A Novel Hematopoietic Progenitor Cell (HPC) Mobilization Regimen, Utilizing Bortezomib and Filgrastim (G-CSF), for Patients Undergoing Autologous HPC Transplant (AHPCT) for Multiple Myeloma (MM) and Non-Hodgkin's Lymphoma (NHL)

Adequate HPC collection is critical for patients undergoing AHPCT.  HPC mobilization is usually done with G-CSF, which affects the stromal derived factor-1a interaction with HPC.  Other adhesion molecules also play a role in HPC mobilization e.g. very late antigen-4 (VLA-4) expressed on HPCs, and its ligand, vascular cell adhesion molecule-1, expressed on the bone marrow microenvironment.  Bortezomib, a proteasome inhibitor, has been shown to down regulate VLA-4.  In this study, bortezomib was used with G-CSF to mobilize and collect HPC for AHPCT.  Sixteen patients (11 males), aged 42 – 70 years, with MM (n=9) or NHL (n=7,) undergoing AHCPT for the first time, were enrolled after obtaining consent.  Patients with >grade II neuropathy or platelet count <100K/ml were excluded.  Bortezomib was administered on days -11 and -8 at a dose of 1.3mg/m² iv, followed by G-CSF 10mg/kg sc, on days -4 to -1 prior to HPC collection (day 0). Results were compared with matched patients with MM or NHL undergoing AHPCT at our Institution. All patients had CD34⁺ cell enumeration from the peripheral blood on the day of collection, and followed a published Institutional algorithm regarding the use of plerixafor.  If the CD34⁺ cell count was adequate, patients underwent a high volume HPC collection, if the CD34⁺ count was <5/ml, then they received plerixafor.  In this study, one patient (6%) had CD34⁺ cell count of 3.9/ml on day 0 and received plerixafor, as compared to 33% of matched historical controls.  Botezomibr was well tolerated and all patients had adequate HPC collections with no mobilization failures.  10 patients completed HPC collection in one day and 7 in two days.  All patients had timely neutrophil and platelet engraftment post AHPCT. Bortezomib + G-CSF is an effective HPC mobilizing regimen worth investigating in subsequent studies.  Bortezomib also has known anti MM and NHL effects.