Cytoreduction of lymphoid malignancies and mobilization of blood hematopoietic progenitor cells with high doses of cyclophosphamide and etoposide plus filgrastim.
We evaluated the efficiency of high doses of cyclophosphamide (6 g/m2) and etoposide (2 g/m2) 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/m2 twice daily for 10 doses, etoposide 200 mg/m2 twice daily for 10 doses (continuous; n=57) or 2 g/m2 over 10 hours on day 5 of etoposide (bolus; n=22), and G-CSF 5 microg/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/microL neutrophils and >20000/microL 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>or=3 nonhematologic toxicity. Patients receiving bolus etoposide had significantly less grade>or=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.
Damon
Lloyd
L
University of California, San Francisco, San Francisco, California 94143-0324, USA. damonl@medicine.ucsf.edu
Rugo
Hope
H
Tolaney
Sara
S
Navarro
Willis
W
Martin
Thomas
T
Ries
Curt
C
Case
Delvyn
D
Ault
Kenneth
K
Linker
Charles
C
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D006085:Graft Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology / Q000401:mortality / Q000628:therapy; D019653:Myeloablative Agonists / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D011994:Recombinant Proteins; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D014182:Transplantation, Autologous; D047368:Tumor Burden / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D019653:Myeloablative Agonists; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D003520:Cyclophosphamide; D000069585:Filgrastim