Granulocyte colony-stimulating factor (G-CSF) is the standard growth factor for mobilizing hematopoietic progenitor cells in healthy peripheral blood progenitor cell (PBPC) donors. G-CSF is given daily for 5 days to PBPC donors prior collecting (PBPC) concentrates by apheresis. PBPC concentrate donors given G-CSF experience splenic enlargement and rarely, spontaneous rupture of the spleen. We evaluated the incidence and time course of splenic enlargement in PBPC concentrate donors and accessed factors effecting size changes. Healthy adults were given G-CSF (10 micrograms/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length prior to giving G-CSF, the day of apheresis, and 4 days after apheresis. Spleen length increased in 19 of 20 donors. On the day of apheresis the average length was 14% greater than before G-CSF and 4 days after PBPCs were collected spleen length was reduced in length, but remained greater than baseline levels. A second study was initiated to determine if spleen length returns to baseline levels 10 days after apheresis. Healthy adults were again given G-CSF (10 micrograms/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length prior to giving G-CSF, the day of apheresis, and 10 days after apheresis. Spleen length increased in 9 of 10 donors. Mean spleen length changed from 10.7 ? 1.1 cm pre-G-CSF to 12.0 ? 0.8 cm on the apheresis day. The mean increase in length was 1.4 ? 1.0 cm or 13.6 ? 10.9%. 10 days after apheresis the spleen length fell to 10.7 ? 1.1 cm and did not differ from baseline levels. For 8 of the 9 donors whose spleen length increased, the length measured 10 days after apheresis was within 0.5 cm of baseline length. In one donor spleen length remained 0.7 cm or 7% longer than baseline length 10 days after apheresis. This donor was a 23-year old Caucasian female whose spleen length on the apheresis day was 1.9 cm or 18% longer than baseline length. We found that spleen length increases in PBPC donors are transient and reversible. In most donors the spleen returned to normal size within 10 days. Future studies will focus on studying the use of a new long-acting form of G-CSF, polyethylene glycolated-G-CSF (PEG-G-CSF) to mobilized PBPCs in healthy donors. The optimum dose and safety of PEG-G-CSF will be studied.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL002099-05
Application #
6825268
Study Section
(DTM)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Jin, Ping; Wang, Ena; Ren, Jiaqiang et al. (2008) Differentiation of two types of mobilized peripheral blood stem cells by microRNA and cDNA expression analysis. J Transl Med 6:39
Ren, Jiaqiang; Jin, Ping; Wang, Ena et al. (2007) Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation. J Transl Med 5:1
Stroncek, David F; Jin, Ping; Wang, Ena et al. (2007) Potency analysis of cellular therapies: the emerging role of molecular assays. J Transl Med 5:24
Stroncek, David; Slezak, Stefanie; Khuu, Hanh et al. (2005) Proteomic signature of myeloproliferation and neutrophilia: analysis of serum and plasma from healthy subjects given granulocyte colony-stimulating factor. Exp Hematol 33:1109-17
Stroncek, David; Dittmar, Kristin; Shawker, Thomas et al. (2004) Transient spleen enlargement in peripheral blood progenitor cell donors given G-CSF. J Transl Med 2:25
Stroncek, David; Shawker, Thomas; Follmann, Dean et al. (2003) G-CSF-induced spleen size changes in peripheral blood progenitor cell donors. Transfusion 43:609-13
Stroncek, David F; Matthews, Cynthia L; Follmann, Dean et al. (2002) Kinetics of G-CSF-induced granulocyte mobilization in healthy subjects: effects of route of administration and addition of dexamethasone. Transfusion 42:597-602
Stroncek, D F; Confer, D L; Leitman, S F (2000) Peripheral blood progenitor cells for HPC transplants involving unrelated donors. Transfusion 40:731-41