Da Silva et al1 conclude that remobilisation with a combination of Filgrastim and Ancestim (recombinant human stem cell factor, AMGEN) does not allow for the collection of an adequate dose of blood progenitor cells (BPC) in patients who failed an earlier BPC mobilisation attempt. However, their data show that four of the 20 patients actually had
3
106 CD34+ cells/kg collected on the study. Most transplanters would feel comfortable with proceeding to autologous PBPC transplant with this dose of cells. It therefore appears that their strategy is successful in 20% of patients, and this is a worthwhile result in a group of patients who are by definition difficult to mobilise.
In 1999/2000, a multicentric, phase I/II study (see Appendix A for 'participating centres') investigated the possibility of remobilising patients with haematological malignancies, by adding Ancestim 20
g/kg/day to the mobilisation regimen they had previously failed. Patients were eligible if they failed to mobilise >10 CD34+ cells/
l into the blood, or had a total CD34+ cell yield of 0.3–1
106/kg at the previous mobilisation attempt. In all, 32 patients with myeloma, Hodgkin's disease, and non-Hodgkin's lymphoma were enrolled, of which 12 had failed Filgrastim-only mobilisation, while 20 failed to mobilise following a combination of chemotherapy and Filgrastim. Remobilisation took place at a median of 60 days (range 7–173 days) after the initial attempt. One patient was withdrawn due to a serious adverse event.
Three of the 12 patients who had failed mobilisation with Filgrastim 10
g/kg/day alone had more than 2.5
106 CD34+ cells/kg collected when Ancestim was added to the mobilisation regimen. This required two leukaphereses in each. In the chemotherapy+Filgrastim+Ancestim group, 4/19 patients mobilised
2.5
106 CD34+ cells/kg, with the median of three (range, 2–4) leukaphereses. Overall, using the 2.5
106/kg CD34+ cell cutoff, 7/31 (22.5%) 'poor mobilisers' managed a less than optimal, but sufficient yield of CD34+ cells. In practice, if autologous transplant is considered to be potentially beneficial for the patient, having 2.5–3
106 CD34+ cells/kg would not deter the clinicians from proceeding.
To et al,2 in a study similarly designed to ours, found that 45–54% of poor mobilisers had a satisfactory CD34+ cell yield, which they defined as >2
106/kg, when remobilised with addition of Ancestim.
Numerous factors may affect the capacity for BPC mobilisation, not least patient selection and previous treatment. In addition, the interval between the two mobilisation attempts in our study was longer by approximately 1 month compared to Da Silva et al, possibly allowing more complete haemopoietic regeneration in some patients. While fiddling with the cutoff levels may change the response rates to a certain extent, we believe that the addition of Ancestim to Filgrastim
chemotherapy does enable adequate collection of BPC in a sizeable minority of patients who are considered to be 'poor mobilisers', with a potentially significant effect on their management.
References
| 1. | Da Silva MG, Pimentel P & Carvalhais A et al.. Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilisation in patients with a prior insufficient PBPC collection. Bone Marrow Transplant 2004; 34: 683−691. | Article | PubMed | ChemPort | |
| 2. | To LB, Bashford J & Durrant S et al.. Successful mobilisation of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilisation with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim. Bone Marrow Transplant 2003; 31: 371−378. | Article | PubMed | ChemPort | |
Appendices
Appendix A
Participating centers
King's College Hospital, London (Professor GJ Mufti, Dr A Mijovic), Royal Marsden Hospital, London (Professor R Powles), Royal Free Hospital, London (Dr M Potter), Nottingham City Hospital (Professor N Russell), St James'Hospital, Dublin (Dr P Browne), St Vincent's Hospital, Dublin (Dr J Crown), Belfast City Hospital (Dr TCM Morris) and Royal Liverpool University Hospitals (Dr RE Clark).
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