Stem Cell Mobilization using G-CSF plus Plerixafor in multiple myeloma- A Single Center Five Years

Introduction/Background/Significance: Plerixafor is an inhibitor molecule with ability for reversible binding to CXCR-4 receptor – followed by superior stem cell (SC) release/mobilization into peripheral blood (PB). The use of G-CSF plus plerixafor increases the ratio of patients (pts) that respond to the SC-mobilization ("good-mobilizers") and enables harvesting of enough cells for autologous SC-transplant (ASCT). The study aim was to evaluate the efficacy of G-CSF plus plerixafor mobilization regimen (compared to G-CSF alone) on the basis of CD34⁺ yield in the cell harvest and hematopoietic reconstitution after ASCT.

Materials and Methods/Case Presentation/Objective: This study included 181 pts with multiple myeloma (MM), underwent to CD34⁺ cell mobilization and ASCT. For 121/181 (66.9%) pts cyclophosphamide, doxorubicin, dexamethasone (CAD) chemotherapy with G-CSF or G-CSF plus plerixafor mobilization was used ("chemotherapy-mobilized" pts). The ratio of "steady-state-mobilizations" (only G-CSF or G-CSF plus plerixafor) was 60/181 (33.1%). "Mobilization-failure" was proven in 88/181 (48.6%) pts ("poor-responders"; CD34⁺ cell count ≤ 40 per μL of PB) and they received G-CSF plus plerixafor regimen. Among them one dose of plerixafor (240 μg/kg bm subcutaneously) was given to 79/88 (89.8%) and two doses (ampules) were administered to 9/88 (10.2%) pts. PB cells were collected by Spectra-Optia (Terumo-BCT; USA). Typically, central venous (subclavian or jugular) catheter was used as vascular access. Cells were cryopreserved by controlled-rate freezing using 10% dimethyl sulfoxide and stored at –140 ± 10 °C. Data obtained were compared concerning the cell harvesting protocol, CD34⁺ cell quantification, SC-engraftment potential and pts' clinical outcome.

Results/Description/Main Outcome Measures: "Chemotherapy-mobilized" pts required rarely plerixafor administration (34/121; 28.1%; p=0.01) compared to "steady-state-mobilizations" – when it was required to apply plerixafor in 45/60 (75%) of treated pts. The median CD34⁺cell count on the apheresis day was 61 cells per μL of PB (range: 14 – 594). The CD34⁺ cell yield (all pts) was 8.7x10⁶/kgbm in the harvests in average. Pts requiring plerixafor achieved lower (7.6x10⁶/kgbm), but still comparable CD34⁺ cell yields – to be able to perform a tandem ASCTs. The cell doses infused was in correlation with engraftment kinetics – suboptimal CD34⁺ doses resulted in delayed hematopoietic recovery (p < 0.001). Neutrophil engraftment was confirmed on the 11^th day (range: 9 – 18) in average. Pts requiring plerixafor had inferior (p = 0.029) platelet engraftment kinetics: the mean platelet recovery was detected on the 12^th day (range: 10 – 21 for G-CSF group) and on the 13^th day (range: 11 – 26 in G-CSF plus plerixafor group), respectively.

Conclusions: The use of G-CSF plus plerixafor protocol reduces the rate of "mobilization-failure" and provides an adequate cell dose for ASCT (including tandem transplants) – with superior therapeutic potential and safety profile of treatment. Further controlled, larger clinical trials concerning correlation of the applied CD34⁺ cell count and efficacy of ASCTs are required.