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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, Erin M; Kairalla, John A; Devidas, Meenakshi; Hibbitts, Emily; Carroll, Andrew J; Heerema, Nyla A; Kubaney, Holly R; August, Margaret A; Ramesh, Sidharth; Yoo, Byunggil; Farooqi, Midhat S; Pauly, Melinda G; Wechsler, Daniel S; Miles, Rodney R; Reid, Joel M; Kihei, Cynthia D; Gore, Lia; Raetz, Elizabeth A; Hunger, Stephen P; Loh, Mignon L; Brown, Patrick A.
Afiliação
  • Guest EM; Division of Hematology, Oncology, Bone Marrow Transplant, Children's Mercy Kansas City, University of Missouri-Kansas City School of Medicine, Kansas City, MO. eguest@cmh.edu.
  • Kairalla JA; Department of Biostatistics, University of Florida, Gainesville, FL.
  • Devidas M; St. Jude Children's Research Hospital, Memphis, TN.
  • Hibbitts E; Department of Biostatistics, University of Florida, Gainesville, FL.
  • Carroll AJ; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL.
  • Heerema NA; Department of Pathology, The Ohio State University, Columbus, OH.
  • Kubaney HR; Dell Children's Medical Center of Central Texas, Austin, TX.
  • August MA; Health Informatics and Technology, Children's Mercy Kansas City, Kansas City, MO.
  • Ramesh S; University of Pennsylvania, Philadelphia, PA.
  • Yoo B; Research Informatics, Children's Mercy Kansas City, Kansas City, MO.
  • Farooqi MS; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, University of Missouri-Kansas City School of Medicine, Kansas City, MO.
  • Pauly MG; Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta and Emory University, Atlanta, GA.
  • Wechsler DS; Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta and Emory University, Atlanta, GA.
  • Miles RR; University of Utah, Department of Pathology, Salt Lake City, UT.
  • Reid JM; Mayo Clinic, Rochester, MN.
  • Kihei CD; Saint Mary's Hospital, West Palm Beach, FL.
  • Gore L; Children's Hospital Colorado, Center for Cancer and Blood Disorders, Denver, CO.
  • Raetz EA; New York University Langone Health, New York, NY.
  • Hunger SP; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
  • Loh ML; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute and the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, 98105.
  • Brown PA; Bristol Myers Squibb, Princeton, NJ.
Haematologica ; 2024 Jun 13.
Article em En | MEDLINE | ID: mdl-38867582
ABSTRACT
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.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Haematologica Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Haematologica Ano de publicação: 2024 Tipo de documento: Article