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A Retrospective Review of Mercaptopurine Metabolism Reveals High Rate of Patients with Suboptimal Metabolites Successfully Corrected with Allopurinol
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  • Lauren Vasta,
  • Richard Zanetti,
  • Dina Parekh,
  • Anne Warwick,
  • Kenneth Lieuw
Lauren Vasta
WRNMMC
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Richard Zanetti
WRNMMC
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Dina Parekh
WRNMMC
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Anne Warwick
Uniformed Services University of the Health Sciences F Edward Hebert School of Medicine
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Kenneth Lieuw
WRNMMC
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Abstract

Background: 6-Mercaptopurine (6-MP) is the most frequently used chemotherapy agent in the management of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Skewed drug metabolism can decrease the effectiveness of 6-MP and result in unnecessary toxicities. Current guidelines suggest holding or lowering 6-MP doses with toxicity; however, this approach results in decreased intensity of 6-MP treatment, potentially risking disease relapse. Allopurinol can alter 6-MP metabolism to maximize therapeutic effects while reducing adverse toxicities. Methods: This single institution, retrospective cohort study, quantified the incidence of mercaptopurine related toxicities and the number of mercaptopurine metabolite shunters. For those patients started on allopurinol, we collected clinical follow up information. Results: Of 42 eligible patients, 74% and 88% had at least one episode of hypoglycemia and elevated alanine aminotransferase (ALT), respectively. Mercaptopurine metabolite data were available in 66% of our patients. 6-methylmercaptopurine nucleotide (6-MMPN) levels were >10 000 in 55% of the cohort, suggesting 6-MP shunting. Allopurinol was initiated for metabolite and laboratory derangements in 12 of 23 shunters. All patients who received allopurinol had resolution of toxicities. Discussion: In our population of children and young adults treated for ALL and LL, we found a high incidence of shunters, many with associated toxicities. The patients who received allopurinol in combination with scheduled chemotherapy showed reversal of undesired toxicities, suggesting combination therapy may be beneficial for certain patients. Based on our institutional experience, we propose an algorithm to incorporate allopurinol into chemotherapy regimens for patients with ALL or LL who have inappropriate 6-MP metabolism.

Peer review status:Published

09 Sep 2020Published in Journal of Pediatric Hematology/Oncology volume Publish Ahead of Print. 10.1097/MPH.0000000000001939