Azacitidine appears to be safe for use among infants with acute lymphoblastic leukemia (ALL) with a KMT2A rearrangement (KMT2A-r) undergoing chemotherapy, according to a pilot trial presented at the 2021 American Society of Pediatric Hematology/Oncology (ASPHO) meeting. However, they noted 2 grade 4 dose-limiting toxicities (DLTs).

Among infants with ALL, KMT2A-r is associated with chemoresistance, early relapse, and a poor prognosis. ALL blasts in this setting show DNA hypermethylation, which may explain this correlation.

Azacitidine is a hypomethylating agent that has shown promise both in adult patients with myelodysplastic syndrome and pediatric patients with leukemia. For this Children’s Oncology Group (COG) pilot trial ( Identifier: NCT02828358), researchers evaluated the safety and efficacy of this epigenetic primer among infants undergoing standard chemotherapy for KMT2A-r ALL.

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Between 2017 and 2019, patients received 4 treatment courses of intravenous azacitidine 2.5 mg/kg (10- to 40-minute intervals over 5 days) following induction chemotherapy. The authors predefined a DLT as any grade 5 event or any grade 3-4 event leading to treatment delay within the first 3 azacitidine treatment-courses.

Overall, of the 78 patients initially enrolled to the study, 56 (72%) had KMT2A-r ALL. A total of 31 patients completed at least 3 treatment courses and were evaluable for DLTs, while 25 were not evaluable.

A total of 2 patients (6%) had a DLT, both of which were grade 4 neutropenia; these DLTs led to at least a 4-week delay in treatment. Other toxicities were described as expected for patients undergoing standard chemotherapy for ALL, and were not reported.

“Azacitidine is safe and well tolerated in infants receiving standard chemotherapy for ALL,” the authors wrote. “Future studies are necessary to test the efficacy of this treatment strategy.”


Guest E, Kairalla J, Devidas M, et al. Azacitidine as epigenetic priming for chemotherapy is safe in infants with KMT2A-rearranged ALL. Paper presented at: 2021 American Society of Pediatric Hematology/Oncology (ASPHO) Conference; April 20-23, 2021; virtual.