Antimetabolite dose intensity and adverse outcomes in children with acute lymphoblastic leukemia: a COG-AALL03N1 report

•High antimetabolite dose intensity during maintenance therapy for childhood ALL is associated with elevated odds of hematologic toxicities.•Among those who adhere to 6-mercaptopurine, high antimetabolite dose intensity is associated with significantly elevated hazard of relapse. [Display omitted] T...

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Bibliographic Details
Published in:Blood 2024-11, Vol.144 (22), p.2327-2335
Main Authors: Wadhwa, Aman, Chen, Yanjun, Hageman, Lindsey, Angiolillo, Anne, Dickens, David S., Neglia, Joseph P., Ravindranath, Yaddanapudi, Termuhlen, Amanda, Wong, F. Lennie, Landier, Wendy, Bhatia, Smita
Format: Article
Language:English
Subjects:
Adolescent
Antimetabolites, Antineoplastic - administration & dosage
Antimetabolites, Antineoplastic - adverse effects
Antimetabolites, Antineoplastic - therapeutic use
Child
Child, Preschool
Female
Humans
Infant
Male
Medication Adherence - statistics & numerical data
Mercaptopurine - administration & dosage
Mercaptopurine - adverse effects
Mercaptopurine - therapeutic use
Methotrexate - administration & dosage
Methotrexate - adverse effects
Methotrexate - therapeutic use
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
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Summary:•High antimetabolite dose intensity during maintenance therapy for childhood ALL is associated with elevated odds of hematologic toxicities.•Among those who adhere to 6-mercaptopurine, high antimetabolite dose intensity is associated with significantly elevated hazard of relapse. [Display omitted] The association between antimetabolite dose intensity (DI) and adverse events among children receiving maintenance therapy for acute lymphoblastic leukemia (ALL) remains unclear, especially in the context of antimetabolite adherence. Using Children’s Oncology Group AALL03N1 data, we examined the association between high DI during the first 4 study months and (i) treatment-related toxicities during the subsequent 2 study months; and (ii) relapse risk. Patients were classified into a high DI phenotype (either 6-mercaptopurine [6-MP] or methotrexate [MTX] DI ≥110% during the first 4 study months, or 6-MPDI or MTXDI 100%-110% at study enrollment and ≥25% increase over the 4 study months) and normal DI phenotype (all others). Only patients with wild-type TPMT and NUDT15 were included. 6-MP adherence data were available for 63.7% of study participants and used to stratify as adherent (median adherence ≥85%) and nonadherent (median adherence
ISSN:0006-4971
1528-0020
1528-0020
DOI:10.1182/blood.2024024455