We were pleased to receive Dr. Africa Garcia Orad’s comments regarding our article on methotrexate toxicity in paediatric acute lymphoblastic leukaemia. The great inter-individual variability in drug effects and efficacy is one of the major issues in the clinical management of paediatric patients with cancer, and the severe toxicity is often the treatment’s major limitation. Therefore, we focused our study on toxicity difference between two treatment groups relative to MTHFR polymorphisms. In fact, in our opinion, the reanalysis with the odds ratios performed by Africa Garcia Orad et al. is controversial because in 5 g/m2 group are included both high risk and standard/intermediate risk T-cell ALL that represent a different clinical entity with different outcome. For this reason, we have preferred to focus our data in the toxicity between both groups in order to evaluate the possible correlation between MTHFR genotype and toxicity. This consideration is related to that the total number cases between 2 and 5 g/m2 groups is not significantly different (P = 0.1). The aim of our study was to know whether the MTHFR genotype could be associated with different toxicity.

We agree that the number of our patients studied produced little subgroups considering the two different MTX dosages. Therefore, the confirmation of these results in a larger prospective study is needed to draw recommendations with respect to dose adjustment and establish the efficacy of MTX treatment according to MTHFR polymorphisms.