Safety and efficacy of granulocyte colony-stimulating factor in kidney and liver transplant recipients

Background: Leukopenia is not infrequently encountered following solid organ transplantation, most often in the setting of cytomegalovirus (CMV) disease and/or its treatment with ganciclovir. The present study was undertaken to determine the safety and efficacy of granulocyte colony‐stimulating factor (G‐CSF) in renal and liver transplant recipients with leukopenia. Methods: Between 1 June 1991 and 1 June 1998, patients received G‐CSF for 2 indications: 1) white blood cell count (WBC) <3000/mm³, with a decline from baseline; 2) to shorten the duration of leukopenia associated with chemotherapy. A retrospective review of the outcome of such therapy was undertaken. Results: 50 patients were given 100 courses of treatment with G‐CSF; 35 of 168 liver transplant recipients (20.8%), 14 of 391 kidney transplant recipients (3.6%), and 1 of 4 recipients of combined liver–kidney transplants (25.0%) received from 1 to 9 courses of G‐CSF. Presumed causes of leukopenia were identified as ganciclovir in 28 cases (28.0%), CMV in 21 (21.0%), chemotherapy in 12 (12.0%), sepsis in 11 (11.0%), azathioprine in 5 (5.0%), interferon in 3 (3.0%) and other causes in 20 cases (20.0%). The median length of therapy was 10.0 days (range 1–154 days) and the average dose of daily G‐CSF received was 3.9±1.5 μg/kg/day. The average WBC was (2.4±1.3)×10³/μl at the beginning of therapy, and (13.8±9.1)×10³/μl at the end of therapy. In 7 of 100 treatments (7.0%) a WBC of 5.0×10³/μl was not reached during G‐CSF therapy; in 6 of these 7 cases, G‐CSF therapy lasted fewer than 4 days. The mean time needed to reach a WBC count of 5×10³/μl was 3.7±3.3 days among 71 patients who had daily WBC counts sent. Eight G‐CSF treatments (8.0%) were followed by episodes of rejection appearing during or within 2 months of treatment; 5 of them were biopsy‐documented. No relation was found between the highest WBC obtained during G‐CSF therapy and the risk of rejection. Eight patients (16.0%) died while receiving G‐CSF, all from infection. Six of these 8 patients were receiving G‐CSF for leukopenia secondary to sepsis. Overall, 25 patients (50.0%) received 49 courses of G‐CSF secondary to CMV and/or ganciclovir therapy. In 40 of 49 courses (81.6%), ganciclovir could be continued at recommended doses. Twenty‐one of 22 patients (95.5%) with symptomatic CMV infection had a clinical response to ganciclovir. Sixteen of 18 patients (88.9%) treated for a CMV infection and followed with serial antigenemia assays attained microbiological cure; both patients who did not were infected with ganciclovir resistant CMV. Conclusion: G‐CSF was well tolerated in solid organ transplant recipients. It was particularly useful in patients with CMV disease, allowing optimal ganciclovir therapy ( Note Presented in part at the American Society of Transplant Physicians Meeting, Chicago, Illinois, May 1999.
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