Gran study One granulocyte donor was recruited since the last annual report. To date, 69 healthy volunteers were accrued as active granulocyte donors and donated a total of 175 filgrastim- and dexamethasone-stimulated or filgrastim-alone stimulated granulocyte apheresis components since protocol started. Fourteen components were collected since last report. Up to 8/31/15 this year , these products were administered to 3 patients with severe neutropenia or neutrophil dysfunction and life-threatening infections; one recipient had severe aplastic anemia, and two had chronic granulomatous disease. In total, eleven of 28 recipients had disseminated mold and 17 had life-threatening bacterial infections, including two with carbapenem-resistant Klebsiella pneumonia. A median of 4 granulocyte transfusions (range 1 to 41) were administered per patient course. Five patients did not respond to the granulocyte transfusions (GTX) and died rapidly, one assessed as a futile effort, and the other unable to receive a sustained course of GTX due to HLA alloimmunization and lack of compatible donors. The remaining 23 showed stability or clinical improvement, although 7 later died due to their underlying disease. Seventeen of 28 were discharged from hospital. One recipient developed HLA alloimmunization due to GTX, which resulted in rejection of an unrelated cord blood graft. Donors experienced mild to moderate insomnia, nightmares, irritability and jitteriness related to the dexamethasone, and myalgia, arthralgias, fatigue and flushing related to the filgrastim administration. Thirty donors underwent comprehensive eye exams for cataract detection as a baseline assessment prior to repetitive dexamethasone administration. Donor retention in the program was 78%, with donor loss due to moving away from the Bethesda area or loss of interest. A mean of 7.3 liters were processed per procedure, during which 6.61 x 10e10 granulocytes (range 4.08-9.13 x 10e10) were collected in a volume of 338 mL. Granulocyte collection efficiency was only 42% using the Spectra apheresis device, with WBC differential composed of 90% granulocytes, and with a mean hematocrit of 10.6% and a mean red cell content of 36 mL.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACL002124-04
Application #
9154066
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
Zip Code
Tholpady, Ashok; Chiosea, Ion; Lyons, Jonathan J et al. (2013) Systemic hypersensitivity reaction mimicking anaphylaxis after first filgrastim administration in a healthy donor. Transfusion 53:1146-7
O'Donghaile, Diarmaid; Childs, Richard W; Leitman, Susan F (2012) Blood consult: granulocyte transfusions to treat invasive aspergillosis in a patient with severe aplastic anemia awaiting mismatched hematopoietic progenitor cell transplantation. Blood 119:1353-5
Olnes, Matthew J; Poon, Andrea; Miranda, Susan J et al. (2012) Effects of granulocyte-colony-stimulating factor on Monosomy 7 aneuploidy in healthy hematopoietic stem cell and granulocyte donors. Transfusion 52:537-41
Strauss, R G; Klein, H G; Leitman, S F et al. (2011) Preparation of granulocyte concentrates by apheresis: collection modalities in the USA. Vox Sang 100:426-33
Heim, K F; Fleisher, T A; Stroncek, D F et al. (2011) The relationship between alloimmunization and posttransfusion granulocyte survival: experience in a chronic granulomatous disease cohort. Transfusion 51:1154-62
Clayton, Janine A; Vitale, Susan; Kim, Jonghyeon et al. (2011) Prevalence of posterior subcapsular cataracts in volunteer cytapheresis donors. Transfusion 51:921-8