Allogeneic Hematopoietic Cell Transplantation for Juvenile Myelomonocytic Leukemia with a Busulfan, Fludarabine, and Melphalan Regimen: JPLSG JMML-11

• Published in: Transplantation and cellular therapy 2024-01, Vol.30 (1), p.105.e1-105.e10
• Main Authors: Sakashita, Kazuo, Yoshida, Nao, Muramatsu, Hideki, Ohtsuka, Yoshitoshi, Watanabe, Kenichiro, Yabe, Miharu, Kakuda, Harumi, Honda, Yuko, Watanabe, Tomoyuki, Haba, Masami, Ohmori, Shigeru, Matsuda, Kazuyuki, Yuza, Yuki, Saito, Akiko, Horibe, Keizo, Adachi, Souichi, Manabe, Atsushi
• Format: Article
• Language: English
• Subjects: Busulfan; Busulfan - therapeutic use; Child; Fludarabine; Hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Infant, Newborn; Japan; Juvenile myelomonocytic leukemia; Leukemia, Myelomonocytic, Juvenile - complications; Leukemia, Myelomonocytic, Juvenile - drug therapy; Lymphoma - complications; Lymphoma - drug therapy; Melphalan; Melphalan - therapeutic use; Prospective Studies; Retrospective Studies; Transplantation, Homologous
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.10.002

•JMML-11 provides evidence of the effectiveness of a BU+FLU+MEL regimen for treating JMML.•Notable results include a 3-year OS of 63% and EFS of 52% in patients with JMML.•A higher disease burden before conditioning was a negative prognostic indicator.•HLA-matched unrelated bone marrow donors were associated with improved outcomes. Juvenile myelomonocytic leukemia (JMML), which is classified as a myelodysplastic/myeloproliferative neoplasm, is a rare hematologic malignancy of childhood. Most patients with JMML require allogeneic hematopoietic cell transplantation (HCT) as a curative therapy. A Japanese retrospective analysis demonstrated favorable outcomes for a busulfan (BU) + fludarabine (FLU) + melphalan (MEL) regimen, with an overall survival (OS) of 72% and an event-free survival (EFS) of 53%. To further validate the efficacy and safety of this regimen, the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) conducted a nationwide prospective study, JMML-11. Between July 2011 and June 2017, 28 patients with newly diagnosed JMML were enrolled in JMML11. Low-dose chemotherapy for tumor control before HCT was recommended, and patients treated with AML-type chemotherapy and azacitidine were excluded. The conditioning regimen comprised i.v. BU, 16 doses administered every 6 h, with dose adjustment based on pharmacokinetic (PK) studies on days -11 to -8; FLU, 30 mg/m2/day or 1 mg/kg/day for patients