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) and dexamethasone (dexa) stimulation of the donor contained 3.5-fold greater numbers of granulocytes than products prepared using dexamethasone alone (product content 2.09 x 10e10 cells with dexamethasone alone versus 7.31 x 10e10 cells total with G-CSF plus dexa, p less than 0.01 for dexa vs G-CSF plus dexa). Seventy-five percent of donors getting G-CSF plus dexa 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. Seventy-nine Clinical Center patients have received G-CSF mobilized granulocytes. Fifty-six were profoundly neutropenic, including 25 patients with severe aplastic anemia (SAA), 17 stem cell transplant recipients, 12 patients with lymphoma/leukemia, and 1 each with breast cancer and melanoma. The remaining 22 patients had CGD or leukocyte adhesion deficiency (LAD). In the neutropenic patients, 34 had systemic filamentous fungal infections, 19 had bacterial infections, two had candidemia and one had RSV infection. 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. Two of the 21 neutropenic, immunosuppressed patients who survived longer than 2 weeks after the initiation of granulocyte transfusions developed HLA allosensitization, as did two of the 15 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 21 SAA patients, versus one of 21 CGD patients. Of the neutropenic patients with tissue molds, 14 of 34 stabilized or improved during granulocyte transfusion therapy, but only 10 of 34 survived hospitalization. In contrast, nine of 19 with bacterial processes were discharged from hospital. Nineteen of 22 patients with CGD had resolution of their fungal (10 of 13) or bacterial (9 of 9) infections. In two patients with LAD and large non-healing cutaneous ulcers, topical application of starch sedimented granulocytes three times weekly was associated with healing and closure of the skin lesions. 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 prospective multicenter study of the efficacy and feasibility of G-CSF mobilized granulocyte transfusions in severely neutropenic patients with filamentous fungal infections is being organized by the Hemostasis/Transfusion Medicine Clinical Trials Network of NHLBI.
| 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 |
