Association of plasma methotrexate, neutropenia, hepatic dysfunction, nausea/vomiting and oral mucositis in children with cancer

Oral mucositis is a major toxicity associated with high‐dose methotrexate (HD‐MTX) therapy in the treatment of children with acute lymphoblastic leukaemia and osteosarcoma. This pilot matched case–control study investigated the associations between plasma concentration of MTX at 42 (p‐MTX 42h ) and 66 (p‐MTX 66h ) h, absolute neutrophil count (ANC) ≤ or >1.0 × 10 9 /l, serum transaminases (ASAT/ALAT) < or ≥58 U/l, WHO < or ≥grade 2 nausea/vomiting and WHO < or ≥grade 2 oral mucositis. In this study, 11 children with WHO ≥grade 2 oral mucositis were compared with 17 control children matched for age, diagnosis and MTX‐dosage. The results indicated that children with p‐MTX 42h  ≥ 1.0 μmol/l had an odds ratio (OR) of 4.3 of developing oral mucositis when compared with the referent group of children who had p‐MTX 42h  < 1.0 μmol/l. Children with p‐MTX 66h  ≥ 0.2 μmol/l had an OR of 8.2 of developing oral mucositis when compared with the referent group of children who had p‐MTX 66h  < 0.2 μmol/l. Children with ANC ≤ 1.0 × 10 9 /l had an OR of 1.2 of developing oral mucositis when compared with the referent group of children who had ANC > 1.0 × 10 9 /l. In comparison with the referent group of children, who had <58 U/l ASAT/ALAT, those with ASAT/ALAT ≥ 58 U/l had an OR of 1.2 of developing oral mucositis. Finally, children with WHO grade ≥2 nausea/vomiting had an elevated risk of developing oral mucositis when compared with the referent group of children who had WHO grade <2 nausea/vomiting (OR = 8.7). In conclusion, the results in this preliminary study provide support for the hypothesis that the risk of oral mucositis is associated with the plasma MTX concentration at 66 h and the level of nausea/vomiting.