[Studies on high-dose methotrexate with citrovorum factor rescue therapy in children: analysis of bone marrow cell...

Nine children in remission from hematologic malignancies received infusion of methotrexate (2,000-6,000 mg/m2) for 24 hours followed by citrovorum factor rescue (beginning 36 hours after the start of MTX infusion). Marrow cell kinetics of these patients were studied by flow cytometry with computer analysis. An accumulation of cells in the early-mid S phase and a decrease of cells in the G2/M phase were observed at 24-48 hours after exposure to MTX except for one infant case. By the 6th day after MTX infusion, the DNA histograms returned to pretreatment values. No kinetic perturbation was observed in the marrow cells of a 1-year, 5-month-old infant who showed high plasma MTX concentrations over the median values of the other eight children. These results show that profound but reversible changes are observed in marrow cell kinetics in most patients treated with our current high-dose MTX therapy with CF rescue and that a repeated course would be possible without cumulative marrow toxicity. More studies in young infants are needed to clarify the relationship between age and marrow toxicity of MTX so that treatment schedules with a higher therapeutic index can be designed.