Therapeutic Efficacy Of Granulocyte Colony-stimulating F

点击翻译按钮获取中文摘要

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 (dexa) 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 x 10e10 cells with dexamethasone alone versus 4.87 and 7.31 x 10e10 cells total with G-CSF and G-CSF plus dexa, respectively) (p less than 0.01 for dexa vs G-CSF alone or G-CSF plus dexa). Seventy-two 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. Forty-nine Clinical Center patients have received G-CSF mobilized granulocytes. Thirty were profoundly neutropenic, including 13 patients with severe aplastic anemia (SAA), 10 stem cell transplant recipients, 6 patients with lymphoma, and 1 with breast cancer. The remaining 19 patients had CGD. In the neutropenic patients, 19 had systemic filamentous fungal infections, 9 had bacterial infections, and one each had RSV or candidemia. 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 13 SAA patients, versus one of 19 CGD patients. Of the neutropenic patients with tissue molds, 9 of 19 stabilized or improved during granulocyte transfusion therapy, but only 4 of 19 survived hospitalization. In contrast, three of 9 with bacterial processes were discharged from hospital. Sixteen of 19 patients with CGD had complete resolution of their fungal (8 of 11) or bacterial (8 of 8) 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 considered to further delineate the benefit to risk profile of this therapy.