Influence of mobilized peripheral blood cells on the hematopoietic recovery by autologous marrow and recombinant human granulocyte- macrophage colony-stimulating factor after high-dose cyclophosphamide, etoposide, and cisplatin

Abstract

Peripheral blood cells (PBC) can hasten hematopoietic recovery after high-dose chemotherapy. To determine if PBC apheresed after mobilization further enhance hematopoietic recovery over that achieved with autologous bone marrow (ABM) and recombinant human granulocyte- macrophage colony-stimulating factor (rhGM-CSF), 14 patients with metastatic solid tumors were supported by ABM and rhGM-CSF during the first course of high doses of cyclophosphamide, etoposide, and cisplatin (CVP) and 11 of these 14 patients by mobilized PBC with ABM and rhGM-CSF during the second CVP. Each patient served as his or her own control. Identical doses of CVP were administered in both courses: cyclophosphamide 5.25 g/m2, etoposide 1,200 mg/m2, and cisplatin 165 to 180 mg/m2. PBC were collected on day 10 after mobilization with cyclophosphamide (3 g/m2) intravenously (IV) on day 1, doxorubicin (50 mg/m2) as a continuous IV infusion over 48 hours starting day 2, and rhGM-CSF as a daily 4-hour IV infusion starting day 4 at 0.6 mg/m2 for 14 days. Comparing recovery in the 11 patients to receive two cycles of therapy, the median days to an absolute neutrophil count of 0.1 x 10(9)/L and 0.5 x 10(9)/L were not statistically significant between the two courses; neither was there a difference in the incidence of fever and bacteremia. The median number of days to platelet count of 0.02 x 10(12)/L unmaintained by platelet transfusion was 20 from marrow infusion for course 1 and 16 for course 2 (P = .059). The median number of days to a platelet count of 0.05 x 10(12)/L was significantly shortened: 24 and 19 days for courses 1 and 2, respectively (P = .045). Patients who received PBC required fewer number of platelet transfusions. Extramedullary toxicities were not different between the groups. Our finding of enhanced early recovery of platelets and reduced platelet transfusion requirement is in concordance with other studies.

Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating-factor support for dose-intensive cyclophosphamide, etoposide, and cisplatin

“…Reinfusion of autologous bone marrow cells without hematopoietic growth factors did not alter this pattern of recovery. When a combination of bone marrow, peripheral blood stem cells, and GM-CSF was administered after a second cycle of DICEP, recovery of platelets was accelerated by 4 days [33]. There are no data regarding use of autologous hematopoietic progenitor cell support following a third cycle of DICEP.…”

“…It is also possible that GM-CSF may differentiate uncommitted progenitors into committed myeloid precursors thereby "stealing" the progenitors and compromising the recovery of platelet counts. Infusion of a large number of progenitors may overcome the problem [33]. However, the enhancement of recovery may not worth the risk of possible tumor cell reinfusion.…”

G‐ and GM‐CSF in oncology and oncological haematology

“…In addition, chemotherapy-related toxicity may be reduced by the use of myeloid growth factors. Transplantation of peripheral stem cells mobilised by chemotherapy + Gor GM-CSF has given excellent results in terms of fast haematopoietic recovery (225,228,229).…”

Standard dose cisplatin with rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer

“…of solid and hematologic tumors. Large numbers of peripheral blood stem cell (PBSC) can be mobilized and collected following administration of growth factors, chemotherapy, or both, and reinfused with or without autologous marrow following high-dose chemotherapy and/or irradiation (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). High-dose cyclophosphamide (7 g m -2) or intermediate dose cyclophosphamide (3-4 g m -2) with or without growth factors are effective antitumor treatments which produce powerful PBSC mobilization (6ql).…”