Impact of DARC, GSDMA and CXCL2 polymorphisms on induction toxicity in children with acute lymphoblastic leukemia: A complementary study

The timing of cyclic cytotoxic chemotherapy can worsen neutropenia and neutrophilia

“…To assess whether resonance was indeed clinically significant, we leveraged a study of 286 Caucasian children diagnosed with ALL at the Sainte‐Justine University Health Center (Montreal, Canada). In these patients, variants in the DARC , GSDM and CXCL2 loci were previously identified as predictive for neutropenic complications during treatment with the Dana‐Farber Cancer Institute (DFCI) ALL Consortium protocols DFCI 87–01, 91–01, 95–01, or 00–01 10,11,32 . Detailed descriptions of these DFCI protocols are provided elsewhere 33–36 .…”

“…Detailed descriptions of these DFCI protocols are provided elsewhere 33–36 . Neutrophil counts were measured at 3‐week intervals prior to the next administration of chemotherapy, as previously described 10,11,32 . Using visual predictive check and Lomb–Scargle periodogram analysis, 37,38 we analysed these neutrophil data to check for significant oscillations in neutrophil counts over the treatment period of each patient.…”

“…Treatment strategies and schedules vary as a function of risk stratification and integrate a variety of chemotherapeutic and steroidal agents 3,9 . Neutropenia is a frequent side effect in childhood ALL; a recent retrospective analysis of 266 patients identified 74.7% of neutropenic episodes occurring during the induction phase of treatment 10–12 . On an individual basis, the optimal timing of periodic chemotherapy administration with or without adjuvant G‐CSF support is difficult to assess and is variable from person‐to‐person.…”

“…3,9 Neutropenia is a frequent side effect in childhood ALL; a recent retrospective analysis of 266 patients identified 74.7% of neutropenic episodes occurring during the induction phase of treatment. [10][11][12] On an individual basis, the optimal timing of periodic chemotherapy administration with or without adjuvant G-CSF support is difficult to assess and is variable from personto-person. The optimization of cytotoxic chemotherapy treatment with or without prophylactic or supportive G-CSF is therefore a question of intense research in both mathematical biology and the pharmaceutical sciences.…”

Characterizing chemotherapy-induced neutropenia and monocytopenia through mathematical modelling

“…Chemotherapyinduced neutropenia and ensuing infections are a common side effect of cytotoxic chemotherapy (Brooks et al, 2012;Craig et al, 2015;Friberg et al, 2002;Glisovic et al, 2018), necessitating dose size reductions or complete therapy cessation. These therapy modifications leave the patient particularly vulnerable to infection, a major cause of treatment-related mortality even in malignancies with high survival rates (Gatineau-Sailliant et al, 2019;Glisovic et al, 2018). Thus, there is intense interest in dampening the adverse hematological events associated with cytotoxic chemotherapy, through the design of less toxic chemotherapy combinations or the introduction of prophylactic agents.…”