Minimal residual disease predicts outcomes in <i>KMT2A</i>‐rearranged but not <i>KMT2A</i>‐germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631

Faulk, Kelly E; Kairalla, John A.; Dreyer, ZoAnn E.; Carroll, Andrew J.; Heerema, Nyla A.; Devidas, Meenakshi; Carroll, William L.; Raetz, Elizabeth A.; Loh, Mignon L.; Hunger, Stephen P.; Borowitz, Michael J.; Wang, Cindy; Guest, Erin; Brown, Patrick

doi:10.1002/pbc.30467

Cited by 2 publications

(1 citation statement)

References 14 publications

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“…This finding is consistent with other trials of KMT2A-r infant ALL. 5,[42][43][44] Considering that the survival of patients with negative MRD following induction, consolidation, and interim maintenance was still unacceptably poor, future trials should evaluate other MRD methodologies, such as highthroughput sequencing, to better classify response among infants. It is imperative to improve upon the sensitivity and predictive value of residual disease detection in infants, to facilitate allocation of infants at highest risk of treatment failure or relapse to novel therapies.…”

Section: Discussionmentioning

confidence: 99%

Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia: Children’s Oncology Group trial AALL15P1

Guest,

Kairalla,

Devidas

et al. 2024

haematol

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Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of remission failure, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children’s Oncology Group trial AALL15P1 tested the safety and tolerability of five days of azacitidine immediately prior to the start of chemotherapy on day six, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was welltolerated, with only two of 31 evaluable patients (6.5%) experiencing dose-limiting toxicity. Whole genome bisulfite sequencing of peripheral blood mononuclear cells (PBMCs) demonstrated decreased DNA methylation in 87% of samples tested following five days of azacitidine. Event-free survival was similar to prior studies of newly diagnosed infant ALL. Azacitidine is safe and results in decreased DNA methylation of PBMCs in infants with KMT2A-r ALL, but the incorporation of azacitidine to enhance cytotoxicity did not impact survival. Clinicaltrials.gov identifier: NCT02828358.

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Section: Discussionmentioning

confidence: 99%