Cytoreduction of Lymphoid Malignancies and Mobilization of Blood Hematopoietic Progenitor Cells with High Doses of Cyclophosphamide and Etoposide Plus Filgrastim

Abstract

We evaluated the efficiency of high doses of cyclophosphamide (6 g/m 2) and etoposide (2 g/m 2) plus filgrastim (granulocyte colony-stimulating factor; G-CSF) to mobilize autologous hematopoietic progenitor cells in patients with non-Hodgkin lymphoma, multiple myeloma, and Waldenström macroglobulinemia. We also evaluated the safety of this regimen and the engraftment kinetics after myeloablative chemotherapy. Seventy-nine patients with high-risk or relapsed/primary refractory non-Hodgkin lymphoma, multiple myeloma, or Waldenström macroglobulinemia were treated. The mobilizing regimen was as follows: cyclophosphamide 600 mg/m 2 twice daily for 10 doses, etoposide 200 mg/m 2 twice daily for 10 doses (continuous; n = 57) or 2 g/m 2 over 10 hours on day 5 of etoposide (bolus; n = 22), and G-CSF 5 μg/kg/d beginning day 14. Fifty-nine percent of patients achieved the primary end point (a CD34 cell dose of 5 million per kilogram with a single leukapheresis). More bolus etoposide patients achieved the primary end point (86%) compared with continuous etoposide patients (47%; P < .0001). The CD34 cell dose collected was greater in bolus etoposide patients (44 million per kilogram) than in continuous etoposide patients (10.9 million per kilogram; P < .0001). Patients took 3 weeks to recover >500/μL neutrophils and >20000/μL platelets after cyclophosphamide and etoposide. The overall response rate was 69% for non-Hodgkin lymphoma patients and 71% for multiple myeloma/Waldenström macroglobulinemia patients. The treatment-related mortality was 2.5%. Sixteen percent of surviving patients experienced grade ≥3 nonhematologic toxicity. Patients receiving bolus etoposide had significantly less grade ≥2 oral mucositis, less use of total parenteral nutrition, and less need for red blood cell and platelet transfusions. Sixty-four patients (81%) underwent autologous hematopoietic progenitor cell transplantation, with prompt engraftment. Four patients (5%) did not undergo autologous hematopoietic progenitor cell transplantation because of toxicity from high-dose cyclophosphamide and etoposide. We conclude that high doses of cyclophosphamide and etoposide combined with G-CSF are an efficient and safe mobilizing regimen for the collection of hematopoietic progenitor cells during aggressive cytoreduction of tumor burden in patients with lymphoid malignancies.