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-MTX42h) and 66 (p-MTX66h) h, absolute neutrophil count (ANC) <= or > 1.0 x 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-MTX42h >= 1.0 mu mol/l had an odds ratio (OR) of 4.3 of developing oral mucositis when compared with the referent group of children who had p-MTX42h < 1.0 mu mol/l. Children with p-MTX66h >= 0.2 mu mol/l had an OR of 8.2 of developing oral mucositis when compared with the referent group of children who had p-MTX66h < 0.2 mu mol/l. Children with ANC <= 1.0 x 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 x 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.