70P - Individualising methotrexate dose based on MTHFR gene polymorphisms in acute lymphoblastic leukemia

Background

Methotrexate is an important component of acute lymphoblastic leukemia (ALL) protocols and methotrexate toxicity can at times lead to fatal complications which are unpredictable. Understanding gene polymorphisms is important as antidote to toxicity is not widely available and febrile neutropenia is deadly for patients with remote access to health care system in developing counties. This study was undertaken to analyse the toxicities in patients receiving high dose methotrexate and their association with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms.

Methods

MTHFR gene polymorphisms (A1298C & C677T) were analysed using real time polymerase chain reaction on peripheral blood of patients with acute lymphoblastic leukemia receiving high dose methotrexate (HDMTx, methotrexate > 500 mg per square meter) and methotrexate toxicities were analysed. Statistical analysis was done by chi-square test.

Results

A total of 51patients received high dose methotrexate therapy, out of which 27 patients had MTHFR gene polymorphisms and 24 patients had no polymorphisms. Grade3 and 4 toxicities were seen in 16 of 51 patients (31%) of which 14patients (87.5%) had gene polymorphisms and 2 patients had no polymorphisms. All patients with toxicities having polymorphisms were heterozygous, A1298C in 9patients (64%), C677T in 5 patients (35%). Homozygous polymorphisms were not seen in any patient. A significant association was seen between MTHFR gene polymorphisms and methotrexate toxicity (p-value 0.000828) compared to those without polymorphisms.

Conclusions

Testing for MTHFR gene polymorphisms is important before starting high dose methotrexate as these patients need to be monitored carefully and dose adjustments need to be done to prevent morbidity and unpredictable mortality.

Editorial acknowledgement

Clinical trial identification

NA

Legal entity responsible for the study

NIMS, Hyderabad.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.