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Introduction: Knowledge of cryopreservation of Hematopoietic Progenitor Cells (HPC) collected by Bone Marrow aspiration (HPC,BM) is limited. Aim: To describe the experience of a Cell Processing Center with HPC,BM cryopreservation for therapeutic use, and to compare the BMT outcomes with non-cryopreserved historical controls. Methods: This is a nested case-control study. The casuistry consisted of 16 HPC,BM units cryopreserved between 2020 and 2022. The HPC,BM units were Red Blood Cells (RBC) depleted using Hydroxyethyl Starch (HES) 450/0.7, followed by centrifugation for volume reduction. The units were frozen in a mechanical freezer at -80°C after adding the cryopreservation solution (5%HES/5%DMSO) and stored in the LN2 vapor phase. Data from patients whose HPC,BM unit was RBC depleted and freshly infused were used as historical controls. The control for one case of cryopreserved HPC,BM for autologous transplantation was one cryopreserved HPC,PB. Controls were matched to cases by diagnosis. Results: The mean age of cases was 29.4 ± 11.1 years. Nine (56.3%) patients were female. One (6.3%) unit was cryopreserved for autologous use and fifteen (93.8%) for unrelated allogeneic BMT. One (6.3%) patient had neuroblastoma, one (6.3%) SCID, one (6.3%) CML, three (18.8%) AML, one (6.3%) Griscelli syndrome, two (12.5%) Wiskott-Aldrich syndrome and four (25%) ALL. Twelve (75%) units were released for therapeutic use, of which ten (83.3%) already have grafting data available. The mean time to neutrophil and platelet engraftment was 16.8 and 18.4 days, respectively. One (11.1%) patient had graft failure. There was no difference in time to neutrophil and platelet engraftment between cases and controls. Related to adverse effects during infusion, the frequency of nausea and hemoglobinuria was higher in controls (40% vs. 14.3%, respectively), while the frequency of hypertension was higher in cases (20% vs. 57.1%, respectively), although not significant. The occurrence of fever was significantly higher in controls when compared to cases (60% vs. 0%, p = 0.045). Although not significant, pseudomembranous colitis (0% vs. 25%, respectively) was more frequent in cases, while mucositis (50% vs. 12.5%, respectively) was more frequent in controls. Acute GVHD was not observed in cases and controls during the observational period. Cox regression analysis adjusted for age, sex, transplant center, and infused CD34+ cell dose showed no significant difference in the occurrence of death or grafting failure between cases and controls. Discussion: The higher frequency of fever in the controls can be explained by the fresh infusion of the product collected in an open system with frequently observed contamination. Cryopreservation allows clinical, regulatory, and logistical procedures, including cell therapy product quality control testing. Therefore, cryopreservation permits the identification and sensitivity of the microorganism in case of a positive test and the knowledge of results by the transplant staff. There was no difference in the other transplant outcomes when cases were compared with controls. However, the low number of individuals may have resulted in a lack of statistical power to detect associations, especially for variables with missing observations. Conclusion: This study indicates that HPC,BM cryopreservation was not associated with an increased occurrence of adverse effects during infusion, BMT complications, and graft failure or death. |
