ArticleBlood2024
Antimetabolite dose intensity and adverse outcomes in children with acute lymphoblastic leukemia: a COG-AALL03N1 report.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Chicken biliary exosomes ameliorate lipopolysaccharide-induced hepatocyte injury.Scientific reports · 2026Article
- Global Challenges in Paediatric Acute Lymphoblastic Leukaemia.Acta haematologica · 2026Review
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Authors and funding
11 authors.
Funding
Abstract
abstractThe 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 <85%) participants. Multivariable analyses were adjusted for sociodemographic and clinical prognosticators. Of the 644 patients, 29.3% were exposed to high DI. High DI was associated with a 2.1-fold greater odds of hematologic toxicity (95% confidence interval [CI] = 1.4-3.1; reference: normal DI) in the entire cohort and 2.9-fold higher among adherers (95% CI = 1.6-5.1); odds were comparable among nonadherers (2.1-fold; 95% CI = 0.4-10.1). Although high DI was not associated with relapse in the entire cohort (adjusted hazard ratio [aHR] = 1.4; 95% CI = 0.8-2.4), it was associated with a greater hazard of relapse among adherent participants (aHR = 2.4; 95% CI = 1.0-5.5) but not among nonadherent participants (aHR = 0.9; 95% CI = 0.2-3.8). Dose escalation above protocol doses during maintenance therapy for ALL should be done cautiously after assessing adherence to prescribed therapy.
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