A Retrospective Review of Mercaptopurine Metabolism Reveals High Rate of
Patients with Suboptimal Metabolites Successfully Corrected with
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.