The watch-and-wait approach for patients with juvenile myelomonocytic leukemia: results of the French cohort
Abstract
Abstract Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive pediatric myeloproliferative neoplasm for which hematopoietic stem cell transplantation (HSCT) is currently the only established curative therapy. However, a watch-and-wait (W&W) approach has shown promise for long-term survival in selected cases. In this real-world study, we analyzed outcomes of patients with JMML initially managed with a W&W strategy within a nationwide cohort of 161 genetically characterized cases. W&W was chosen for 35 patients, with increasing adoption over time, reaching 39% in the 2016-to-2021 period. Most patients carried mutations in CBL (43%), NRAS (34%), or homozygous germ line SH2B3 (14%). Over a median follow-up of 6.5 years, 30 of 35 (86%) achieved long-term survival with partial or complete resolution of myeloproliferative symptoms, although clonal hematopoiesis persisted in nearly all survivors (18/20). Disease progression occurred in 5 patients (CBL, n = 3; NRAS, n = 1; PTPN11, n = 1), mostly within 2 years after diagnosis. Overall, in the W&W cohort, the 5-year overall and event-free survivals were 93.1% and 84.5%, respectively. In NRAS-mutated cases, age of <30 months, normal to slightly elevated fetal hemoglobin, platelet counts of >45 × 109/L, the absence of additional somatic mutations, and low DNA methylation profile were associated with favorable outcomes. In CBL-driven JMML, no predictive factor of adverse evolution was identified. Notably, W&W was effective in all patients with homozygous germ line SH2B3. These findings support W&W as a viable alternative in up to 30% of patients with JMML, potentially sparing them from HSCT-associated risks. Given the persistence of clonal hematopoiesis and the risk of extrahematological complications, long-term monitoring remains essential.
Article Details
Authors (22)
Quentin Neven
1Service d’Hémato-Immunologie Pédiatrique, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France
Chloé Arfeuille
2Service de Génétique Moléculaire, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France
Aurélie Caye-Eude
2Service de Génétique Moléculaire, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France
Pauline Durand
1Service d’Hémato-Immunologie Pédiatrique, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France
Elodie Lainey
15Hematology Laboratory, Robert Debré Hospital-Assistance Publique-Hôpitaux de Paris, INSERM UMR 1131-Hematology University Institute-Denis Diderot School of Medicine, Paris, France
Odile Fenneteau
4Service d’Hématologie Biologique, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France
Brigitte Nelken
5Service d'Hématologie Pédiatrique, Centre Hospitalier Universitaire de Lille, Lille, France
Marie Nolla
6Service d’Hématologie et Oncologie Pédiatrique, Centre Hospitalier Universitaire Toulouse, Toulouse, France
Arthur Sterin
7Service d’Hématologie et Oncologie Pédiatrique, Hôpital de la Timone, Marseille, France
Audrey Grain
8Service d’Hématologie-Oncologie-Immunologie Pédiatrique, CHU Nantes, Nantes, France
Céline Khouri
9Service d’Hématologie et Oncologie Pédiatrique, Hôpital Armand Trousseau, Université Paris Sorbonne, Paris, France
Mathieu Simonin
Marie-Emilie Dourthe
1Institut Necker Enfants Malades, INSERM U1151, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8253, Université Paris Cité, Paris, France
Mony Fahd
1Service d’Hémato-Immunologie Pédiatrique, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France
Frédéric Millot
10Service d’Hématologie et Oncologie Pédiatrique, Centre Hospitalier Universitaire Poitiers, Poitiers, France
Bénédicte Neven
Arnaud Petit
20Department of Pediatric Hematology and Oncology, Armand-Trousseau Hospital Assistance Publique–Hôpitaux de Paris and Sorbonne University, Paris, France
Sylvie Chevret
Jean-Hugues Dalle
27Hemato-Immunology Department, Robert Debré Academic Hospital, GHU AP-HP Nord Université Paris Cité, Paris, France
Andre Baruchel
Hélène Cavé
2Service de Génétique Moléculaire, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France
Marion Strullu
1Service d’Hémato-Immunologie Pédiatrique, Hôpital Robert Debré, Groupes Hospitalo-Universitaires Assistance Publique–Hôpitaux de Paris Nord, Université Paris Cité, Paris, France