Randomized cross-over trial of progenitor-cell mobilization: High-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF

Purpose: patient response to hematopoietic progenitor-cell mobilizing regim ens seems to vary considerably, making comparison between regimens difficul t. To eliminate this inter-patient variability, we designed a cross-over tr ial and prospectively compared the number of progenitors mobilized inta blo od after granulocyte-macrophage colony-stimulating factor (GM-CSF) days 1 t o 12 plus granulocyte colony-stimulating factor (G-CSF) days 7 to 12 (regim en G) with the number of progenitors after cyclophosphamide plus G-CSF days 3 to 14 (regimen C) in the same patient. Patients and Methods: Twenty-nine patients were randomized ta receive eithe r regimen G or C first(G1 and C1, respectively) and underwent two leukapher eses. After a washout period, patients were then crossed over to the altern ate regimen [C2 and G2, respectively) and underwent two additional leukaphe reses. The hematopoietic progenitor-cell content of each collection was det ermined. In addition, toxicity and charges were tracked. Results: Regimen C (n = 50) resulted in mobilization of more CD34(+) cells (2.7-fold/kg/apheresis), erythroid burst-forming units(1.8-fold/kg/apheresi s), and colony-forming units-granulocyte-macrophage (2.2-fold/kg/apheresis) compared with regimen G given ta the same patients (n = 46;paired t test, P < .01 for all comparisons). Compared with regimen G, regimen C resulted i n better mobilization, whether it was given first (P = .025) or second (P = .02). The ability to achieve a target collection of greater than or equal to 2 x 10(6) CD34(+) cells/kg using two leukaphereses was 50% after G1 and 90% after C1. Three of the seven patients in whom mobilization was poor aft er G1 had greater than or equal to 2 x 10(6) CD34(+) cells/kg with two leuk aphereses after C2. In contrast, when regimen G was given second (G2), seve n out of 10 patients failed to achieve the target CD34(+) cell dose despite adequate collections after C1. Thirty percent of the patients (nine of 29) given regimen C were admitted to the hospital because of neutropenic fever for a median duration of 4 days (range, 2 to 10 days). The higher cost of regimen C was balanced by higher CD34(+) cell yield, resulting in equivalen t charges based on cost per CD34(+) cell collected. Conclusion: We report the first clinical trial that used a cross-over desig n showing that high-dose cyclophosphamide plus G-CSF results in mobilizatio n of more progenitors then GM-CSF plus G-CSF when tested in the same patien t regardless of sequence of administration, although the regimen is associa ted with greater morbidity. patients who fail to achieve adequate mobilizat ion after regimen G can be treated with regimen C as an effective salvage r egimen, whereas patients who fail regimen C are unlikely ta benefit from su bsequent treatment with regimen G. The cross-over design allowed detection of significant differences between regimens in a small cohort of patients a nd should be considered in design of future comparisons of mobilization reg imens. (C) 2000 by American Society of Clinical Oncology.