title: 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).
authors: Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University , Lucknow , India.
authors: Nirmalya
authors: N
authors: Roy Moulik
authors: Archana
authors: A
authors: Kumar
authors: Suraksha
authors: S
authors: Agrawal
authors: Shally
authors: S
authors: Awasthi
authors: Abbas Ali
authors: AA
authors: Mahdi
authors: Ashutosh
authors: A
authors: Kumar
mesh_terms: D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D010597:Pharmacogenetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Folate; MTHFR; childhood ALL; induction deaths