Prediction of Acute Lymphoblastic Leukemia Maintenance Therapy

Introduction: The importance of maintenance therapy with 6-mercaptopurine and methotrexate in childhood acute lymphoblastic leukemia is well established. Drug doses are adjusted according to target white cell counts to achieve sustained antileukemic activity while avoiding excessive myelosuppression. However, the optimal dosing strategy is unknown and individual responses to dose adjustments are heterogeneous. We aimed to create a model to predict dose responses and therefore allow advanced dose adjustment.

Methods: Maintenance therapy data from 107 children treated in two centers according to BFM 2000 and 2009 protocols was analyzed. While excessive white cell suppression, anemia, and thrombocytopenia are rare, 73% of patients have insufficient total white cell suppression during > 50% of their maintenance therapy.

Results: The generated model shows that the overall correlation between drug doses and white cell lines' counts is poor. The influence of dose changes on total white cells, neutrophils, and lymphocytes is most pronounced after a delay of 3 – 5, 4 – 5, and 3 – 5 weeks, respectively. Consideration of these findings allows more informed dose adjustments in maintenance therapy.