CD34+ cells mobilized by cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) are functionally different from CD34+ cells mobilized by G-CSF

Abstract

Summary:Mobilized peripheral blood progenitor cells (PBPC) are increasingly used as an alternative to bone marrow for autografting procedures. Currently, cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) or G-CSF alone are the most commonly used PBPC mobilization schedules. In an attempt to investigate whether the use of these two mobilization regimens could result in the collection of functionally different CD34 ؉ cells, we analyzed nucleated cells (NC), CD34 ؉ cells, committed progenitor cells and long-term culture initiating-cells (LTC-IC) in 52 leukaphereses from 26 patients with lymphoid malignancies, mobilized either by CY+G-CSF (n ‫؍‬ 16) or G-CSF alone (n ‫؍‬ 10). Thirty-four aphereses from the CY+G-CSF group and 18 aphereses from the G-CSF group were investigated. According to the study design, leukaphereses were carried out until an average number of 7 ؋ 10 6 CD34 ؉ cells/kg body weight were collected. The mean (؎ s.e.m.) numbers of CD34 ؉ cells mobilized per apheresis by CY+G-CSF and G-CSF were not significantly different (2.76 ؎ 0.6 ؋ 10 8 vs 2.53 ؎ 0.4 ؋ 10 8 , P р 0.7). This resulted from a mean number of NC that was significantly lower in the CY+G-CSF products than in the G-CSF products (12.4 ؎ 1.7 ؋ 10 9 vs 32 ؎ 5.4 ؋ 10 9 , P р 0.0001) and a mean incidence of CD34 ؉ cells that was significantly higher in the CY؉G-CSF products than in the G-CSF products (2.9 ؎ 0.6% vs 0.9 ؎ 0.2%, P р 0.0018). The mean (؎ s.e.m.) number of CFU-GM collected per apheresis was significantly higher in the CY+G-CSF group than in the G-CSF group (37 ؎ 7 ؋ 10 6 vs 14 ؎ 2 ؋ 10 6 , P р 0.03). Interestingly, CY+G-CSF-mobilized CD34 ؉ cells had a significantly higher plating efficiency than G-CSF-mobilized CD34 ϩ cells (25.5 ؎ 2.9% vs 10.8 ؎ 1.9%, P р 0.0006). In addition, the mean number of LTC-IC was significantly higher in the CY+G-CSF products than in the G-CSF products (6.3 ؎ 1 ؋ 10 6 vs 3.3 ؎ 0.3 ؋ 10 6 , P р 0.05). In conclusion, our data provide evidence that CY؉G-CSF and G-CSF induce the mobilization of CD34 ؉ cells with

G-CSF Alone vs cyclophosphamide plus G-CSF in PBPC mobilization of patients with lymphoma: results depend on degree of previous pretreatment

“…Median time to reach a platelet count420 Â 10 9 /l was 12.2 days (range [10][11][12][13][14] in the 'G-CSF alone' mobilized group and 14.5 (range 11-23) days in the 'cyclophosphamide plus G-CSF' mobilized group (log-rank test: P-value ¼ 0.33).…”

“…In fact, in two studies, the amount of CD34+ cells harvested after these two regimens was similar, 12,13 while other authors found a higher mobilizing capacity for the association 'cyclophosphamide plus G-CSF'. [14][15][16] Furthermore, when studied as second line mobilization therapy in patient failing a previous mobilization scheme, 'G-CSF alone' and 'cyclophosphamide plus G-CSF' have been considered of equivalent efficacy.…”

A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone

“…[6][7][8][9][10] Some studies have shown a higher yield of CD34 þ cells following chemotherapy and growth factors than growth factors alone. 2,6 Although increasing the cyclophosphamide dose in combination with growth factor produces increased numbers of CD34 þ cells, this is associated with increased toxicity and morbidity.…”

“…6 Some studies have demonstrated the yield of CD34 þ cells to be superior to in-patients who have been treated with chemotherapy and growth factors rather than growth factor alone. 6,9,10 There has been only one previous randomised study comparing cyclophosphamide and G-CSF with G-CSF alone. 1 In this trial, we investigated the yield of CD34 þ cells following intermediate dose of cyclophosphamide followed by lenograstim (Cyclo-G-CSF group) vs lenograstim alone at 10 mg/kg/day (G-CSF group).…”

“…[6][7][8][9][10] Growth factor alone is used in dosages ranging from 3 to 32 mg/kg/ day. 6,11,12 The dose-response curve flattens at about 10 mg/ kg/day and this is the most commonly used and the recommended dose.…”