Mobilization of peripheral blood stem cells in myeloma with either pegfilgrastim or filgrastim following chemotherapy

Abstract

Quality and quantity of mobilized peripheral blood stem cells determine the safety of tandem autologous transplants in myeloma. Using the same mobilization chemotherapy with DT-PACE in two consecutive protocols, robustness of stem cell collection and rapidity of engraftment after transplantation were assessed. We employed either twice a day filgrastim versus two doses of pegfilgrastim. Advantages of pegfilgrastim were: (i) a higher percentage of patients collected 15x10 6 /kg in the first three days (p<0.001); (ii) the median number of CD34 cells/kg collected on day 1 was higher (p=0.004 ); (iii) the median number of growth factor injections was 2 versus 26 (p<0.0001); (iv) post-transplantation neutrophil recovery was faster after first and second transplant (p<0.001) and (v) platelet recovery was faster after first transplant (when less stem cells were infused) (p=0.01). Pegfilgrastim may be considered the standard of care for stem cell mobilization.

Pegfilgrastim for PBSC mobilization and autologous haematopoietic SCT

“…An additional advantage compared with the use of conventional G-CSF is the faster neutrophil recovery after pegfilgrastim, which may be associated with a reduced risk of infection-related complications during neutropenia. Another benefit of cytotoxic stem cell mobilization with pegfilgrastim is the reduction of the number of injections required from 11 (median; range: 8-15) to 1 injection in our study, and from a median number of 26 to 2 injections in the study of Tricot et al, 23 which increases patient comfort and convenience.…”

“…On the other hand, it has been shown that the pegylation of G-CSF not only enhances serum half-life, and thus receptor occupancy, but also alters the cellular trafficking of G-CSF to enhance G-CSF receptor stimulation at a cellular level. 38 The first clinical evidence for this phenomenon has recently been presented by Tricot et al 23 In their double transplant study on 237 myeloma patients in two consecutive protocols at the University of Arkansas, they found a significantly faster recovery of neutrophils and platelets after transplantation of pegfilgrastim-mobilized haematopoietic stem cell grafts in comparison with conventional G-CSF. The advantage of pegfilgrastim-mobilized cells disappeared during the second transplant when the number of reinfused CD34 þ cells was increased from about 4 million to more than 6 million/kg patient weight.…”

“…For this reason, it is possible that the mobilization could be improved if the level of G-CSF was increased by means of a booster injection of either pegfilgrastim or conventional G-CSF during the early phase of haematopoietic recovery. This issue has been addressed by Tricot et al 23 who routinely used two 6 mg doses of pegfilgrastim, on day þ 6 and on day þ 13, respectively, after DT-PACE (dexamethasone, thalidomide, cisplatin, doxorubicine, cyclophosphamide and etoposide) in 140 patients with multiple myeloma. With this dose and schedule, they found a superior mobilization of CD34 þ cells in comparison with 5 mg/kg filgrastim given twice daily from day þ 6 after DT-PACE.…”

Pegfilgrastim compared with filgrastim for cytokine-alone mobilization of autologous haematopoietic stem and progenitor cells

“…Another group reported superior efficacy to filgrastim plus chemotherapy mobilization when two doses of pegfilgrastim were administered, at day þ 6 and day þ 13 post aggressive salvage chemotherapy in multiple myeloma. 22 In aggressive lymphoma post ESHAP (etoposide, methylprednisolone, cytarabine and cisplatin) chemotherapy pegfilgrastim 6 mg has demonstrated similar mobilization efficacy to a control group mobilized with filgrastim post ESHAP. 23 The adverse event profile of pegfilgrastim mobilization is very similar to filgrastim mobilization, including bone pain, skin reaction and rare reports of splenic rupture.…”

Optimal mobilization method and CD34+ dose calculation for autologous PBSC transplant in myeloma patients: two important unresolved questions

“…On the other hand, some groups have observed best mobilization results with pegylated G-CSF (pegfilgrastim) compared with standard G-CSF not pegylated. 18,19 Recently, this method has been evaluated by Tricot et al 19 This study showed that PBSC post-chemotherapy is feasible and similarly effective with pegfilgrastim and filgrastim, with the advantages of greater ease and cost-effectiveness with pegfilgrastim. For these authors, pegfilgrastim may become the standard growth factor to be used for stem cell mobilization with or without chemotherapy.…”