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.

G-CSF administration following peripheral blood progenitor cell (PBPC) autograft in lymphoid malignancies: evidence for clinical benefits and reduction of treatment costs

“…16,19 Thus, any further acceleration induced by growth factor adminisClinical value and costs of G-CSF administration following autograft with mobilized peripheral blood protration may be difficult to assess. In addition, the speed of BM recovery may be variably influenced by other congenitor cells (PBPC) were evaluated in two sequential groups of 20 patients each, treated for lymphoid neofounding factors, such as quantity of progenitor cells reinfused, type of conditioning regimen and previous treatplasms in the period February 1993 to January 1996.…”

“…30,32,33 loablative regimens. [16][17][18][19]32,33 A direct correlation between the number of reinfused progenitors and speed of hematolAlternatively, the less pronounced thrombocytopenia might be correlated with better clinical conditions, resulting from ogic recovery is well known and values ranging from 2 to 5 × 10 6 CD34 + cells/kg have been proposed as the minia shorter neutropenic duration; this could favor platelet survival with improved efficacy of platelet transfusions and mum PBPC dose required to guarantee rapid and stable engraftment. 21,[33][34][35][36] In our HDS programs, a dose as high overall milder thrombocytopenia.…”

Quality of IL-3 and G-CSF-mobilized peripheral blood stem cells in patients with early chronic phase CML

“…Unseparated MNC as well as culture cells were grown in a standard methylcellulose assay as described previously. 16 Cytogenetic analysis of bone marrow Cytogenetic analysis was performed only before mobilization therapy. MNC from bone marrow aspirates were isolated by density gradient centrifugation over Ficoll-Hypaque (Pharmacia).…”

Ifosfamide in combination with paclitaxel or doxorubicin: regimens which effectively mobilize peripheral blood progenitor cells while demonstrating anti-tumor activity in patients with metastatic breast cancer

“…Although ifosfamide has previously been incorporated into chemotherapy regimens to mobilize PBPCs, [8][9][10][11][12][13][14] these studies have not been restricted to patients with breast cancer, [8][9][10][11]14 and those with breast cancer have generally been minimally pre-treated and not had metastatic or relapsed disease. 12,13 The choice of the most appropriate mobilization regimen for patients with previously treated disease is further limited by prior cyclophosphamide and/or anthracycline exposure.…”

“…Firstly, ifosfamide can be incorporated into chemotherapy regimens to mobilize PBPCs. [8][9][10][11][12][13][14] Secondly, ifosfamide has some potential 428 advantages over cyclophosphamide. Pre-clinical studies have demonstrated that the unique structural properties of ifosfamide may have a beneficial anti-tumor activity; ifosfamide is an analogue of cyclophosphamide with translocation of a chlorethyl group which provides a more effective DNA cross-linking distance between two independent functional alkylating moieties.…”