Poor Mobilization of CD34+ Stem Cells Predicts Inferior Relapse and Survival Outcomes After Autologous Stem Cell Transplantation for Multiple Myeloma

Autologous stem cell transplantation (ASCT) remains the standard upfront therapy of younger patients with multiple myeloma (MM). Identifying a prognostic threshold amount of mobilized CD34+ hematopoietic stem cells (SC) may become an important modifiable parameter in the era of novel stem cell mobilization strategies. While poor mobilization of CD34+ cells has been shown to cause delays in hematopoietic recovery, the data on long-term clinical outcomes of patients with inferior CD34+ SC collection (‘under mobilizers’) are limited. We analyzed prospectively collected data on 239 adult patients with MM who underwent ASCT at our institution from 01/1996 to 12/2009. Fifty-one patients (21.3%) who collected less than 4 × 10⁶/kg CD34+ SC were classified as ‘under mobilizers’ and were compared to the rest of the study population (n=188) who collected ≥ 4 × 10⁶/kg CD34+ SC. Even though under mobilizers were slightly older (median 59 vs. 54 years, p =0.01), had longer time from diagnosis to ASCT (11 vs. 8 months, p =0.05), and required more days of leukapheresis (5 vs. 3 days, p <0.001), they did not differ from the other group according to the number of prior treatment regimens, mobilization method (only 2 patients received plerixafor), performance status, or disease remission status at transplant (all p >0.2). Median time-to-recovery for both neutrophils (11 vs. 10 days, p <0.001) and platelets (13 vs. 12 days, p <0.001) was delayed among under mobilizers. Under mobilizers had worse relapse-free survival (RFS) (hazard ratio [HR]=1.49, 95% CI, 1.03–2.16, p =0.03) and non-relapse mortality (NRM) (HR=3.59, 95% CI, 1.51–8.56, p <0.01) in multivariable Cox proportional hazards analysis. Even though the association between poor CD34+ SC collection and inferior overall survival did not reach statistical significance (HR=1.42, 95% CI, 0.94–2.16, p =0.1), under mobilizers were found to have significantly higher rates of 100-day post-transplant mortality (p =0.02). We conclude that in the context of ASCT for MM, failure to collect ≥ 4 × 10⁶/kg CD34+ SC is independently associated with worse RFS and NRM.