Azacitidine (Vidaza®) in Pediatric Patients with Relapsed Advanced MDS and JMML: Results of a Phase I/II Study by the ITCC Consortium and the EWOG-MDS Group (Study ITCC-015)

Alba Rubio-San-Simón, Natasha K A van Eijkelenburg, Raoull Hoogendijk, Henrik Hasle, Charlotte M Niemeyer, Michael N Dworzak, Marco Zecca, Marta Lopez-Yurda, Julie M Janssen, Alwin D R Huitema, Marry M van den Heuvel-Eibrink, Eric J Laille, Harm van Tinteren, Christian M Zwaan

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Advanced myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematological malignancies in children. A second allograft is recommended if a relapse occurs after hematopoietic stem cell transplantation, but the outcome is poor.

OBJECTIVE: We conducted a phase I/II multicenter study to evaluate the safety, pharmacokinetics, and activity of azacitidine in children with relapsed MDS/JMML prior to the second hematopoietic stem cell transplantation.

METHODS: Patients enrolled from June 2013 to March 2019 received azacitidine intravenously/subcutaneously once daily on days 1-7 of a 28-day cycle. The MDS and JMML cohorts followed a two-stage design separately, with a safety run-in for JMML. Response and safety data were used to evaluate efficacy and establish the recommended dose. Pharmacokinetics was also analyzed. The study closed prematurely because of low recruitment.

RESULTS: Six patients with MDS and four patients with JMML received a median of three and five cycles, respectively. Azacitidine 75 mg/m2 was well tolerated and plasma concentration-time profiles were similar to observed in adults. The most prevalent grade 3-4 adverse event was myelotoxicity. No responses were seen in patients with MDS, but 83% achieved stable disease; four patients underwent an allotransplant. Overall response rate in the JMML cohort was 75% (two complete responses; one partial response) and all responders underwent hematopoietic stem cell transplantation. One-year overall survival was 67% (95% confidence interval 38-100) in MDS and 50% (95% confidence interval 19-100) in JMML.

CONCLUSIONS: Azacitidine 75 mg/m2 prior to a second hematopoietic stem cell transplantation is safe in children with relapsed MDS/JMML. Although the long-term advantage remains to be assessed, this study suggests that azacitidine is an efficacious option for relapsed JMML.


Original languageEnglish
Pages (from-to)719-728
Number of pages10
JournalPaediatric drugs
Issue number6
Publication statusPublished - 2023


  • Adult
  • Humans
  • Child
  • Azacitidine/adverse effects
  • Leukemia, Myelomonocytic, Juvenile/drug therapy
  • Myelodysplastic Syndromes/drug therapy
  • Remission Induction
  • Hematologic Neoplasms
  • Leukemia, Myeloid, Acute/chemically induced


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