Toxicities during therapy with high doses of methotrexate in children with acute lymphoblastic leukemia

Abstract

Intensification of systemic chemotherapy with in- clusion of high doses methotrexate (MTX) has contributed to the improvement of event-free survival in children with acute lymphoblastic leukemia (ALL). Despite this benefit, this agent might cause serious toxicity, even life-treating events during treatment. Therefore, prediction, early detection and management of toxic effects during therapy with high doses of MTX is still a great challenge for every pediatric oncologist.

The aim of our study was to evaluate the incidence of toxic effects of chemotherapy with high doses of MTX (5 g/m^2) and to compare them with toxicity during application of lower doses of MTX (2 g/m^2).

Retrospective record review of 77 children with medium risk ALL was done. Patients were treated in the Department of hematology and oncology at the University children's hospital in Skopje. Forty-five of them were treated with 5 g/m2 and 32 of them were treated with 2 g/m^2 (historic group). Toxicity was registered according to the protocol for acute toxicity, part of the ALL BFM 95 protocol.

Toxic effects were predominant in the group treated with higher doses of MTX. The  most significant toxic  effects were hepatotoxicity, oral mucositis and myelosuppression.  More  severe grade of hepatotoxicity and oral mucositis were present in the study group. In our study toxic  effects were more common in the study group due to application of higher doses of MTX.

Variations in toxicity between the patients of the study group are probably due  to the genetic differences in the drug absorption, their excretion and cellular transport. Current studies are dedicated on discovering genetic markers which will  be able  to predict the risk  of appearance of MTX toxicity.