The watch-and-wait approach for patients with juvenile myelomonocytic leukemia: results of the French cohort

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.

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Journal
Blood
Published
2025-09-19
DOI
https://doi.org/10.1182/blood.2025029916
Citations
2
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
3.54
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article

The watch-and-wait approach for patients with juvenile myelomonocytic leukemia: results of the French cohort

Audrey Grain, Bénédicte Neven, Élodie Lainey, Hélène Cavé et al.
2 citations
Blood
Acute Myeloid Leukemia Research
3.54
article

The watch-and-wait approach for patients with juvenile myelomonocytic leukemia: results of the French cohort

Audrey Grain, Bénédicte Neven, Élodie Lainey, Hélène Cavé, André Baruchel, Jean‐Hugues Dalle, Pauline Durand-Smet, Marion Strullu, Marie-Émilie Dourthe, Chloé Arfeuille, Mathieu Simonin, Quentin Neven, Arnaud Petit, Brigitte Nelken, C. El Khouri, Arthur Sterin, Marie Nolla, Odile Fenneteau, Aurélie Caye‐Eude, Frédéric Millot, Sylvie Chevret, Mony Fahd
article en
2 citations

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.

BloodVol. 147(4)
Délégation Paris 5 (FR), Hôpital Necker-Enfants Malades (FR), Inserm (FR), Institut Universitaire de France (FR), Université Paris Cité (FR), Université de Lille (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire de Toulouse (FR), Université de Poitiers (FR), Sorbonne Université (FR), Institut Necker Enfants Malades (FR), Hôpital Armand-Trousseau (FR), Assistance Publique Hôpitaux de Marseille (FR), Sorbonne Paris Cité (FR), Assistance Publique – Hôpitaux de Paris (FR), Clinical Investigation Center Plurithematic Tours (FR), Centre Hospitalier Universitaire de Poitiers (FR), Hôpital Robert-Debré (FR), Hôpital Saint-Louis (FR), Hôpital de la Timone (FR), Nantes Université (FR)
Openalex Percentile: Top 6%
Acute Myeloid Leukemia Research
3.54
DOISourceOpenAlex
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