Methotrexate-associated toxicity during therapy of acute lymphoblastic leukemia in children with Down syndrome

Background:

Children with Down syndrome (trisomy 21) bear a 30-times higher risk of acquiring an acute lymphoblastic leukemia (ALL) compared to the overall pediatric population. During chemotherapy many Down syndrome ALL patients (DS-ALL) suffer from severe side effects after application of high dose methotrexate (HD-MTX). This requires a dose reduction, which may lead to an impaired outcome. However, severity of side effects differs distinctively among DS-ALL questioning the need of a general a priori dose reduction for this patient cohort.

Methods:

To shed light on this discrepancy, we investigated data of 103 DS-ALL patients from three consecutive BFM-ALL trials with regard to toxicity after HD-MTX administration. Furthermore, the influence of the G80A polymorphism (rs1051266) of RFC1/SLC19A1 on MTX toxicity was investigated, since this carrier is the main transporter for MTX into cells and rs1051266 affects the transportation rate.

Results:

MTX dose reduction attenuates side effects to some extent, but still high levels of toxicity are observed. rs1051266 is not associated with the severity of toxicity.