The efficacy of therapeutic granulocyte transfusions is limited by the rela-tively small number of cells obtained using standard apheresis techniques. To define a mobilization schedule that maximizes cell yields while minimizing donor discomfort, we studied three donor mobilization schedules. Donors received either dexamethasone (dexa) 8 mg orally 12 hours prior to donation, granulocyte colony-stimulating factor (G-CSF) 5 mg/kg SQ 16-24 hrs prior to apheresis, or dexa plus G- CSF (D+G) in the same doses. Seven liters of whole blood were processed on the CS-3000 Plus device using Hetastarch as the sedimenting agent. Administration of G-CSF alone or the combination of dexa plus G-CSF resulted in 2.3- and 3.5-fold increases in granulocyte content in the product compared to dexa alone (from 2.09 + 0.68 with dexa alone to 4.87 + 1.02 and 7.31 + 1.56 x10 to the 10th power cells total with G- CSF and D+G, respectively) (p<0.01 for dexa vs. G-CSF alone or D+G). Addition of dexa to G-CSF resulted in a 49 percent increase in product granulocyte content compared to G-CSF alone. 72 percent of donors getting D+G had had bone pain, headache, insomnia, or fatigue. Ten percent of donors requested discontinuation of participation in the study due to the inconvenience and discomfort of the mobilization regimen. Thirty Clinical Center patients have received G-CSF mobilized granulocytes. Twenty were profoundly neutropenic, including eight patients with severe aplastic anemia, six stem cell transplant recipients, five patients with lymphoma, and one with breast cancer. The remaining ten patients had chronic granulomatous disease (CGD). In the neutropenic patients, 12 had systemic filamentous fungal infections, one had candidemia, six had bac-terial infections, and one had RSV. The mean increment in granulocyte count one hour posttransfusion was 2600/mL, and counts above 500/mL were sustained for 12 to 24 hours. Of the patients with tissue molds, seven of 12 stabilized or improved during granulocyte transfusion therapy, but only one of 12 survived hospitalization. In contrast, 3 of 6 with bacterial processes were discharged from hospital. Of ten patients with CGD, nine had complete resolution of their fungal (n=5) or bacterial (n=5) infections; the one patient who expired had extensive tissue mold. These pilot studies of G-CSF mobilized granulocytes suggest that they may confer survival benefit in carefully selected neutropenic patients with life-threatening infections. A randomized prospective study of the efficacy of G-CSF mobilized granulocyte transfusions in patients with severe aplastic anemia hospitalized at the Clinical Center is being designed to answer this question.
| 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 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; Yau, Y Y; Oblitas, J et al. (2001) Administration of G--CSF plus dexamethasone produces greater granulocyte concentrate yields while causing no more donor toxicity than G--CSF alone. Transfusion 41:1037-44 |
| Lightfoot, T; Leitman, S F; Stroncek, D F (2000) Storage of G-CSF-mobilized granulocyte concentrates. Transfusion 40:1104-10 |
