KEY TAKEAWAYS
- The study aimed to assess allopurinol’s role in reducing 6-MMPN-associated toxicities during pediatric ALL and LLy patients’ maintenance therapy.
- The primary endpoint was to determine ANC prior to and after initiation of allopurinol.
- Researchers concluded that the use of allopurinol in pediatric ALL and LLy patients receiving mercaptopurine during maintenance therapy is deemed safe and effective.
Tecca Barone and his team aimed to assess the safety and efficacy of allopurinol in pediatric patients with acute lymphoblastic leukemia (ALL) and lymphoma (LLy) undergoing mercaptopurine maintenance therapy.
The myelosuppressive and immunosuppressive effects associated with 6-thioguanine nucleosides (6-TGN) and the toxicities linked to 6-methylmercaptopurine (6-MMPN), such as hepatotoxicity, pancreatitis, and hypoglycemia, pose challenges in pediatric patients. Past research suggests that the addition of allopurinol might offer a potential solution to mitigate these toxicities.
They performed an inclusive analysis with the primary endpoint focusing on the duration within the target ANC before and after allopurinol initiation. Secondary endpoints included ameliorating specific toxicities (hepatotoxicity, pancreatitis, and hypoglycemia), alterations in the 6-MMPN to 6-TGN ratio, and an exploratory assessment of mercaptopurine daily dose reduction. 16 eligible patients were identified, with 15 (94%) included in the study. The median percentage of maintenance days within the target ANC increased from 27.8% (IQR 22.6-44.9) before allopurinol initiation to 41.6% (IQR 20.2-58.2) after initiation.
All patients experienced selective toxicities, including hepatotoxicity 15 (100%), pancreatitis 1 (7%), and hypoglycemia 3 (20%). Improvement in toxicities was observed in 13/15 (87%), 1/1 (100%), and 2/3 (67%) of cases, respectively. The average 6-MMPN:6-TGN ratio decreased from 304:1 before allopurinol initiation to 15:1 after initiation, reflecting a 95% reduction. Moreover, the average mercaptopurine dose decreased by approximately 56% (from 63 to 28 mg/m2/day) before and after allopurinol initiation.
The study concluded that the utilization of allopurinol in pediatric patients undergoing maintenance therapy for ALL and LLy with mercaptopurine is safe and effective.
The study is sponsored by Pennsylvania State University
Source: https://pubmed.ncbi.nlm.nih.gov/38351548/
Barone T, Dandekar S, McKeone D, et al. (2024). “Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with Acute Lymphoblastic Leukemia and Lymphoma during maintenance therapy.” Cancer Rep (Hoboken). 2024 Feb;7(2):e1987. doi: 10.1002/cnr2.1987. PMID: 38351548; PMCID: PMC10864713.
