Volume determination methods for hematopoietic progenitor cell products collected by apheresis.

BACKGROUND AIMS: CD34+ cell count of hematopoietic progenitor cell products is often first determined using a product sample, with the final reported cell count obtained by multiplying cell count from the sample by the total product volume. Product volume may be determined by apheresis instruments used for collection or calculated based on specific gravity (SG). Here the authors sought to determine the discrepancies between these methods and the impact on patient care. METHODS: A total of 262 products collected from 176 donors by apheresis were retrospectively reviewed. Volumes calculated by apheresis instruments were compared with volumes calculated based on SG. CD34+ cell/kg doses based on volumes from apheresis instruments and SG were also compared. Furthermore, among 42 patients who required multiple collections, the authors determined whether different calculation methods would have changed the number of procedures required. RESULTS: The volumes for 253 products (96.6%) and CD34+ cell/kg doses for 257 products (98.1%) generated from apheresis instruments and SG were similar. Products with discrepant volumes when calculated using different methods were not associated with delayed engraftment. Forty patients who underwent multiple collections (95.2%) were under their collection goals during their first collection and would have required multiple procedures regardless of which method was used to calculate product volumes. CONCLUSIONS: Volumes determined based on SG did not provide a clear benefit over volumes determined by apheresis instruments. Hence, variation in volume calculation methods across different laboratories is likely to lead to minimal impact on patient care.

Adverse events of cryopreserved hematopoietic stem cell infusions in adults: a single-center observational study.

BACKGROUND: Autologous hematopoietic stem cell (HSC) transplantation has been used for almost three decades for the management of malignant hematologic diseases and some solid tumors. Dimethyl sulfoxide (DMSO) is used as a cryoprotective agent for hematopoietic progenitor cells (HPCs) collected by apheresis (HPC-A). We evaluated the factors contributing to the occurrence of adverse events (AEs) of cryopreserved HPC-A infusion. STUDY DESIGN AND METHODS: Between January 2009 and June 2014, a total of 1269 (1191 patients) consecutive HPC-A infusions were given to adult patients undergoing autologous HSC transplantation at Barnes-Jewish Hospital. Only infusions on the first day of transplant were included in the analysis. RESULTS: AEs were reported in 480 (37.8%) infusions. The most common AEs were facial flushing in 189 (39.4%) infusions, nausea and/or vomiting in 183 (38.1%) infusions, hypoxia requiring oxygen in 139 (29%) infusions, and chest tightness in 80 (16.7%) infusions. Multivariate analysis using logistic regression showed that female sex (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40-2.26; p < 0.0001), diagnosis other than multiple myeloma (OR, 1.44; 95% CI, 1.12-1.84; p = 0.004), larger volume of infusion per body weight (OR, 1.66; 95% CI, 1.29-2.15; p < 0.0001), and number of granulocytes infused per body weight (OR, 1.30; 95% CI, 1.01-1.67; p = 0.042) were significant predictors of occurrence of AEs during infusion. CONCLUSION: AEs due to HPC-A infusion occurred in more than one-third of patients. Interventions need to be instituted to reduce AEs and thus improve the safety of HPC-A infusion. Many of these toxicities can be attributed to DMSO, and this is reflected in the volume of infusion. It might be warranted to consider implementing DMSO-reducing protocols before infusion.

Sterility testing of apheresis hematopoietic progenitor cell products using an automated blood culture system.

BACKGROUND: AABB Standards require monitoring of hematopoietic progenitor cell (HPC) products for microbial contamination. To date, there is no automated blood culture system cleared by the Food and Drug Administration for this application. Our objective was to validate the VersaTREK system (TREK Diagnostic Systems) for sterility testing of apheresis HPC products. STUDY DESIGN AND METHODS: Four aerobic bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis, and Bacillus cereus), five anaerobic bacteria (Fusobacterium necrophorum, Clostridium perfringens, Bacteroides fragilis, Prevotella loescheii, and Propionibacterium acnes), and one fungus (Candida albicans) were spiked into apheresis HPC products at concentrations of 10, 10(2) , 10(3) , and 10(4) colony-forming units (CFUs)/mL. Aerobic and anaerobic bottles were incubated until positive or for up to 5 days. DNA was simultaneously extracted for polymerase chain reaction amplification of 16S ribosomal RNA (rRNA) gene. RESULTS: All aerobic bacteria grew in both bottles at all concentrations tested within 24 hours, and the time to positivity (TTP) was significantly shorter with aerobic bottles. C. albicans grew in the aerobic media at all concentrations within 30 hours. Anaerobes grew in the anaerobic bottle at all concentrations within 5 days. No bacteria were detected by using 16S rRNA gene amplification at 10(4) CFUs/mL. CONCLUSION: Compared to culture, 16S rRNA gene amplification of HPCs does not improve sensitivity or turnaround time for HPC sterility testing. The VersaTREK system is a reliable tool for detecting microbial contamination of apheresis HPC products with a limit of detection of less than or equal to 10 CFUs/mL. Inclusion of both the aerobic and the anaerobic culture bottles achieves the shortest TTP for all species tested.

Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.

The purpose of this article was to examine historic institutional autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for autologous transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of > or =2 x 10(6) CD34(+) cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34(+) cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected > or =2 x 10(6) CD34(+) cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34(+) cell yield and required less aphereses to collect > or =2 x 10(6) CD34(+) cells/kg. Mobilized, preapheresis, peripheral blood CD34(+) count correlated with first day apheresis yield (r = .877, P < .001) and 20 cells/microL was the minimum threshold needed for a successful day 1 collection. For the remobilization analysis we included patients from the whole database. A total of 269 of 1834 patients underwent remobilization using G/C, G-CSF, and/or GM-CSF, and G-CSF plus plerixafor. Only 23% of remobilized patients achieved > or =2 x 10(6) CD34(+) cells/kg and 29.7% failed to pool sufficient number of stem cells from both collections. Patients receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients remobilized with G-CSF who waited > or =25 days before remobilization had lower CD34(+) cell yield than those who waited < or =16 days, P = .023. Current mobilization regimens are associated with a substantial failure rate irrespective of underlying disease. Patients who fail initial mobilization are more likely to fail remobilization. These findings suggest that there is a need for more effective first-line mobilization agents.