ORAL MUCOSITIS IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA AFTER HIGH-DOSE METHOTREXATE TREATMENT WITHOUT DELAYED ELIMINATION OF METHOTREXATE - RELATION TO PHARMACOKINETIC PARAMETERS OF METHOTREXATE

Oral mucositis is a common problem after high-dose methotrexate (HD-MT X) treatment. Our purpose was to identify factors associated with the development of mucositis in children with ALL who had no delayed elimi nation of methotrexate (MTX) according to the conventional criteria (p -MTX at 42 hours < 1 mu mol/L and at 66 hours < 0.2 mu mol/L). Pharmac okinetic studies of MTX and the metabolite 7-hydroxymethotrexate (7-OH MTX) in plasma and saliva were carried out in 13 children treated with HD-MTX (5-8 g/m(2) intravenously over 24 hours for a total of 44 cour ses). Oral mucositis was evaluated according to the criteria of the Wo rld Health Organization. Mucositis was observed in 52% of the infusion s. In 28 infusions with no delayed elimination of MTX 39% developed mu cositis, which was found to correlate significantly with low systemic clearance of MTX during the infusion and a low p-7-OHMTX/p-MTX ratio a t 66 hours after the start of infusion. The MTX concentration in saliv a did not show any correlation with the development of mucositis. The present conventional criteria for high-risk MTX concentrations might n eed to be reevaluated because a high percentage of patients still suff er from oral toxicity despite ''normal'' elimination. A reduced ratio between the simultaneous concentrations of 7-OHMTX and MTX in plasma m ay be a possible mechanism of this ''unpredictable'' oral toxicity.