Impact of CD34+ Cell-Doses Given during Autologous Stem Cell Transplantation on Absolute Lymphocyte Recovery in Multiple Myeloma Patients

BACKGROUND:  CD34+ cell-doses given during autologous stem cell transplantation (ASCT) for multiple myeloma (MM) patients (pts) can vary between pts depending on ability to mobilize CD34+ cells and amount of CD34+ cells/kg collected during the apheresis procedure. Published retrospective studies suggest that absolute lymphocyte count (ALC) recovery may be a predictor of overall survival (OS), progression free survival (PFS), and infectious complications in ASCT. It is unclear whether there is an optimal CD34+ cell-dose that correlates with a shorter time to ALC recovery, possibly decreasing infectious complications, and potentially increasing time to relapse.

METHODS:  A retrospective analysis of ALC recovery was performed on 12 consecutive MM pts who had undergone ASCT from 1/2012 to 1/2013 at the University of Virginia to determine if a relationship existed between CD34+ cell-dose given during ASCT and ALC recovery. For each pt, number/type of infection and ALCs were collected for the first 100 days post-ASCT. OS and PFS were also assessed for each pt. Cox proportional hazard models were used to estimate the association of CD34+ cell-dose infused with time to ALC recovery after ASCT. ALC recovery was defined as the first day of three consecutive measurements for three different cutoff values: ALC ≥ 800, ALC ≥ 1000, and ALC ≥ 1500. No competing risks occurred; therefore, the log rank test statistic was used to assess the significance of the association. 

RESULTS: Median age was 60 years (range from 45-71 years), 75% were male, 67% had IgG MM, and 92% had kappa light chain restriction. Fifty-eight percent had ISS Stage I MM and 33% had ISS Stage III disease. The analysis revealed that a higher CD34+ cell-dose given during ASCT showed a trend toward faster ALC recovery, when defined as ALC ≥ 800 (p=0.043) and ALC ≥ 1000 (p=0.052). No difference was seen for ALC ≥ 1500. Median times to achieving ALC ≥ 800 and ALC ≥ 1000 were 43 and 59 days, respectively for pts given CD34+ cell-dose < 4x10⁶ cells/kg; and were 18 and 19 days for pts given CD34+ cell-dose > 4x10⁶ cells/kg. All five pts transplanted with a CD34+ cell-dose < 4x10⁶ cells/kg developed at least one bacterial infection. Only one of the seven pts transplanted with CD34+ cell-dose > 4x10⁶ cells/kg developed bacterial complications. Eighty-two percent of bacterial infections (n=11) occurred in pts given CD34+ cell-dose < 4x10⁶cells/kg.  Median time of follow-up was 12 months (range from 9 to 20 months). Two pts have relapsed, at 10 and 13 months, post-ASCT and no deaths have occurred.

CONCLUSION:  These preliminary results suggest that CD34+ cell-dose > 4x10⁶ cells/kg given during ASCT for MM may be associated with shorter ALC recovery and lower rates of infections. However, larger prospective trials with longer follow-up are necessary to further define optimal CD34+ cell-dose infusion for ASCT in MM pts in order to improve ALC recovery.