Pre-apheresis Peripheral CD34 Research Articles

Elevation of Serum Pro-Brain Natriuretic Peptide in G-CSF Stimulated Hematopoietic Progenitor Cell Donors

Introduction:Healthy donors who are treated with GCSF before peripheral blood hematopoietic progenitor cell (HPC) collection may develop side effects and aberrant laboratory values that have been described with the mobilization regimen. Alternatively, unexpected abnormal laboratory results could reflect occult complications or underlying disease. While many serum chemistry test results are affected by G-CSF, there have been no published reports describing an effect on BNP (pro-brain natriuretic peptide), a serum marker of heart failure. We encountered a donor who developed an elevated BNP after GCSF-stimulated HPC collection, and investigated its possible association with GCSF administration in healthy donors.Case Report:A 41-year old woman was evaluated for matched allogeneic peripheral HPC donation. History and physical exam were unremarkable, and standard laboratory values, EKG and chest X-ray revealed no abnormalities. The donor was mobilized with 10mcg/kg GCSF daily for 5 days. Her only complaint was of headache starting on day 4 that was relieved partially with acetaminophen. No other side effects were recorded.Her pre-apheresis peripheral CD34+ count was 87/mcL. At the start of apheresis HPC collection, the donor reported headache 7/10 in intensity and intolerance to light, unrelieved by acetaminophen but partially relieved with oxycodone. She complained of nausea during collection, but the procedure was otherwise successful and uneventful (15L of whole blood processed). Her headache persisted at the time of discharge, and the donor was counseled and prescribed one additional dose of oxycodone.Five hours after discharge the donor reported “the worst headache of her life”, nausea and difficulty breathing. She was evaluated at the ER, where she had stable vital signs and normal oxygen saturation. Her physical exam was unremarkable. Head CT was negative for intracranial hemorrhage or mass effect. A panel of laboratory analyses revealed leukocytosis, decreased platelets, and increased alkaline phosphatase and liver enzymes, which are documented findings associated with GCSF stimulation and large-volume apheresis. Given the donor’s complaint of dyspnea, serum BNP was measured and found increased to 483pg/mL (normal <124pg/mL). The donor had a normal pulmonary examination and no clinical evidence of cardiac insufficiency; a chest X-ray and an echocardiogram were also within normal limits. Her symptoms resolved with IV hydromorphone and she was discharged in stable condition. A follow-up serum BNP 4 weeks after donation was within normal range (105pg/mL).Investigation:A preliminary study evaluated 11 additional HPC donors who were stimulated with 10mcg/kg GSCF for 5 days (Table 1). Nine of twelve (75%) donors were male, and seven were Caucasian. Ten of the total 12 donors demonstrated an increase in BNP levels compared to pre-stimulation results. Follow-up of four total donors 9-17 days after donation demonstrated return of BNP levels to baseline. None of the donors had clinical evidence of heart failure during stimulation, donation, or follow-up. The average increase in BNP was 4.2 fold, and in a total of 3 donors it exceeded the normal range for the laboratory. The presence or degree of BNP elevation did not correlate with age, gender, severity of GCSF side effects, liver panel results, or pre-apheresis peripheral CD34+ count.Conclusion:This case and preliminary study indicate that an increase in BNP levels can be observed in approximately 80% of HPC donors stimulated with 5 days of 10mcg/kg GCSF. The increase in BNP in these donors is not associated with ventricular dysfunction or symptoms of cardiac congestion, and it returns to baseline levels in 2-4 weeks. Two possible molecular mechanisms for this BNP increase include 1) activation of gp130 by increased circulating cytokines associated with GCSF; or 2) direct transcriptional activation of the BNP gene by cardiomyocyte GCSF receptor activation of the JAK-STAT pathway. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prospective Randomized and Crossover Comparison of Two Apheresis Machines for Peripheral Blood Stem and Progenitor Cell Collection: A Multicenter Study

Peripheral blood stem and progenitor cell (PBSPC) collection imposes apheresis-related risks including thrombocytopenia, hypocalcemia and thromboembolism in donors for PBSPC transplantation. Efficient PBSC collection with fewer apheresis risks and less contamination in the collected products is crucial and we have shown some distinct characteristics among apheresis devices (Transfusion, 2003, 2007 and 2014). A recently introduced apheresis device for PBSPC collections, Spectra-Optia, has not yet established supremacy in safety and efficiency over other established previous apparatuses/programs. To compare the Optia with the widely used automated program for a former apheresis machine, Spectra-Auto (Software version 6.1), we for the first time carried out a prospective randomized multicenter and crossover study for a total of 233 apheresis done from November 2013 to May 2015 in adult (≥18 years) and G-CSF-given patients/donors. The device for the first-day apheresis was randomly assigned, and a total of 152, consisting of 47 for autologous (auto-) patients and 105 for allogeneic (allo-) donors, were studied (1st-day analysis). Among them, the 81 subjects who required the second-day apheresis to collect more cells, the second-day apheresis was performed with the other machine than the one used in the first day, and apheresis collections for 2 consecutive days using both machines were compared by a paired-t test (crossover analysis). In the both devices, apheresis was performed based on the manufacturer's protocols, with 12:1 to 15:1 ratios of whole blood to acid citrate dextrose without heparin. There was no difference between the Optia (n = 74) and the Spectra-Auto (n = 78) in the pre-apheresis parameters including age, sex, circulating blood volume (CBV), and peripheral complete blood counts (CBCs). In the crossover comparison, age, sex and CBV were technically same and CBCs were similar between the two machines (n = 81 in each). The Spectra-Auto processed larger volumes compared with the Optia [P = .02 (1st-day analysis) and .08 (crossover analysis)], although run time was similar with the two devices [P = .57 (1st-day) and .52 (crossover)]. Mild apheresis-related reactions occurred in both machines with similar frequencies of reactions, and volumes of ACD used were not different between them. Volumes of harvested products were greater in the Optia compared with the Spectra-Auto [158 vs. 95 mL, P < .01 (1st-day) and 137 vs. 86 mL, P < .01 (crossover)]. Yields of mononuclear cells [P = .27 (1st-day) and .22 (crossover)] and CD34+ cells [P = .10 (1st-day) and .19 (crossover)] were not different between them. However, regardless of program, pre-apheresis peripheral CD34+ cell counts strongly correlated with the number of CD34+ cells collected, and collection efficiencies of CD34+ cells were significantly higher in the Optia compared with the Spectra-Auto [82.2% vs. 66.3%, P < .01 (1st-day) and 80.5% vs. 63.1%, P < .01 (crossover)]. The products collected using the Optia contained more contaminating red blood cells [64 vs. 36 x 106 cells, P < .01 (1st-day) and 56 vs. 33 x 106 cells, P < .01 (crossover)], compared with the Spectra-Auto, without corresponding anemia. Only in crossover analysis, there was a trend that contaminated platelets were higher with the Optia compared with the Spectra-Auto (154 vs. 127 x 109 cells, P = .06). In conclusion, the Optia is tolerable, and has no significant inferiority in the yield or adverse events in apheresis collection of PBSPCs compared with Spectra-Auto. This trial was registered at http://www.umin.ac.jp/ctr/index.htm as #UMIN000012095. DisclosuresOhto:Terumo BCT: Research Funding.