A comparison of cryopreserved and noncryopreserved peripheral blood hematopoietic stem cells for autologous transplantation in multiple myeloma: a study from the chronic malignancies working party of the EBMT

Introduction: Most transplant centres cryopreserve peripheral blood stem cells (PBSC) for use in a subsequent autologous hematopoietic cell transplant (AHCT) using Dimethyl sulfoxide (DMSO) as a cryoprotectant. Non-cryopreserved (NCP) PBSC are used in autologous transplants for multiple myeloma (MM) in some countries with limited resources. We compared AHCT outcomes between patients in a large tertiary referral transplant centre in Oran, Algeria, who received non-cryopreserved PBSC and patients from EBMT-affiliated centres in countries where cryopreservation is standard. Patients and Methods: MM patients who underwent AHCT between 2009 and 2020 inclusive using NCP PBSC were each matched with up to four patients from 420 EBMT-affiliated centres who received cryopreserved (CP) PBSC over the same period. Following standard procedures, PBSC were stored in a refrigerator at 4°C immediately following collection. PBSCs were then infused 24 hours following Melphalan administration (at a dose of either 140 or 200 mg/m²). The primary endpoints were neutrophil and platelet engraftment as defined by standard EBMT criteria. Secondary endpoints included non-relapse mortality (NRM), relapse incidence (RI), overall survival (OS) and progression free survival (PFS). Results: Using NCP PBSC, 407 MM patients were autografted. The median number of collection procedures was two (range (r), (1–3)). The mean PBSC viability was 95% (r, 93.8–98.5%). A total of 367 (90%) of these patients had at least one match with a patient in the EBMT registry who had received CP PBSC. In total, 1,412 CP PBSC patients were included in this analysis. In the NCP group, the median dose of PBSCs collected was 3.2 × 10⁶ CD34+ cells/kg (interquartile range (IQR, 2.4–4.5); for the CP group (available in 12% of cases), it was 4.0 × 10⁶ CD34+ cells/kg (IQR, 2.8–5.3) (P = 0.005). The median number of days to neutrophil engraftment for the NCP and CP cohorts were 12 (IQR, 11–14) days, and 12 (IQR, 11–13) days, respectively (HR comparing CP versus NCP 1.13, 95% CI 0.99–1.29, P = 0.08). The median time to platelet engraftment >20 × 10⁹/L was similar in the NCP and CP cohorts: 12 (IQR, 11–14) days and 12 (IQR, 11–14) days, respectively. Nonrelapse mortality rates at Day +100 were 0.3% (0.0–0.8%) and 0.7% (0.5–1.0%), respectively, in the NCP and CP groups (P = 0.38). The relapse incidence was lower in the NCP group (HR = 0.23, P = 0.004). The PFS up to 3 years post-transplant was significantly longer in the non-cryopreserved cohort (HR = 0.71, P < 0.001). The OS rates at 3 years were 81% and 82% in the NCP group and the CP group, respectively (P = 0.47). Conclusion: This EBMT registry study comparing the use of fresh stem cells with frozen stem cells did not find significant differences in either engraftment or NRM. The use of fresh stem cells is therefore an acceptable option in AHCT for multiple myeloma in countries with limited resources.