Stem cell factor and high-dose twice daily filgrastim is an effective strategy for peripheral blood stem cell mobilization in patients with indolent lymphoproliferative disorders previously treated with fludarabine: results of a Phase II study with an historical comparator

Abstract

Fludarabine exposure leads to impaired peripheral blood stem cell (PBSC) mobilization in indolent lymphoproliferative disorders (LPD). We previously reported that only 34% of fludarabine-exposed patients mobilized successfully using granulocyte-colony stimulating factor (G-CSF; median 10 lg/ kg/day) with or without chemotherapy, with unpredictable kinetics and moderate infectious morbidity. Stem cell factor (SCF) plus high-dose twice daily (b.d.) G-CSF may improve mobilization in these patients. SCF 20 lg/kg/day subcutaneously was given from day 1, G-CSF 12 lg/kg b.d. subcutaneously from day 4, apheresis commenced from day 6. Previous study patients served as historical controls. Thirty five patients with indolent LPD were enrolled, median age was 54 years (range 31-66), 66% male, median cumulative prior fludarabine dose was 660 (405-900) mg. Overall, 22 patients (63%) collected X2.0 Â 10 6 /kg PBSC (success), compared to 34% controls (odds ratio (OR) 3.2; 95% confidence interval (CI) (1.2, 9.3); P ¼ 0.021). Median CD34 þ yield overall was 2.3 Â 10 6 / kg (0.53-8.97) from median four (2-6) aphereses. Study patients X50 years mobilized successfully more frequently than controls (58 versus 17%; P ¼ 0.0065). Adjusting for age, successful mobilization remained significantly higher in the current study (OR 4.2; 95% CI (1.4, 14.0); P ¼ 0.008). SCF/high-dose b.d. G-CSF improves PBSC mobilization efficacy after fludarabine exposure, over mobilization using G-CSF as the mobilizing cytokine. This combined growth factor strategy is a preferred mobilization method for fludarabine-exposed patients.

How I treat patients who mobilize hematopoietic stem cells poorly

“…39,40,121,122 However, the success rate is often still Ͻ 50%. Currently, the combinations of G-CSF, SCF, or, more recently, plerixafor with or without chemotherapy are probably the most promising approaches.…”

Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

“…22,23 This side effect is largely attributed to its cytotoxicity on hematopoietic stem cells. 24,25 Despite potent myelosuppression, therapyrelated myeloid neoplasms secondary to fludarabine single-agent treatment is extremely rare, reported 0 in 174 (0%) and 1 in 188 (0.5%) in two studies conducted on chronic lymphocytic leukemia/small lymphocytic lymphoma patients who received fludarabine as initial therapy with a long-term followup. 26,27 However, the incidence of therapy-related myeloid neoplasms is significantly higher in the setting of fludarabine combination therapy.…”

Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment

“…These results are not in line with those observed in other trials of the combination of SCF and G-CSF to improve PBPC collection. [18][19][20][21][22][23][24][25][26][30][31][32][33] The explanation might be that the present experimental arm was compared with standard chemotherapy plus G-CSF and included patients with malignant lymphoma, most of whom were heavily pre-treated before relapse or disease progression and even included patients with primary refractory disease.…”