A Retrospective Review of Mercaptopurine Metabolism Reveals High Rate of Patients With Suboptimal Metabolites Successfully Corrected With Allopurinol

Lauren M Vasta; Richard C Zanetti; Dina S Parekh; Anne B Warwick; Kenneth Lieuw

doi:10.1097/MPH.0000000000001939

A Retrospective Review of Mercaptopurine Metabolism Reveals High Rate of Patients With Suboptimal Metabolites Successfully Corrected With Allopurinol

J Pediatr Hematol Oncol. 2021 Oct 1;43(7):e1003-e1009. doi: 10.1097/MPH.0000000000001939.

Authors

Lauren M Vasta^{1

2}, Richard C Zanetti^{1

2}, Dina S Parekh¹, Anne B Warwick³, Kenneth Lieuw^{1

3}

Affiliations

¹ Department of Pediatric Hematology and Oncology.
² National Capital Consortium, Walter Reed National Military Medical Center.
³ Uniformed Services University of Health Sciences, Bethesda, MD.

PMID: 32925411
DOI: 10.1097/MPH.0000000000001939

Abstract

Skewed drug metabolism of 6-mercaptopurine (6-MP) can jeopardize antileukemic effects and result in toxicities during the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Allopurinol can alter 6-MP metabolism to maximize therapeutic effects while reducing toxicities. Over 75% of our patients with acute lymphoblastic leukemia or lymphoblastic lymphoma experienced a 6-MP-related toxicity. Review of metabolite date a showed 6-methylmercaptopurine nucleotide levels were >10,000 in 55% of the cohort, suggesting 6-MP shunting. Allopurinol was initiated in 12 of 23 shunters with resolution of toxicities. We propose an algorithm to incorporate allopurinol into chemotherapy regimens for patients with inappropriate 6-MP metabolism.

Publication types

Clinical Trial

MeSH terms

Adolescent
Adult
Algorithms*
Allopurinol / pharmacology*
Antimetabolites
Antimetabolites, Antineoplastic / administration & dosage
Antimetabolites, Antineoplastic / adverse effects
Antimetabolites, Antineoplastic / metabolism
Child
Child, Preschool
Drug Therapy, Combination
Drug-Related Side Effects and Adverse Reactions / etiology
Drug-Related Side Effects and Adverse Reactions / metabolism
Drug-Related Side Effects and Adverse Reactions / pathology
Drug-Related Side Effects and Adverse Reactions / prevention & control*
Female
Follow-Up Studies
Humans
Infant
Infant, Newborn
Lymphoma, Non-Hodgkin / drug therapy*
Lymphoma, Non-Hodgkin / metabolism
Lymphoma, Non-Hodgkin / pathology
Male
Mercaptopurine / administration & dosage*
Mercaptopurine / adverse effects
Mercaptopurine / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
Prognosis
Retrospective Studies
Young Adult

Substances

Antimetabolites
Antimetabolites, Antineoplastic
Allopurinol
Mercaptopurine