HLA‒B*58:01 and skin reactions in pediatric hematology and oncology patients treated with allopurinol

Abstract

Background: Allopurinol is widely used to prevent hyperuricemia in patients with tumor lysis syndrome. However, its use can trigger severe cutaneous adverse reactions (SCARs) with a mortality rate of approximately 11.39%. The human leukocyte antigen (HLA)–B*58:01 genotype is a major risk factor for SCARs. Although most studies to date have examined HLA–B*58:01 in Thai adults, data on pediatric patients are limited. Purpose: Here we aimed to evaluate the association between HLA-B*58:01 and skin reactions in children with hematological or oncological diagnoses receiving allo-purinol and determine its prevalence in this population. Methods: Pediatric patients (age≤18 years) with hemato-logical or oncological diseases who received allopurinol were enrolled in this cross-sectional study of previously exposed and newly prescribed cases. HLA-B*58:01 geno-typing was performed to assess its association with skin reactions. Results: A total of 108 patients (mean age, 9.3 years) were included. Most patients (n=93, 86.1%) received allopurinol as prophylaxis for tumor lysis syndrome. Of them, 75 (69.4%) received allopurinol concomitantly with chemo-therapy for malignancies, whereas the remaining patients received allopurinol during conditioning for hemato-poie tic stem cell transplantation. The prevalence of HLA–B*58:01 positivity was 17.6% (n=19 of 108 patients). The median exposure duration was 5 days (range, 1-19 days). No HLA–B*58:01–positive patients experienced a skin reaction. However, one patient who tested negative for HLA-B*58:01 developed a maculopapular rash on day 2 of the allopurinol therapy and required intravenous antihistamines. Conclusion: Short-duration allopurinol exposure likely mitigates the risk of SCARs regardless of HLA–B*58:01 status. Routine HLA-B*58:01 testing may not be warranted in pediatric patients receiving brief allopurinol courses. However, larger studies are required to confirm these findings.