Advanced Osteolytic Lesions (OL), Mobilization and Collection of Hematopoietic Progenitor Cells (HPC) in Multiple Myeloma (MM)

Introduction: Presence of advanced OL was recently reported as a risk for poor mobilization in patients with multiple myeloma who had poor HPC collections (Jung et al. J Clin Apheresis 2014; Apr 25. doi: 10.1002). We sought to confirm this finding and also whether poor collection correlated with low peripheral blood CD34+ cell numbers as evaluated by flow cytometry.

Patients and Methods:

Patients: We performed a retrospective study of patients who underwent autologous HPC collection at our institution between 2005 and 2012 to identify poor mobilizers and mega-mobilizers in a 2:1 ratio for data analysis. We defined poor mobilizers as those who required maximal plerixafor support (4 days) for collection, and mega-mobilizers as those who collected >30 x 10⁶ CD34+ cells/kg in 2 days. We found 79 poor mobilizers, but removed 9 from data analysis because the collection variables of plerixafor timing and G-CSF dose differed from the others, leaving 64 myeloma (MM) and 6 non-myeloma plasma cell dyscrasias (NMPCD) patients for analysis: 41 male, 29 female, age range 43–86 (median 67.5). There were 37 mega-mobilizers: 36 MM, 1 NMPCD: 21 male, 16 female, age range 40–73 (median 61). Cumulative CD34+ cells/kg during leukapheresis and peak peripheral CD34+ cell counts were recorded.

Apheresis: Apheresis was initiated using a central venous catheter when the predicted CD34+ cell collection for 30 L of blood processed was at least 1 x 10⁶/kg using a predictive formula (Rosenbaum et al. Cytotherapy 2012; 14(4): 461-6). The volume of blood processed each day was based on the same predictive formula, and ranged from 5 to 30L. Cells were collected on a COBE ® Spectra apheresis machine, software version 7.0, using 1000 mL anticoagulant citrate dextrose (ACD) and 5000 units heparin for anticoagulation at an inlet:anti-coagulant ratio of 31:1, and an inlet flow rate of 150 mL/min with anti-coagulant infused at 5 mL/min. The collection flow rate was set at 1.5 mL/min and 10 mL ACD was added to the component at processed volumes of 10 L, 20 L and 30 L. An infusion of 2 g calcium chloride in 250 mL normal saline (0.9% sodium chloride) ran at 85 mL/h.

Flow cytometry: CD34+ cells in peripheral blood and HPC products were quantified by flow cytometry using the ISHAGE protocol.

Statistics: Mean peripheral blood CD34+ cells/µL and mean CD34+ cells/kg collected were calculated separately for the mega-mobilizer + poor mobilizer combined group, mega-mobilizer and poor mobilizer groups. All patients were subcategorized into those with ≤10 and >10 OL, and means for CD34+ cells/kg collected and peripheral blood CD34+ cells/uL were compared separately between the ≤10 and >10 OL groups using two-tailed Student’s t-tests and p-values evaluated for significance.

Results: For all patients combined (mega + poor mobilizers) there were no significant differences in either peripheral CD34+ cells/µL or mean total CD34+ cells/kg collected between the ≤10 and >10 OL subgroups. Mean CD34+ cells/µL peripheral blood was 276 and 250 for the ≤10 and >10 OL groups, respectively (p=0.73), with means of 27.7 and 23.6 CD34+ × 10⁶ CD34+ cells/kg collected (p=0.41). For the mega-mobilizers there was no significant difference in mean peripheral blood CD34+ cells/µL between the OL (</=10 and >10) groups (722 vs. 709, respectively; p=0.92) or in total CD34+/kg collected (55.8 and 53.8, respectively; p=0.78). For the poor mobilizers there was no significant difference in mean peripheral CD34 cells/µL between the ≤10 and >10 OL groups (27 and 20, respectively; p=0.10); however, there was a statistically significant difference in total number of CD34+ cells/kg collected, 11.9 and 8.4 ×10⁶ CD34+ cells/kg, respectively (p=0.02).

Conclusion: No significant difference was seen in mobilization as judged by peripheral blood CD34+ cells/ µL in mega-mobilizers or poor separately or combined, but a difference in the total number of CD34+ cells collected was seen in poor mobilizers. We suggest this difference results from variables in collection protocols, as we have previously shown that both mobilization and collection variables impact total CD34+ cells collected by apheresis (Abuabdou et al 2013; J Clin Aph Dec 18. doi: 10.1002).