Role of folate status and methylenetetrahydrofolate reductase genotype on the toxicity and outcome of induction chemotherapy in children with acute lymphoblastic leukemia

Abstract

The effect of serum folate levels and methylenetetrahydrofolate reductase (MTHFR) genotype on complications and outcome of induction chemotherapy in 150 children with acute lymphoblastic leukemia (ALL) was studied. Folate deficiency in 26% at baseline was more common in children with MTHFR 677 mutations. Folate deficient children had a higher incidence of neutropenia (p = 0.03), thrombocytopenia (p = 0.02) and febrile neutropenia (p = 0.01) and higher transfusion requirement during induction compared to folate sufficient children. Sepsis related induction deaths were more frequent in folate deficient children (p = 0.02) during induction. Children with 677 and 1298 mutations had a higher incidence of cytopenias (p = 0.01) and mucositis (p = 0.007), the risks of which increased with concomitant folate deficiency. A significant fall in folate levels was observed post-induction (p = 0.02), most markedly in mutant 677 genotypes. Multivariate analysis revealed associations of baseline folate deficiency with low counts at day 14 (p = 0.001) and MTHFR 1298 mutations with mucositis (p = 0.02).

Keywords::

• Folate
• MTHFR
• childhood ALL
• induction deaths

Acknowledgements

The authors acknowledge the help of Sudhir Kumar Mondal, PhD, Statistical Consultant, Center for Bio-Medical Research, Lucknow, India for helping with the statistical analysis, Dr. Balraj Singh, MD, Assistant Professor, Department of Community Medicine, Indira Gandhi Medical College, Shimla, India for statistics related help during planning of the study, and the Uttar Pradesh Council of Science and Technology, Lucknow, India for funding the research (Grant number: CST/SERPD/D-373). Nirmalya Roy Moulik is supported by a post-doctoral fellowship from the Indian Council of Medical Research, New Delhi, India.

Potential conflict of interest:

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Supplementary material available online

Supplementary Table I showing association of pre-induction nutritional status and albumin levels with complications.