Allopurinol use during pediatric acute lymphoblastic leukemia maintenance therapy safely corrects skewed 6-mercaptopurine metabolism, improving inadequate myelosuppression and reducing gastrointestinal toxicity
| Autor: | Mariam Bhuiyan, Edward Allan R. Sison, Stacy Cooper, Patrick Brown, Colleen Annesley, Gordon Cohen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Antimetabolites Gastrointestinal Diseases Maintenance Allopurinol Rome Gastroenterology Article Transaminase 03 medical and health sciences 0302 clinical medicine Maintenance therapy Internal medicine Medicine Humans Adverse effect Child Bone Marrow Diseases Retrospective Studies biology business.industry Mercaptopurine leukemia Infant Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Prognosis Survival Rate Oncology Alanine transaminase Child Preschool 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health Toxicity Absolute neutrophil count biology.protein Female Neoplasm Recurrence Local business Follow-Up Studies 030215 immunology medicine.drug |
| Zdroj: | Pediatric blood & cancer |
| ISSN: | 1545-5017 1545-5009 |
| Popis: | Background Inadequate myelosuppression during maintenance therapy for acute lymphoblastic leukemia (ALL) is associated with an increased risk of relapse. One mechanism is skewed metabolism of 6-mercaptopurine (6MP), a major component of maintenance therapy, which results in preferential formation of the hepatotoxic metabolite (6-methyl mercaptopurine [6MMP]) with low levels of the antileukemic metabolite, 6-thioguanine nucleotides (6TGN). Allopurinol can modify 6MP metabolism to favor 6TGN production and reduce 6MMP. Methods Patients in maintenance were considered for allopurinol treatment who had the following features: (a) Grade ≥3 hepatotoxicity; (b) Grade ≥2 nonhepatic gastrointestinal (GI) toxicity; or (c) persistently elevated absolute neutrophil count (ANC) despite >150% protocol dosing of oral chemotherapy. Results From 2013 to 2017, 13 ALL patients received allopurinol: nine for hepatotoxicity, five for inadequate myelosuppression, and three for nonhepatic GI toxicity (four met multiple criteria). Allopurinol was well tolerated, without significant adverse events. Allopurinol resulted in a significant decrease in the average 6MMP/6TGN ratio (mean reduction 89.1, P = .0001), with a significant increase in 6TGN (mean 550.4, P = .0008) and a significant decrease in 6MMP (mean 13 755, P = .0013). Patients with hepatotoxicity had a significant decrease in transaminase elevation after starting allopurinol (alanine transaminase [ALT] mean decrease 22.1%, P = .02), and all with nonhepatic GI toxicity had improved symptoms. Those with inadequate myelosuppression had a significant increase in the time with ANC in goal (mean increase 26.4%, P = .0004). Conclusions Allopurinol during ALL maintenance chemotherapy is a safe, feasible, and effective intervention for those who have altered metabolism of 6MP causing toxicity or inadequate myelosuppression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text