Mobilization of peripheral blood stem cells following myelosuppressive chemotherapy: a randomized comparison of filgrastim, sargramostim, or sequential sargramostim and filgrastim

Myelosuppressive chemotherapy is frequently used for mobilization of autolo gous CD34(+) progenitor cells into the peripheral blood for subsequent coll ection and support of high-dose chemotherapy. The administration of myelosu ppressive chemotherapy is typically followed by a myeloid growth factor and is associated with variable CD34 cell yields and morbidity. The two most c ommonly used myeloid growth factors for facilitation of CD34 cell harvests are granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophag e colony-stimulating factor (GM-CSF). We performed a randomized phase III c linical trial comparing G-CSF, GMCSF, and sequential administration of GM-C SF and G-CSF following administration of myelosuppressive chemotherapy. We evaluated CD34 yields, morbidity, and cost-effectiveness of the three cytok ine schedules. One hundred and fifty-six patients with multiple myeloma, br east cancer, or lymphoma received cyclophosphamide with either paclitaxel o r etoposide and were randomized to receive G-CSF 6 mug/kg/day s.c., GMCSF 2 50 mug/m(2)/day s.c., or GM-CSF for 6 days followed by G-CSF until completi on of the stem cell harvest. Compared with patients who received GM-CSF, pa tients who received G-CSF had faster recovery of absolute neutrophil count to 0.5 x 10(9) per liter (median of 11 vs 14 days, P = 0.0001) with fewer p atients requiring red blood cell transfusions (P = 0.008); fewer patients w ith fever (18% vs 52%, P = 0.001); fewer hospital admissions (20% vs 42%, P = 0.13); and less intravenous antibiotic therapy (24% vs 59%, P = 0.001). Patients who received G-CSF also yielded more CD34 cells (median 7.1 vs 2.0 x 10(6) kg per apheresis, P = 0.0001) and a higher percentage achieved 2.5 x 10(6) CD34 cells per kilogram (94% vs 78%, P = 0.21) and 5 x 10(6) CD34 cells per kilogram (88% vs 53%, P = 0.01) or more CD34 cells per kilogram w ith fewer aphereses (median 2 vs 3, P = 0.002) and fewer days of growth fac tor treatment (median 12 vs 14, P = 0.0001). There were no significant diff erences in outcomes between groups receiving G-CSF alone and the sequential regimen. After high-dose chemotherapy, patients who had peripheral blood s tem cells mobilized with G-CSF or the sequential regimen received higher nu mbers of CD34 cells and had faster platelet recovery with fewer patients re quiring platelet transfusions than patients receiving peripheral blood stem cells mobilized by GMCSF. In summary, G-CSF alone is superior to GM-CSF al one for the mobilization of CD34(+) cells and reduction of toxicities follo wing myelosuppressive chemotherapy. An economic analysis evaluating the cos t-effectiveness of these three effective schedules is ongoing at the time o f this writing.