The efficacy of therapeutic granulocyte transfusions is limited by the relatively small number of cells obtained using standard apheresis techniques. In prior studies, we demonstrated that granulocyte concentrates prepared by granulocyte-colony stimulating factor (G-CSF) or the combination of G-CSF and dexamethasone stimulation of the donor contained 2.3- and 3.5-fold greater numbers of granulocytes than products prepared using dexamethasone alone (product content 2.09 plus or minus 0.68 x 10 to the tenth power cells with dexamethasone alone versus 4.87 plus or minus 1.02 and 7.31 plus or minus 1.56 x 10 to the tenth power cells total with G-CSF and G-CSF plus dexamethasone, respectively) (p less than 0.01 for dexa vs G-CSF alone or D+G). Seventy-two percent of donors getting dexamethasone plus G-CSF had restlessness, insomnia, bone pain, or headache. Ten percent of donors requested discontinuation of participation in the study due to the inconvenience and discomfort of the mobilization regimen. Thirty-seven Clinical Center patients have received G-CSF mobilized granulocytes. Twenty-four were profoundly neutropenic, including ten patients with severe aplastic anemia (SAA), eight stem cell transplant recipients, five patients with lymphoma, and one with breast cancer. The remaining 13 patients had CGD. In the neutropenic patients, 15 had systemic filamentous fungal infections, one had candidemia, seven had bacterial infections, and one had RSV. The mean increment in granulocyte count 1-hour post-transfusion was 2600/uL, and counts greater than 500/uL above baseline were sustained for 12 to 24 hours. One of the 11 neutropenic, immunosuppressed patients who survived longer than 2 weeks after the initiation of granulocyte transfusions developed HLA allosensitization, as did two of the 13 CGD patients. In the absence of HLA allosensitization, granulocyte transfusions were associated with progressive hypoxia, pulmonary infiltrates, and an ARDS-like event in four of ten SAA patients, versus none of 13 CGD patients. Of the neutropenic patients with tissue molds, eight of 15 stabilized or improved during granulocyte transfusion therapy, but only two of 15 survived hospitalization. In contrast, three of seven with bacterial processes were discharged from hospital. Ten of 13 patients with CGD had complete resolution of their fungal (n=5) or bacterial (n=5) infections. These pilot studies of G-CSF mobilized granulocytes suggest that they may confer survival benefit in carefully selected neutropenic patients with life-threatening infections, but may be associated with significant progressive pulmonary toxicity. A randomized prospective study of the efficacy of G-CSF mobilized granulocyte transfusions in patients severe aplastic anemia hospitalized at the Clinical Center is being designed to further delineate the benefit to risk profile of this therapy.
| 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 |
