Dose escalation intolerance disrupts maintenance therapy of children with ALL

Only a few children with acute lymphoblastic leukaemia (ALL) treated with mercaptopurine (6MP) and methotrexate (MTX) complete their maintenance therapy without interruptions at the current dose escalation schedules outlined by the Children’s Oncology Group protocols, a study has shown.

“The interruptions are due in part to intolerance of dose escalations of MTX and 6MP above 100 percent,” the authors said.

A retrospective chart review was conducted involving 77 children with ALL (median age 4.5 years). The authors collected data on time to first interruption and dose, as well as the total number of interruptions. Absolute neutrophil and platelet counts were recorded at time of interruption.

The authors completed the subgroup analysis of age, sex, diagnosis, and risk stratification, and gained approval by the Research Ethics Board. They also used Strata software to report descriptive statistics.

Only nine of the 77 patients analysed had no treatment interruptions during maintenance therapy. The mean number of interruptions during maintenance therapy was 3.2, while the mean time to first interruption was 149.8 days. At first interruption, the mean dose percent of MTX and 6MP was 94.4 percent and 106 percent, respectively.

Subgroup analysis revealed that maintenance therapy was interrupted regardless of age, sex, diagnosis, or disease risk stratification.

“Future research should investigate doses of 6MP and MTX in maintenance therapy in relation to leukaemia outcomes,” the authors said.

MTX and 6MP cause myelosuppression and interruptions in therapy in children with ALL. Length of time off therapy is associated with poorer outcomes, according to the authors.