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Allopurinol Use During Pediatric Acute Lymphoblastic Leukemia Maintenance Therapy Safely Corrects Skewed 6-Mercaptopurine Metabolism, Improving Inadequate Myelosuppression and Reducing Gastrointestinal Toxicity by Gordon Cohen; Stacy Cooper; Edward Allan Sison; Colleen Annesley; Mariam Bhuiyan; Patrick Brown is a Medicine article available to read on EtoBox.

What is Allopurinol Use During Pediatric Acute Lymphoblastic Leukemia Maintenance Therapy Safely Corrects Skewed 6-Mercaptopurine Metabolism, Improving Inadequate Myelosuppression and Reducing Gastrointestinal Toxicity about?

## 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

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Author

Gordon Cohen; Stacy Cooper; Edward Allan Sison; Colleen Annesley; Mariam Bhuiyan; Patrick Brown

Publisher

Wiley

Published

2020

Language

EN

Field

Medicine (Health Sciences)