Peripheral blood progenitor cells mobilized by chemotherapy plus granulocyte-colony stimulating factor accelerate both neutrophil and platelet recovery after high-dose VP16, ifosfamide and cisplatin.

Abstract

We report on the chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood progenitor cells (PBPCs) and their impact on haematopoietic recovery following high-dose chemotherapy. Twenty-four patients with advanced solid tumours or lymphomas received standard-dose chemotherapy with VP16, ifosfamide and cisplatin (VIP) followed by filgrastim (G-CSF; 5 micrograms/kg s.c. daily for 14 d) for the prevention of chemotherapy induced neutropenia and for the simultaneous mobilization of PBPCs. Maximal numbers of progenitors of different lineages were reached at day 11 (range 9-14) after VIP chemotherapy. A median of 0.415 x 10(9)/l CD34+ cells (range 0.11-1.98), 9000 CFU-GM/ml (range 2800-17,700), 3500 BFU-E/ml (range 400-10,800) and 200 CFU-GEMM/ml (range 0-4400) were recruited. One single apheresis yielded a median of 1.6 x 10(8) mononuclear cells/kg (range 0.2-5.4) or 5.4 x 10(6) CD34+ cells/kg body weight (range 0.2-24.2). Fourteen patients who showed at least a partial remission after two cycles of the standard-dose chemotherapy regimen were subjected to high-dose VIP chemotherapy (cumulative doses of 1500 mg/m2 VP16, 12 g/m2 ifosfamide and 150 mg/m2 cisplatin) with or without PBPC support. The first six patients were treated with growth factors only (IL-3/GM-CSF) and did not receive PBPCs, whereas the following eight patients were supported with PBPCs in addition to IL-3 and GM-CSF. Neutrophil recovery as well as platelet recovery were significantly faster in patients receiving PBPCs with a median of 6.5 d below 0.1 x 10(9) neutrophils/l and 3 d below 20 x 10(9) platelets/l as compared to 10.5 d and 8 d in control patients receiving growth factors only. The accelerated platelet recovery in patients supported with PBPCs might be explained--in the absence of detectable colony-forming units megakaryocyte--by the presence of glycoprotein IIb/IIIa+, non-proliferating endomitotic megakaryocytic precursor cells within G-CSF mobilized PBPCs. Our data demonstrate that chemotherapy plus G-CSF mobilized PBPCs accelerate both neutrophil and platelet recovery after high-dose VIP chemotherapy in patients with solid tumours or lymphomas.