Background It is believed that allopurinol alters the metabolism of mercaptopurine in favour of 6-thioguanine nucleotide (6TGN), decreasing the production of 6-methyl-mercaptopurine (6MMP). 6TGN is responsible for leukocyte suppression, and 6MMP is associated with liver and pancreatic toxicity.
Purpose To evaluate the protective effect of low dose allopurinol on liver toxicity induced by mercaptopurine.
Material and methods We describe 3 cases of children with acute lymphoblastic leukaemia receiving maintenance treatment with daily mercaptopurine and weekly oral methotrexate according to ALL/SEHOP-PETHEMA-2013 protocol, that required interruptions due to hepatotoxicity secondary to mercaptopurine.
Results The 3 patients (2 boys 13 and 4 years old and 1 girl 3 years old) required discontinuation of treatment at 2, 19.8 and 13 weeks due to hepatotoxicity (ALT 15, 10.5 and 11.4 times above the upper limit of normal (×ULN); AST 8.4, 6.2 and 3.1×ULN, respectively). The treatment was restarted after 1 week with dose reduction to 25%, 95% and 55%. ALT was 6.1, 3 and 2.6×ULN, and AST 2.1, 1.8 and 0.9×ULN. After 16, 27 and 16 weeks of initiating maintenance treatment, allopurinol was added due to a new increase in ALT (8.1, 17.3 and 10.9×ULN) and AST (3.3, 5.7 and 4.1×ULN), with a dose of 30%, 75% and 55%, which were reduced to 25%, 50% and 28%, respectively. In the first patient, the same dose was maintained for the next 24 weeks with an ALT median of 0.59×ULN (range 0.3–4.0) and AST 0.7×ULN (range 0.5–2.9) and subsequently was increased to 37.5%. In the second, the dose was maintained for the next 11 weeks with an ALT median of 6.8×ULN (range 1.4–17.1) and AST 3.2×ULN (range 1.0–9.3). At 14 weeks, the dose was increased to 40% with an ALT median of 5.4×UNL (range 2.8–10.5) and AST 2.1×UNL (range 0.9–3.6), and at 25 weeks it was increased to 50%. In the third patient, the dosage was increased every 2 weeks for the next 5 weeks (40% and 55%) with an ALT median of 8.5×ULN (range 3.6–11.4) and AST 2.8×ULN (range 1.2–4.1).
Conclusion Addition of allopurinol to mercaptopurine allowed better tolerance to the treatment without new episodes of hepatotoxicity and with appropriate myelosuppression.
References and/or acknowledgements Zerra P, et al. Maintenance treatment with low-dose mercaptopurine in combination with allopurinol in children with acute lymphoblastic leukaemia and mercaptopurine-induced pancreatitis. Pediatr Blood Can2016;63:712–15.
No conflict of interest
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