Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.

The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy.

Abnormal heart rate pattern in fetal anaemia secondary to transient abnormal myelopoeisis in a fetus without trisomy 21: A case report.

Decreased fetal movements (DFM) are a non-specific and common symptom in the third trimester of pregnancy that hold an association with fetal compromise. A 28-year-old woman at 31 weeks and 3 days of gestation presented with DFM and was found to have a pathological fetal heart rate trace. Following emergency Caesarean section the fetus was diagnosed with transient abnormal myelopoeisis (TAM). Timely treatment was initiated and the neonatal outcome was good. Transient myeloproliferative disorders are almost uniquely found in infants with trisomy 21 (T21). This is the first case report of TAM in the absence of T21 wherein the diagnostic process was commenced antenatally due to non-reassuring fetal status and highlights the importance of antenatal heart rate abnormalities.