Ancestim (SCF) and High-Dose Twice-Daily Filgrastim (G-CSF) Is Superior to G-CSF Alone or Cyclophosphamide Plus G-CSF for Mobilization of Peripheral Blood Stem Cells (PBSC) in Patients with Indolent Lymphoproliferative Disorders Previously Treated with Fludarabine; Results of a Historically-Controlled Phase-II Study.

Among patients (pts) with indolent lymphoproliferative disorders prior fludarabine (F) exposure is a risk factor for impaired PBSC mobilization. In a previous report of pts with prior F therapy (Leuk 18:1034Leuk 18:2004) only 14/41 pts (34%) achieved PBSC yields of ≥2 x 10⁶/kg from first mobilization using G-CSF (median 10 μg/kg/d) ± chemotherapy with highly variable timing of pheresis and moderate infectious morbidity. Given the synergy between G-CSF and SCF we hypothesized that SCF plus high-dose bd G-CSF would improve mobilization efficacy with more predictable timing of collections.

Methods: Ancestim (r-metHuSCF) 20 μg/kg/day sc was given from d1, G-CSF 12 μg/kg/bd sc from d4. Apheresis was scheduled from d6, provided PB CD34+ count was ≥3 x 10⁶/L. Pts from the previous study served as historical controls. The study had 80% power to detect an increase in successful mobilization to 65%.

Results: 35 pts were recruited and all are evaluable; median age 54 yrs (range 31–66), 66% male, 43% had CLL or PLL, 57% indolent NHL, similar to the historical cohort (p>0.05), and the median cumulative prior F dose of 660 (405–900) mg, was greater than the historical cohort (median 300 mg; p<0.0005). All study pts had received F in combination, usually cyclophosphamide and rituximab, with a median of 7 months (range 2–18) from last F-exposure. 69% of pts were in CR at the time of mobilization and 77% had no evidence of marrow infiltration, with 20% having mild to severely hypocellular marrow morphology. There were no severe adverse events, with 43% of pts having Gr 1–2 bone pain and 40% mild injection site reactions. 24 pts commenced apheresis as scheduled on d6, the reminder on d7–8. 22 pts (63%) collected ≥2.0 x 10⁶/kg PBSC (“success”) (p=0.021 vs controls) with a median CD34+ yield overall of 2.3 x 10⁶/kg (0.53–8.97) from a median of 4 (2–6) aphereses. Pts with a PB CD34+ count of >4.5 x 10⁶/L on the first day of apheresis had a 74% likelihood of achieving successful collection. We had previously reported that pts aged >50 yrs have a lower PBSC collection success, and adjusting for age the study pts were more frequently successfully mobilized (<50 yrs; 75% vs 53%. ≥50 yrs; 57% vs 18%; p=0.0085 adjusted for age). In contrast to prior reports, we found higher success rates with a shorter time elapsed since last F exposure [<6 Mo (89%), 6–9 Mo (63%), >9 Mo (40%); p=0.035]. In multivariate analysis, the only baseline factors associated with greater mobilization success were a shorter interval from last F-exposure and a lower cumulative chemotherapy toxicity score (Br J Haem 98:745, 1997). After adjusting for these factors, the use of the SCF and high-dose bd G-CSF schedule was still associated with a higher likelihood of mobilization success (p=0.005).

Conclusions: The regimen of SCF and bd high-dose G-CSF shows greater PBSC mobilization efficacy in pts previously treated with F than more commonly used strategies such as G-CSF alone or cyclophosphamide plus G-CSF, with good tolerance, predictable kinetics and no infectious morbidity. These data make this combined growth-factor mobilization strategy the preferred PBSC method for pts previously treated with F at our institution.