Absolute Lymphocyte Count (ALC) Recovery in Multiple Myeloma (MM) Patients after Autologous Stem Cell Transplant (ASCT) Is Related to CD34+ Dose-Infused

BACKGROUND: Preliminary data presented by our group at the 2014 ASBMT meeting suggested a correlation between higher CD34+ Cell-Dose Infused (CD34-CDI) during ASCT and shorter time to ALC recovery for MM patients (pts). This updated analysis which includes additional pts with longer follow-up supports our prior results, and suggests a correlation between higher CD34-CDI and decreased incidence of infections.

METHODS: From 1/2012 - 1/2014, 21 consecutive MM pts who had undergone ASCT were evaluated retrospectively to determine the impact of CD34-CDI on ALCs and infectious events. During the first 100 days post-ASCT, all infectious complications were noted and ALCs collected. Overall survival and progression free survival were monitored. ALC recovery was defined as the first day of three consecutive measurements for the cutoff values: ALC ≥ 800, ALC ≥ 1000, and ALC ≥ 1500. Cox proportional hazard models were applied to evaluate the association of CD34-CDI to ALC recovery. The significance of the association was assessed using the Log Rank Test since no competing risks were identified. Additionally, the Nonparametric Wilcoxon Rank Sum Test was used to determine the relationship between CD34-CDI and the development of any infectious events.

RESULTS: Of the 21 patients, 81% were male, 19% were female. Median age was 62 years (range 45-71). Majority (62%) had IgG MM and kappa light chain restriction (86%). Approximately 62% had ISS Stage II/III disease. Patients who had received a higher CD34-CDI were more likely to achieve ALC ≥ 800 (p=0.040) and ALC ≥ 1000 (p=0.021). For ALC recovery defined as ALC ≥ 1500, no statistical significance was observed (p=0.27). When CD34-CDI was < 4x10⁶ cells/kg, median times to ALC ≥ 800 and ALC ≥ 1000 were 33.5 and 41.5 days respectively, and were 19 and 22 days when CD34-CDI was > 4x10⁶ cells/kg. Pts without infections tended to have higher CD34-CDI compared to those pts with infections (p=0.0452). Five of six pts with CD34-CDI < 4x10⁶ cells/kg, and three of 15 pts with CD34-CDI > 4x10⁶ cells/kg developed at least one bacterial infectious complication. Among pts who received CD34-CDI < 4x10⁶ cells/kg, 60% of infections (9 out of 15 events) occurred.  With 17 months (mo) of median follow-up (range 9 - 30 mo), five pts have relapsed and one death has occurred. Four of five relapses, and the one death received CD34-CDI > 4x10⁶ cells/kg.

CONCLUSION: Higher CD34-CDI (> 4x10⁶ cells/kg) may shorten time to ALC recovery and limit infectious complications. Most relapses to date occurred in pts transplanted with CD34-CDI > 4x10⁶ cells/kg, raising the question of product contamination with higher cell-doses.  Additional follow-up and larger prospective trials are needed to further define optimal CD34-CDI that balances the benefits of shortened time to ALC recovery, minimizing infectious complications, and decreasing risk of product contamination.