Purpose: To examine the ability of carboplatin to mobilize peripheral-blood progenitor cells (PBPCs) and to examine the impact of infusing these cells on myelosuppression following multiple cycles of high-dose therapy. Fluctuations in circulating progenitor cell concentration following repeated cycles of this therapy were also measured.
Patients and methods: Eight patients received a total of 20 cycles of carboplatin 1,200 mg/m2 per course, granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 micrograms/kg/d, and PBPC reinfusion every 28 days. PBPC were collected following 1 week of GM-CSF and following the first and second cycles of chemotherapy. Hematologic toxicity was correlated with the number of progenitor cells reinfused per cycle. The concentration of PBPC per milliliter of blood was measured at study entry, following GM-CSF priming, and after each cycle of chemotherapy.
Results: We observed a strong inverse correlation between the number of PBPCs (CD34 and colony-forming unit granulocyte-macrophage [CFU-GM]), but not mononuclear cells (MNCs) reinfused and the days with neutropenia less than 500/microL and platelets less than 20,000/microL. Compared with baseline levels, the circulating PBPC concentration increased up to 27-fold following the first course of chemotherapy, but decreased toward, and eventually below, baseline following the second and third cycles of carboplatin.
Conclusion: PBPC reinfusion directly correlated with a reduction in myelosuppression following high-dose carboplatin chemotherapy. While high-dose carboplatin plus GM-CSF leads to a substantially greater mobilization of PBPC than GM-CSF alone, this effect is lost after multiple treatment cycles. These results emphasize the importance of early procurement and value of PBPC reinfusion in conjunction with multiple cycles of dose-intensive chemotherapy.