A predictive classifier of poor prognosis in transplanted patients with juvenile myelomonocytic leukemia: a study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire
Déborah Meyran,
Chloé Arfeuille,
Sylvie Chevret,
Quentin Neven,
Aurélie Caye-Eude,
Elodie Lainey,
Arnaud Petit,
Fanny Rialland,
Gérard Michel,
Dominique Plantaz,
Charlotte Jubert,
Alexandre Theron,
Virginie Gandemer,
Marie Ouachée-Chardin,
Catherine Paillard,
Bénédicte Bruno,
Nimrod Buchbinder,
Cécile Pochon,
Charlotte Calvo,
Mony Fahd,
André Baruchel,
Hélène Cavé,
Jean-Hugues Dalle,
Marion Strullu
Affiliations
Déborah Meyran
Service d’Hémato-Immunologie pédiatrique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris, France; Children's Cancer Centre, Royal Children's Hospital, Parkville, Victoria, Australia; Sir Peter MacCallum Dept of Oncology, University of Melbourne, Melbourne, 3010 Australia
Chloé Arfeuille
Service de de Génétique Moléculaire, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris, France; INSERM UMR_S1131, Institut Universitaire d’Hématologie, Université Paris Cité, Paris-Cité, Paris
Sylvie Chevret
Service de biostatistique et information médicale, Hôpital Saint Louis, GHU AP-HP Nord – Université Paris Cité, Paris
Quentin Neven
Service d’Hémato-Immunologie pédiatrique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris
Aurélie Caye-Eude
Service de de Génétique Moléculaire, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris
Elodie Lainey
INSERM UMR_S1131, Institut Universitaire d’Hématologie, Université Paris Cité, Paris-Cité, Paris, France; Service d’Hématologie Biologique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris
Arnaud Petit
Service d’Hémato-Immunologie pédiatrique, Hôpital Armand Trousseau, Université Paris Sorbonne, Paris
Fanny Rialland
Service d’Onco-Hématologie pédiatrique, CHU de Nantes, Nantes
Gérard Michel
Service d’Hématologie pédiatrique, Assistance Publique des Hôpitaux de Marseille AP-HM, Marseille
Dominique Plantaz
Service d’Onco-Hématologie pédiatrique, CHU de Grenoble, Grenoble
Charlotte Jubert
CHU Bordeaux, Service d’hématologie oncologie pédiatrique, F-33000 Bordeaux
Alexandre Theron
Department of Pediatric Oncology and Hematology, CHU Montpellier, France; IRMB, University of Montpellier, INSERM, Montpellier
Virginie Gandemer
Service d’Onco-Hématologie pédiatrique, CHU de Rennes, Rennes
Marie Ouachée-Chardin
Service d’Onco-Hématologie pédiatrique, IHOPE, Lyon
Catherine Paillard
Service de Pédiatrie, Hôpital de Hautepierre, Strasbourg
Bénédicte Bruno
Service de Pédiatrie, Hôpital de Jeanne de Flandre, Lille
Nimrod Buchbinder
Service d’Onco-Hématologie pédiatrique, CHU de Rouen, Rouen
Cécile Pochon
Service d’Onco-Hématologie pédiatrique, Hôpital d’Enfants de Brabois, Vandoeuvre lès Nancy
Charlotte Calvo
Service d’Hémato-Immunologie pédiatrique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris
Mony Fahd
Service d’Hémato-Immunologie pédiatrique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris
André Baruchel
Service d’Hémato-Immunologie pédiatrique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris, France; Unité Inserm U976, Université Paris Cité, Paris-Cité, Paris
Hélène Cavé
Service de de Génétique Moléculaire, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris, France; INSERM UMR_S1131, Institut Universitaire d’Hématologie, Université Paris Cité, Paris-Cité, Paris
Jean-Hugues Dalle
Service d’Hémato-Immunologie pédiatrique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris, France; Unité Inserm U976, Université Paris Cité, Paris-Cité, Paris
Marion Strullu
Service d’Hémato-Immunologie pédiatrique, Hôpital Robert Debré, GHU AP-HP Nord – Université Paris Cité, Paris, France; INSERM UMR_S1131, Institut Universitaire d’Hématologie, Université Paris Cité, Paris-Cité, Paris
Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myeloproliferative neoplasm requiring hematopoietic stem cell transplantation (HSCT) in most cases. We retrospectively analyzed 119 JMML patients who underwent first allogeneic HSCT between 2002 and 2021. The majority (97%) carried a RAS-pathway mutation, and 62% exhibited karyotypic alterations or additional mutations in SETBP1, ASXL1, JAK3 and/or the RAS pathway. Relapse was the primary cause of death, with a 5-year cumulative incidence of 24.6% (95%CI: 17.1-32.9). Toxic deaths occurred in 12 patients, resulting in treatmentrelated mortality (TRM) of 9.0% (95%CI: 4.6-15.3). The 5-year overall (OS) and event-free survival were 73.6% (95%CI: 65.7-82.4) and 66.4% (95%CI: 58.2-75.8), respectively. Four independent adverse prognostic factors for OS were identified: age at diagnosis >2 years, time from diagnosis to HSCT >6 months, monocyte count at diagnosis >7.2x109/L, and the presence of additional genetic alterations. Based on these factors, we proposed a predictive classifier. Patients with three or more predictors (21% of the cohort) had a 5-year OS of 34.2%, whereas those with none (7%) had a 5-year OS of 100%. Our study demonstrates improved transplant outcomes compared to prior published data, which can be attributed to the synergistic impacts of a low TRM and a reduced yet still substantial relapse incidence. By integrating genetic information with clinical and hematological features, we have devised a predictive classifier. This classifier effectively identifies a subgroup of patients who are at a heightened risk of unfavorable post-transplant outcomes who would benefit novel therapeutic agents and post-transplant strategies.
