Optimal infused CD34⁺ cell dose in multiple myeloma patients undergoing upfront autologous hematopoietic stem cell transplantation

Autologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34⁺ cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 10⁶ cells/kg) and high (>2.5 × 10⁶ cells/kg) CD34⁺ dose groups. We included 2479 patients, 95 in the low CD34⁺ group and 2384 in the high CD34⁺ group. Patients in the low CD34⁺ group were older (63.2 vs 61.1 years, p = 0.013), more often had R-ISS III (19% vs 9%, p = 0.014), received plerixafor (60% vs 35%, p < 0.001) and transplanted after 2009 (88% vs 80%, p = 0.047). Time to neutrophil and platelet recovery was longer in the low CD34⁺ group. Median PFS and OS were lower in the low CD34⁺ group (31.6 vs. 43.6 months, p = 0.011 and 76.4 vs. 108.2 months, p < 0.001, respectively). Evaluation of incrementally higher CD34⁺ dose did not show significant improvement in survival at thresholds >2.5 × 10⁶ cells/kg. Multivariable analysis affirmed that CD34⁺ >2.5 × 10⁶ cells/kg was associated with better PFS (HR 0.71, p = 0.008) and OS (0.59, p < 0.001). After propensity score matching, a CD34⁺ dose >2.5 × 10⁶ cells/kg remained a predictor of better OS (0.42, p < 0.001). In conclusion, CD34⁺ dose >2.5 × 10⁶ cells/kg was associated with improved survival, without any additional benefit at incrementally higher doses.