The Use of Granulocyte Colony-Stimulating Factor After Liver Transplantation

Foster, Patricia L.; Mital, Deepak; Sankary, Howard; McChesney, Lawrence; Marcon, Joanne; Koukoulis, George Κ.; Kociss, Kent; Leurgans, Sue; Whiting, James F.; Williams, James W.

doi:10.1097/00007890-199506000-00009

Cited by 47 publications

(19 citation statements)

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“…The secondary immunological effects might, however, be doseor schedule-dependent. For example, in liver transplant recipients, a short course of high-dose G-CSF was associated with a reduction in the incidence of acute rejection, 34 while a 21-day course of low-dose G-CSF resulted in an increase in biopsy-proved rejection. 35 Other variables that may have confounded the analysis include the type of GVHD prophylaxis, use of T-cell depletion, the degree on histoincompatibility between patient and donor, and whether the cytokine was glycosylated.…”

Section: Discussionmentioning

confidence: 99%

The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis

Mirza²,

Junco

et al. 2003

Bone Marrow Transplant

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Summary:The effect of hematopoietic growth factors on neutrophil recovery after allogeneic transplantation is well-recognized. Recent laboratory studies demonstrated that these cytokines may also modify T-cell and dendritic cell function, but whether the effect is strong enough to alter the risk of GVHD is unclear. We performed a metaanalysis to determine the effect of G-CSF or GM-CSF on the risk of nonhematopoietic outcomes after allogeneic transplantation. A search of the literature from 1986 to present yielded 18 publications in which data were provided for cohorts receiving growth factor vs either placebo or no therapy. These included nine prospective randomized studies, eight retrospective cohort studies, and one case-control study comprising a total of 1198 patients. The publication types were heterogeneous with regard to demographic and treatment characteristics, although within publications, comparative groups were generally balanced. The pooled risk ratio estimates with use of growth factor was 1.08 (95% CI 0.87-1.33, P ¼ 0.48) for grades 2-4 acute GVHD, 1.22 (95% CI 0.80-1.86, P ¼ 0.99) for grades 3-4 acute GVHD, and 1.02 (95% CI 0.82-1.26, P ¼ 0.87) for chronic GVHD. This analysis did not detect a significant change in the risk of acute or chronic GVHD after allogeneic hematopoietic stem cell transplantation when hematopoietic growth factors were used to shorten the initial period of neutropenia. Bone Marrow Transplantation (2003) 32, 771-775. doi:10.1038/sj.bmt.1704228 Keywords: graft-vs-host disease; G-CSF; GM-CSF; allogeneic G-CSF and GM-CSF are hematopoietic cytokines active in the differentiation and proliferation of neutrophil progenitors as well as the regulation of mature neutrophil activity.Prospective clinical trials and retrospective cohort studies examining the safety and efficacy of these cytokines following allogeneic hematopoietic stem cell transplantation have variably demonstrated several beneficial effects, including reductions in time to hematopoietic recovery, transplant-related toxicity, duration of initial hospitalization, and resource utilization. As a result, judicious use of such growth factors is now considered routine at many allogeneic transplant centers.The understanding of the secondary effects of G-CSF and GM-CSF, especially on the immune system, continues to evolve. In vitro studies of peripheral blood from healthy volunteers showed a Th2 polarization and anti-inflammatory profile in those treated with G-CSF, 23 while GM-CSF induced a profound proinflammatory response, 24 suggesting that when used for acceleration of neutrophil recovery after allogeneic transplantation, these cytokines might alter the risk of GVHD. Since most individual studies of cytokines for engraftment are not powered sufficiently to test for effects on GVHD, we performed a meta-analysis of the published data to determine whether the use of G-CSF and GM-CSF after allogeneic transplantation altered early nonhematopoietic outcomes. Methods Identification of studies and data abstractionA Medline searc...

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Section: Discussionmentioning

confidence: 99%

The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis

Mirza²,

Junco

et al. 2003

Bone Marrow Transplant

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“…23 Other strategies such as surveillance culturing or the prophylactic administration of granulocyte colony-stimulating factor may also help ameliorate morbidity from infections. 24 In summary, OKT3 induction immunosuppression after liver transplantation is associated with a manageable incidence of bacterial, viral, and fungal infections. Aggressive antimicrobial prophylaxis is important in this setting.…”

Section: Discussionmentioning

confidence: 99%

Infectious complications after OKT3 induction in liver transplantation

1997

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The present study examines the incidence, risk factors, bacteriology, and mortality of infectious episodes and the role of antimicrobial prophylactic regimens after OKT3 induction in liver transplantation. Infections occurring in the first 6 months were evaluated according to the Centers for Disease Control criteria in 102 transplant recipients. Patients were administered OKT3 for 5 to 10 days, beginning intraoperatively, azathioprine, low-dose prednisone, and delayed introduction of cyclosporine. There were 140 major and 30 minor infections for an incidence of 1.7 infections per patient. Twenty-seven patients (26%) had no infectious episodes during the 6 months of followup. Bacterial and fungal infections peaked during the first month posttransplantation, whereas viral infections peaked during the second month. Infection-related mortality was 10%. One-year survival rate of patients who suffered a major infection was less than those who were infection free, but the difference was not statistically significant (79% vs. 89%; P ‫؍‬ .61). There was a significantly higher incidence of enterococcal infections under cefotetan prophylaxis than under ampicillinsulbactam (.375 vs. 11 infections per patient; P ‫؍‬ .0017). There were 14 episodes of cytomegalovirus disease (14%) but no cytomegalovirusrelated mortality or graft loss, and all cases responded to ganciclovir treatment. Bivariate and multivariate analyses identified only retransplantation as a risk factor for infection. In conclusion, OKT3 induction after liver transplantation is associated with a manageable incidence of bacterial, viral, or fungal infections. This is caused by, at least in part, improved anti-infective prophylaxis. Copyright 1997 by the American Association for the Study of Liver Diseases I t has been a central tenet in transplantation that any therapy that decreases the likelihood of acute rejection is likely to be accompanied by a corresponding increase in the likelihood of infection. A prime example of this paradigm has been the use of the monoclonal antibody OKT3 to treat steroid-resistant rejection. Although extraordinarily effective in reversing established rejections, the use of OKT3 in these circumstances has been accompanied by an increase in the prevalence of infections, especially those of viral etiology. 1 In contrast, small, randomized comparative studies of OKT3 as induction immunotherapy vs. cyclosporine therapy have not documented an increase in infections with the use of OKT3 in this setting but have shown immunologic advantages such as a 20%-40% decrease in the incidence of acute rejection. 2-5 A detailed examination of infections in liver transplant recipients receiving OKT3 induction has not been published. Therefore, we reviewed an unselected cohort of 102 patients undergoing primary orthotopic liver transplantation to determine the incidence of bacterial, fungal, and viral infections after OKT3 induction, including type, frequency, and risk factors of infections as well as the impact of antimicrobial prophylaxis on the infe...

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“…With recognition of the common basis for bone marrow transplantation and organ acceptance (chimerism), therapy with these molecules could become an adjunct to, or even a substitute for, the leukocyte augmentation in whole organ recipients currently under trial (142). For example, we suspect that increased chimerism explains the significant improvement in BN ...... LEW heart allograft survival described by Foster et al in animals treated postoperatively with G-CSF (143). Conversely, Monaco et al (144) have described improved tolerance induction using donor bone marrow pretreated vvith GM-CSF.…”

Section: Discussionmentioning

confidence: 99%