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 microg/kg/day. The average WBC was (2.4+/-1.3 )x 10(3)/microl at the beginning of therapy, and (13.8+/-9.1) x 10(3)/microl at the end of therapy. In 7 of 100 treatments (7.0%) a WBC of 5.0 x 10(3)/microl 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 x 10(3)/microl 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.


CONCLUSIONS
G-CSF was well tolerated in solid organ transplant recipients. It was particularly useful in patients with CMV disease, allowing optimal ganciclovir therapy.
Turgeon
N
N
Transplantation Unit, Massachusetts General Hospital, Boston, Massachusetts 02114-2696, USA.
Hovingh
G K
GK
Fishman
J A
JA
Basgoz
N
N
Tolkoff-Rubin
N E
NE
Doran
M
M
Cosimi
A B
AB
Rubin
R H
RH
D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D007958:Leukocyte Count; D007970:Leukopenia / Q000188:drug therapy* / Q000209:etiology; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012189:Retrospective Studies; D012449:Safety; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D015774:Ganciclovir