CAR-T Cell Therapy for the Treatment of ALL: Eradication Conditions and In Silico Experimentation

In this paper, we explore the application of Chimeric Antigen Receptor (CAR) T cell therapy for the treatment of Acute Lymphocytic Leukaemia (ALL) by means of in silico experimentation, mathematical modelling through first-order Ordinary Differential Equations and nonlinear systems theory. By combining the latter with systems biology on cancer evolution we were able to establish a sufficient condition on the therapy dose to ensure complete response. The latter is illustrated across multiple numerical simulations when comparing three mathematically formulated administration protocols with one of a phase 1 dose-escalation trial on CAR-T cells for the treatment of ALL on children and young adults. Therefore, both our analytical and in silico results are consistent with real-life scenarios. Finally, our research indicates that tumour cells growth rate and the killing efficacy of the therapy are key factors in the designing of personalised strategies for cancer treatment.

Severe multiorgan toxicity after first dose of Capizzi methotrexate in a young adult patient with acute lymphocytic leukaemia

Methotrexate is a versatile antineoplastic and immunosuppressive agent. We report a case of a young adult on the Cancer and Leukaemia Group B 10403 treatment protocol for B-cell acute lymphoblastic leukaemia. She has previously completed the induction and consolidation phases with good tolerance then started on Capizzi methotrexate during the interim maintenance phase. Few days after receiving one intermediate dose of methotrexate, she developed severe multiorgan toxicities including pancytopaenia and several dermatologic toxicities. The patient underwent extensive diagnostic workup, with all results negative, pointing eventually towards severe methotrexate toxicity. This case highlights the broad spectrum of toxicities that can occur even with low doses of methotrexate. Capizzi methotrexate therapy implies no leucovorin therapy, hence putting patients at risk for multiorgan toxicity. Our experience reinforces the importance of close monitoring for patients receiving methotrexate, regardless of dose, and the prompt administration of high-dose leucovorin once toxicity suspected.