A Phase II Study of Peripheral Blood Stem Cell (PBSC) Mobilization Using Stem Cell Factor (SCF), Filgrastin (G-CSF), and Cyclophosphamide (CY) in Patients at High Risk for Mobilization Failure.

Background: Inability to collect adequate numbers of PBSCs remains an obstacle to curative ASCT in heavily pretreated patients with relapsed or refractory lymphoma and other malignancies. Retrospective data from our institution have shown that pts with greater exposure to marrow toxic agents have only a 50% rate of successful stem cell collection versus 87% in pts with lesser exposure. We identified heavily pretreated patients at high risk of mobilization failure as rated by a previously validated chemotherapy scoring system (

Methods: Pts with acute myeloid leukemia (AML) or relapsed/refractory Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL) with a chemotherapy score >42 were eligible. Following completion of salvage or consolidation chemotherapy, consenting patients were mobilized with CY 2.5 g/m²(day 1), SCF 20 ug/kg/day and G-CSF 10 ug/kg/day, both starting day 4, and continuing until completion of leukapheresis. PBSC collection began day 11 (if PB CD34 cells were >5/mL) and continued to a target of 2 x 10⁶ CD34+ cells/kg or for a maximum of 5 days.

Results: Twenty-seven pts were enrolled. Diagnoses: NHL n=22; HD n=1; AML n=4. M:F ratio = 14:13; median age 52 yrs (range 17–63); time from diagnosis to study entry, median 18 mos (range 5–70 mos). Nineteen of 23 lymphoma pts received 6–8 cycles of CHOP/ABVD followed by salvage chemotherapy. The other 4 pts had transformed lymphoma and received CVP or chlorambucil prior to transformation. Sixteen pts responded after 1 salvage regimen; 7 pts required 2 salvage regimens [ESHAP, GDP, DHAP, miniBEAM, or CHOP (for transformed pts)]. AML pts were in CR at time of study entry and had received ≥2 consolidation cycles with high-dose cytarabine. Sixteen of 27 pts (59%)[95% CI 44–78%] were successfully collected (median of 3.21x 10⁶ CD34+ cells/kg (range 2.21–14.41) in a median of 1 apheresis (range 1–5; 11 were collected with a single apheresis). However, 3 of the 4 AML pts did not mobilize. Neutrophils <1.0x10⁹/L and platelets <50x10⁹/L (grade 3) on day 11 (start date for apheresis) were the only factors found to be predictive of collection failure. Age, gender, baseline bloodcounts, LDH, BM involvement, duration of disease, and disease status at study entry (CR/PR) were not associated with mobilization outcome. There were no significant allergic or anaphylactic reactions to the SCF and no grade 4 toxicities seen.

Summary: The combination of SCF, G-CSF, and CY results in successful PBSC mobilization in 59% of pts at high risk of failure due to prior heavy chemotherapy exposure. This success rate is not significantly improved over the estimated 50% expected rate with standard G-CSF and CY mobilization. Nevertheless, our approach of selecting high risk pts for alternative strategies may be more rational than incurring the costs and toxicities of repeated mobilization attempts.