Six granulocyte donors were recruited since the last annual report. To date, 117 healthy volunteers were accrued and signed informed consent as active granulocyte donors and donated a total of 347 filgrastim- and dexamethasone-stimulated or filgrastim-alone stimulated granulocyte apheresis components since protocol started. 17 components were collected since last report. Up to 8/20/19 this year, these products were administered to 2 patients with severe neutropenia or neutrophil dysfunction and life-threatening infections; 1 had chronic granulomatous disease (had polymicrobial pneumonia and died from massive hemolysis)) and 1 had patients transplanted for SAA (Invasive Aspergillus flavus nasal infection and nasal infection resolved) A median of 4 granulocyte transfusions (range 1 to 41) were administered per patient course since protocol inception, as has been true in prior years. Neither patient discontinued granulocyte courses due reactions or alloimmunization, though donors are carefully ABO- or HLA-matched, and when needed products undergo rbc sedimentation. Anticipated side effects of dexamethasone and/or filgrastim occurred in 56% of donors who reported one or more of the following: mild to moderate insomnia, nightmares, irritability and jitteriness, headache, bone or joint pain, fatigue or flushing. Severe symptoms were reported in <1% of donors but persisted for 48 hours in approximately 1/3rd of donors. 14 donors underwent comprehensive eye exams for cataract detection as an assessment prior to repetitive dexamethasone administration with no PSC detected. Donor retention in the program was 55%, with donor loss due to moving away from the Bethesda area or loss of interest. A mean of 6.62 liters were processed per procedure, during which 6.6 x 1010 granulocytes (range 1.04-13.14 x 1010) were collected in a volume of 356 mL. Granulocyte collection efficiency was 46.8% using the Spectra Optia apheresis device, with WBC differential composed of 87% granulocytes, and with a mean hematocrit of 4.7% and a mean red cell content of 17 mL. Two protocol amendment were ongoing. (1) 78 subjects have consented to Evaluation of bone mineral density in granulocyte donors and (2) 114 subjects have consented to Assessment of renal function in granulocyte donors. Data analysis shows that granulocyte donor bone mineral density was what would be expected for normal age and body size, that is, not diminished by repeated dexamethasone doses given before donations. Thus far, for renal function assessment, it appears that after adjusting for the confounders of age, HTN, and number of apheresis procedures, an increasing number of lifetime donations, each requiring 500cc (30 grams) of hydroxyeythyl (HES), total lifetime HES dose had no significant effect on eGFR as measured by serum creatinine in men or women. However, it appears that there is a slight, likely clinically unimportant but statistically significant, decrease in eGFR in males as measured by Cystatin C, which was not seen in females. A manuscript is in progress. All granulocyte donors are now screened and excluded for renal impairment before all donations.
