Impaired Stem Cell Collection by Consecutive Courses of High-Dose Mobilizing Chemotherapy Using Cyclophosphamide, Etoposide, and G-CSF

Abstract

Tandem cycles of myeloablative chemotherapy can increase dose intensity and total dose of chemotherapy, but sufficient numbers of progenitor cells must be collected to ensure hematologic recovery after each treatment. This study was undertaken to determine if two courses of mobilizing chemotherapy given 4 weeks apart using cyclophosphamide 4000 mg/m2 and etoposide 400 mg/m2, combined with G-CSF 5-10 mg/kg on days 3-16 could each provide sufficient numbers of peripheral blood progenitor cells to support tandem cycles of myeloablative chemotherapy in 20 patients with stage IV breast cancer. Leukapheresis of blood with WBC > 1000/mm3 was performed daily for up to five collections (days 12-16), and mononuclear cells, CFU-GM, and CD34+ cells were compared between the first and second collections. The second course of mobilizing treatment resulted in similar numbers of mononuclear cells collected but far fewer CFU-GM and CD34+ progenitor cells. This prevented using the second collection of progenitor cells as the sole source for the second transplant. The data suggest that a second course of cyclophosphamide, etoposide, and G-CSF given 4 weeks after the first leads to progenitor cell depletion, and efforts to increase the yield of blood-derived progenitors should focus on the initial mobilizing procedure.

High-dose ara-C with autologous peripheral blood progenitor cell support induces a marked progenitor cell mobilization: an indication for patients at risk for low mobilization

“…[55][56][57] However, previous reports have shown that repeated chemotherapy courses, especially if given at short intervals, may severely hamper mobilization. 34 In particular, low mobilization has been observed after HD VP16 when delivered shortly after HD CY. 35 PBPC collections are only feasible if the mobilizing course is delivered after an adequate chemotherapy-free interval from a previous cytotoxic treatment.…”

“…[31][32][33] However, they may severely hamper mobilization, especially if given at short intervals. 34,35 This paper describes the evaluation of an innovative mobilizing procedure consisting of the administration of HD cyclophosphamide (CY) followed by HD ara-C, two drugs with a high mobilizing activity. Post-CY harvested PBPC were reinfused following HD ara-C to reduce hematological toxicity.…”

Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation

“…33 However, using chemotherapy appears to impair the future mobilization of adequate numbers of CD34 ϩ cells. 12,34 We have provided evidence from a randomized study that G-CSF alone is adequate for progenitor cell mobilization. This was true, even in heavily pretreated patients with relapsed lymphoma.…”

Post-chemotherapy and cytokine pretreated marrow stromal cell layers suppress hematopoiesis from normal donor CD34+ cells

“…[6][7][8] Similarly, low yields of CD34 + cells and hematopoietic progenitor/stem cells during peripheral blood mobilization regimens correlated with the type and timing of prior chemotherapy. [9][10][11] The causes for these deficiencies have not been ascertained.…”