Peripheral Blood Stem Cell Mobilization with Cyclophosphamide in Combination with G-CSF, GM-CSF, or Sequential GM-CSF/G-CSF in Non-Hodgkin's Lymphoma Patients: A Randomized Prospective Study

Abstract

We designed a randomized, prospective three-arm mobilization study to determine the kinetics of peripheral blood stem cell (PBSC) mobilization in 60 non-Hodgkin's lymphoma (NHL) patients primed with cyclophosphamide (CTX) in combination with granulocyte colony-stimulating factor (G-CSF) (arm A), granulocyte-macrophage (GM)-CSF (arm B) or GM-CSF/G-CSF (arm C). We also compared mobilization and transplant-related toxicities, pre- and post-transplant support and the probability of survival among the three arms. To date, 35 patients have been enrolled in the study; 13 patients have been enrolled in arm A, 10 patients in arm B, and 13 patients in arm C. Successful collection of the target of > or = 2 X 10(6) CD34+ cells/kg in one to four apheresis collections was 10/13, 6/10, and 7/12 in arms A, B, and C, respectively. The differences between arms were not statistically significant. The median time to achieve the target CD34+ cells in patients who successfully mobilized the target CD34+ cells was 3 days, 2 days, and 1 day, in patients in arms A, B, and C, respectively. The time for neutrophil engraftment was 11, 10, and 10 days in arms A, B, and C, respectively. The time for platelet engraftment was 11 days for patients in all arms of the study. Most importantly, no significant differences were observed among the three arms in the duration of neutropenic fever, the extent of mucositis, diarrhea, and nausea/vomiting, or in the number of units of platelets or red cells transfused after transplantation. Risk factors associated with poor mobilization were > or = 3 regimens of chemotherapy prior to mobilization, older age, and disease histology (follicular versus diffuse). Therefore, we conclude that the type of growth factor used for mobilization did not play a major role in the outcome of mobilization and recommend mobilizing NHL patients before they receive multiple regimens of chemotherapy.

Improving stem cell mobilization strategies: future directions

“…96 Mobilization regimens combining GM-CSF with G-CSF have consisted of sequential or concurrent administration of these agents at a range of doses (G-CSF, 5-10 mg/kg; GM-CSF, 5 mg/kg-250 mg/m 2 ), with or without chemotherapeutic agents. 35,71,97,98 These combination regimens have not been shown to have substantial benefits over regimens that use G-CSF alone; therefore, GM-CSF and G-CSF are not commonly administered together for primary mobilization. However, the combination of G-CSF and GM-CSF is used as a salvage mobilization regimen when mobilization with G-CSF alone has been unsuccessful.…”

The whys and hows of hematopoietic progenitor and stem cell mobilization

“…25 In donors with lymphoma, low numbers of circulating natural killer (NK) CD3 À 16 + 56 + cells prior to administration of mobilizing therapies have predicted poor mobilization, 72 as have low platelet counts on the first day of autologous blood stem/progenitor cell collection. 73 Older age was associated with poor autologous mobilization in some patient groups, 30,74,75 but not in others. 74,76 Even though some donors with predictors of poor mobilization respond quite well to mobilizing therapies, 77 poorly mobilizing autologous donors are assumed to have sustained an injury to the hematopoietic stem cell system that is responsible for the poor effect (see Table 4).…”

“…29 In contrast, for patients with non-Hodgkin's lymphoma (NHL), GM-CSF followed by G-CSF permitted more efficient collection of a target number of CD34+ cells than did GM-CSF, while G-CSF was the least efficient of the three cytokine strategies. 30 However, cyclophosphamide plus either G-CSF, GM-CSF or GM-CSF plus interleukin 3 (IL-3) mobilized equally well in another trial. 31 Studies including erythropoietin (EPO) have found that it did 32 and that it did not 33 increase mobilization when added to G-CSF after chemotherapy .…”

“…63,64,69 Of these patients, 16-33% were unable to mobilize enough collectable stem/progenitor cells for transplantation. 63,69 Factors predicting for a higher likelihood of poor mobilization include increasing numbers of cycles of prior antitumor chemotherapy administration, 70 prior radiation therapy, 70,71 follicular rather than diffuse NHL as the underlying disease, 30 and the presence of overt marrow metastases. 25 In donors with lymphoma, low numbers of circulating natural killer (NK) CD3 À 16 + 56 + cells prior to administration of mobilizing therapies have predicted poor mobilization, 72 as have low platelet counts on the first day of autologous blood stem/progenitor cell collection.…”

Low doses of GM-CSF (molgramostim) and G-CSF (filgrastim) after cyclophosphamide (4 g/m2) enhance the peripheral blood progenitor cell harvest: results of two randomized studies including 120 patients

“…25 Several non-randomized or randomized clinical trials have been performed, showing a little or no benefit for sequential administration of standard doses (5-10 mg/kg/d) of GM-CSF and G-CSF. [26][27][28][29][30][31][32][33][34][35][36][37] Neverthelesss, the use of these HGFs was not well explored and particularly the minimal efficient dose for their concomitant administration, following high dose cyclophosphamide (CY). We report here two randomized studies comparing G-CSF to the association of G-CSF and GM-CSF.…”