How many myeloid post-progenitor cells have to be transplanted to completely abrogate neutropenia after peripheral blood progenitor cell transplantation? Results of a computer simulation

Although hematopoietic recovery following high-dose chemotherapy (HD-CT) an d peripheral blood progenitor cell (PBPC) transplantation is rapid, there i s still a 5- to 7-day period of severe neutropenia which, theoretically, mi ght be abrogated by an additional transplantation of more differentiated my eloid post-progenitor cells (MPPC). However, both the number of MPPC requir ed to abrogate neutropenia as well as the optimum scheduling of MPPC infusi ons are currently unknown. Therefore, these questions were addressed by app lying a computer model of human granulopoiesis. First, model calculations s imulating varying levels of chemotherapy dose intensity were performed and compared with typical clinical neutrophil recovery curves. Using this appro ach, the data for HD-CT without PBPC transplantation could be reproduced by assuming a reduction of stem cells, committed granulopoietic progenitors a nd proliferating precursors to about 0.001% of normal. PBPC-supported HD-CT was reproduced by increasing the starting values to at least 0.1%, which c orresponded to about I to 2 X 10(5)/kg transplanted CFU-GM. Interestingly, reproduction of PBPC-supported HD-CT data could be observed for a wide rang e of starting values (0.1%-10% of normal), thus confirming the clinical obs ervation that hematopoietic recovery after PBPCT cannot be improved by incr easing the dose of transplanted cells over a certain threshold. Using the s ame simulation model, we then studied the effects of an additional MPPC tra nsplantation. The results showed, that at least 5.7 X 10(8) MPPC/kg have to be provided in addition to the normal PBPC graft to avoid neutropenia <100 /mu L, and that MPPC are best transplanted on days 0 and 6 after HD-CT, Ass uming a 100- to 120-fold cellular es-vivo expansion rate and MPPC represent ing about 70% of total expanded cells, 5.7 X 10(8) MPPC/kg could be generat ed starting from 1 to 2 leukapheresis preparations with about 7 to 8 x 10(6 ) CD34(+) PBPC/kg, Considering furthermore, that only a fraction of ex-vivo generated cells will seed and effectively produce neutrophils in-vivo, the required number of MPPC is most likely even higher and, therefore, might h e difficult to be achieved clinically, However, the validity of the model r esults remains to be proven in appropriate clinical studies. (C) 1999 Inter national Society for Experimental Hematology. Published by Elsevier Science Inc.