Granulocyte Donation with GCSF

Clinical Center

Investigators

Linked publications, trials & patents

Abstract

Since the last annual report, four (4) new subjects were enrolled onto the protocol, and 2 subjects withdrew from participation. To date, a total of 123 healthy volunteers have been enrolled and signed informed consent, of which 83 donors have donated G-CSF- (+/- dexamethasone) stimulated granulocytapheresis components at least once since the start of the protocol. Since the last annual report up to 8/25/2021, nineteen (19) donors donated a total of 25 products for three different recipients 12, 1, and 12, respectively. This past year, 104 donors did not donate at all, due to lack of need, scheduling conflicts, or ABO or HLA incompatibilities. Overall, donor retention in the program is 50%, with donor attrition due to moving away from the Bethesda area or loss of interest. In 28% of collection procedures, donors were stimulated with G-CSF and dexamethasone, 72% with G-CSF only. Donors reported symptoms included bone pain, irritability, fatigue, fever, chills, and nausea. These effects were expected consequences of G-CSF and/or dexamethasone administration, and are described in the protocol and the consent. All 25 granulocytapheresis products were collected using the Spectra Optia apheresis device, with an average of 6.74 liters of whole blood processed per procedure. Mean yield was 4.9 x 10e10 neutrophils (range 2.87 - 9.45 x 10e10) collected in an average volume of 408 mL. Mean product neutrophil content 84.8% of WBC, mean product hematocrit 7.78% and mean product RBC content of 34.2 mL. In 36% of collection procedures, donors were stimulated with G-CSF and dexamethasone, 64% with G-CSF only. Donors reported symptoms in 13 (59%) of procedures, and reported use of over-the-counter analgesics (NSAIDS) in 5 cases. Reported symptoms included bone pain (9, 41%), headache (3, 14%), irritability (6, 27%), fatigue (3, 14%), fever, chills, nausea (1, 4.5%). The maximum severity of symptoms was rated as mild in 36% of donations, moderate in 18% and severe in 9%. Some of these symptoms persisted with mild to moderate severity (on a subjective assessment scale of 1 to 4) 48 hours after donation in 33%; severe symptoms did not persist. These effects were expected consequences of G-CSF and/or dexamethasone administration, and are described in the protocol and the consent. Eye Exam Monitoring: Since the last annual report, 85 of 119 donors underwent 108 eye exams in total. Donors who have not had an eye exam in the last 2 years are restricted to G-CSF alone. The donors must schedule these exams in advance and often this does not occur. Of the new (7) eye exams performed this CR, no new PSCs were detected. Renal Function and Bone Density by Dexascan Substudies Progress: Since approval of Amendment (I) May 2016, 114 donors have consented to the substudies: 78 consented to both bone mineral density (BMD) dexascans and renal studies, 36 donors consented to renal studies. Thus far 78 dexascans and 114 phlebotomies (for the renal substudy) were completed. All granulocyte donors participating in the BMD study have normal Z scores by dexascan regardless of lifetime dexamethasone dose and this was presented in abstract form at a national meeting in 2019. For the renal study, 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 or 30 grams of hydroxyeythyl (HES), total 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, statistically significant, but perhaps clinically unimportant decrease in eGFR in males as measured by Cystatin C, which was not seen in females. A manuscript is in progress. Out of an abundance of caution, measurement of eGFR using serum creatinine is now required for all granulocyte donors within 2 years prior to donations, with exclusion of donors from granulocyte donation for renal impairment.