Mathematical modeling of granulocyte reconstitution after high-dose chemotherapy with stem cell support: effect of post-transplant G-CSF treatment.

Cancer patients treated with high-dose chemotherapy and autotransplanted with peripheral blood progenitor cells most often reconstitute neutrophils (> 0.5 x 10(9)c/l) 8-16 days after the initiation of treatment. By means of a mathematical model of human granulopoiesis, the present work assesses the effect of administering granulocyte colony stimulating factor (G-CSF) post-transplant to reduce engraftment time, and also assesses the effect of delaying initiation of G-CSF treatment relative to a general schedule. Hematopoietic progenitor cells from 21 breast cancer patients were mobilized by chemotherapy followed by G-CSF injections. Purified CD34+ cells taken from the mobilized blood were infused 3 days after termination of chemotherapy. Patients were given subcutaneous injections of G-CSF post-transplant (5 microg/kg every 12 h). Neutrophil counts calculated from a mathematical model were compared with data from individual patients. These results were also compared with data and modeling results from a group of 19 lymphoma patients given no post-transplant G-CSF therapy. The observed engraftment times were associated with the number of CFU-GM cells in the reinfused blood graft and the administration of post-transplant G-CSF. The latter finding was most predominant in patients given < 5.0 x 10(5) CFU-GM/kg bw. These tendencies were well captured by the model. Interestingly, the model showed no major differences in time to engraft neutrophils if the initiation of G-CSF was postponed for up to 5 days after transplantation. Our findings indicate that the present mathematical model of neutrophil recovery following high-dose therapy correlates with clinical observations and can potentially be used to predict time to neutrophil recovery.