital de la Timone [CHU - APHM]
6 AP-HP - Hopital Saint-Louis [AP-HP]
7 URP_3518 - Recherche clinique appliquée à l'hématologie
8 HUG - Hôpitaux Universitaires de Genève
9 CHU Saint-Antoine [AP-HP]
10 CRSA - Centre de Recherche Saint-Antoine
11 CHU Bordeaux
12 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
13 IPC - Institut Paoli-Calmettes
14 Centre Léon Bérard [Lyon]
15 HCL - Hospices Civils de Lyon
16 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
17 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
18 CHU Clermont-Ferrand
19 CHU Estaing [Clermont-Ferrand]
20 Institut de Cancérologie Lucien Neuwirth
21 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
22 CIMI - Centre d'Immunologie et des Maladies Infectieuses
23 CHU Nantes - Centre Hospitalier Universitaire de Nantes
24 AUB - American University of Beirut [Beyrouth]
25 CHU-Liège - Centre Hospitalier Universitaire de Liège
26 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
27 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
28 Hôpital Charles Nicolle [Rouen]
29 Hôpital Necker - Enfants Malades [AP-HP]
30 Hôpital de Hautepierre [Strasbourg]
31 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
32 DRCI - Délégation à la Recherche Clinique et à l'Innovation [CHRU Nancy]

Background There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, adolescents and young adults after a first allogeneic HSCT for AML. Methods In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (< 15 years, n = 564), adolescent and post-adolescent (APA) patients (15–25 years, n = 647) and young adults (26–40 years; n = 1434). Results With a median follow-up of 4.37 years (min–max 0.18–14.73 years), the probability of 2-year overall survival (OS) was 71.4% in children, 61.1% in APA patients and 62.9% in young adults ( p = 0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for APA patients and 29.4% for young adults— p = 0.0254, and 7.0% for children, 10.6% for APA patients and 14.2% for young adults, p < 0.0001; respectively). Whilst there was no difference between the three groups for grade I to IV acute GVHD CI at 3 months, the chronic GVHD CI at 2 years was higher in APA patients and young adults (31.4% and 36.4%, respectively) in comparison to the children (17.5%) ( p < 0.0001). In multivariable analysis, factors associated with death were AML cytogenetics (HR1.73 [1.29–2.32] for intermediate risk 1, HR 1.50 [1.13–2.01] for intermediate risk 2, HR 2.22 [1.70–2.89] for high cytogenetics risk compared to low risk), use of TBI ≥ 8 Grays (HR 1.33 [1.09–1.61]), disease status at transplant (HR 1.40 [1.10–1.78] for second Complete Remission (CR), HR 2.26 [1.02–4.98] for third CR and HR 3.07 [2.44–3.85] for active disease, compared to first CR), graft source (HR 1.26 [1.05–1.50] for Peripheral Blood Stem Cells compared to Bone Marrow) and donor age (HR 1.01 (1–1.02] by increase of 1 year). Conclusion Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that APA patients with AML could be beneficially treated with a chemotherapy-based MAC regimen and bone marrow as a stem cells source.

Domaines: Cancer

Cécile Pochon, Marie Detrait, Jean-Hugues Dalle, Gérard Michel, Nathalie Dhédin, et al.. Improved outcome in children compared to adolescents and young adults after allogeneic hematopoietic stem cell transplant for acute myeloid leukemia: a retrospective study from the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC). Journal of Cancer Research and Clinical Oncology, 2021, ⟨10.1007/s00432-021-03761-w⟩. ⟨hal-03355243⟩