Identification of residual disease followed by trade-off analysis between drug optimisation, MRD and sustenance of normal haematopoiesis under maintenance chemotherapy in childhood ALL

ALL, an acute lymphoblastic leukaemia commonly occurring cancer in children, relapses in many cases. Hence to remove (minimal) residual leukaemia or disease (MRD), a maintenance chemotherapy schedule is conducted for two years after intensive chemotherapy. MRD detection occasionally fails due to mutability behaviour of leukemic cells or their aberrant marker expression and presence of MRD in very minor amount enhances the chances of disease relapse in long-term. Application of higher drug dose during maintenance phase could remove MRD but produces drug related toxicity. Bone marrow biopsy is required for MRD detection. Here, a peripheral blood-based control theoretic model is proposed to detect the presence of MRD. Moreover, the model-based eigenvalue and trade-off analysis could provide a guidance in clinical decision making to optimise the maintenance chemotherapeutic regime (both dose and duration) for individual ALL patients.

Automated summary

Acute lymphoblastic leukemia (ALL), a common cancer in children, often relapses. Maintenance chemotherapy is conducted to remove minimal residual disease (MRD) after intensive chemotherapy, but MRD detection sometimes fails due to the mutability behavior of leukemic cells or their aberrant marker expression. Higher drug doses during maintenance phase can remove MRD but may cause drug-related toxicity. This study proposes a control theoretic model using peripheral blood to detect MRD and also provides guidance in optimizing maintenance chemotherapeutic regime for individual ALL patients.