Peer-reviewed article
2448 The effect of allopurinol on pediatric patients undergoing maintenance chemotherapy for acute lymphoblastic leukemia or lymphoblastic lymphoma
Cohen G, Cooper S ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study examined whether adding allopurinol to standard chemotherapy improves treatment outcomes in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. Researchers tracked 13 pediatric patients receiving maintenance chemotherapy with 6-mercaptopurine and measured changes in drug dosing, liver toxicity, and metabolite levels after allopurinol was added. The results suggest allopurinol reduced the required chemotherapy dose, improved liver function, and improved the balance of toxic to active drug metabolites in most patients studied.
Key points
- 11 of 12 patients required significantly lower 6-MP doses after allopurinol was added (p<0.05)
- All 10 patients assessed showed lower toxic-to-active metabolite ratios (6MMP:6TGN) after allopurinol
- Goal metabolite ratios (<40) were maintained for significantly more weeks in 6 patients and near-significantly in 2 others after allopurinol addition
- 9 of 13 patients showed significantly greater weeks with normal liver enzyme levels (ALT<120) after allopurinol addition
- Further analysis was ongoing for bilirubin levels, absolute neutrophil count, infection-related hospital admissions, and therapy holds
Limitations
This is a single-arm pilot study with only 13 patients and no control group, making it impossible to determine if improvements are due to allopurinol or other factors. The study lacks long-term follow-up data on disease outcomes, survival rates, or overall treatment success.
Abstract
OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (p<0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.