Decitabine-based treatment strategy improved the outcome of HSCT in JMML: a retrospective cohort study

Front Immunol. 2024 Aug 26:15:1426640. doi: 10.3389/fimmu.2024.1426640. eCollection 2024.

Abstract

Introduction: Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients.

Methods: This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival.

Results: There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002).

Conclusion: Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments.

Keywords: FLAG protocol; decitabine; hematopoietic stem cell transplantation (HSCT); hypomethylating agents; juvenile myelomonocytic leukemia (JMML); maintenance treatment; pretransplant therapy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Cytarabine / administration & dosage
  • Cytarabine / therapeutic use
  • Decitabine* / administration & dosage
  • Decitabine* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Infant
  • Leukemia, Myelomonocytic, Juvenile* / mortality
  • Leukemia, Myelomonocytic, Juvenile* / therapy
  • Male
  • Retrospective Studies
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use

Substances

  • Decitabine
  • Vidarabine
  • fludarabine
  • Cytarabine

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (NSFC, Grant No. 82372312) and Clinical Research of Nanfang Hospital (Nanfang Hospital, Grant No. CR2021005).