Cytokine expression in human cutaneous chronic graft-versus-host disease.

Although chronic graft-versus-host disease (GVHD) remains a frequent complication of bone marrow transplantation (BMT), the pathogenesis remains unclear. We examined the potential role of cytokines in mediating chronic GVHD. Skin samples from seven patients with cutaneous chronic GVHD, six post-BMT controls and six normal controls were evaluated by reverse transcription polymerase chain reaction for the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha), Th1-associated cytokines IL-2 and interferon-gamma (IFN-gamma), Th2-associated cytokines IL-4, IL-5 and IL-10, and fibrosis-associated cytokines platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). IFN-gamma transcription was significantly more frequent in cutaneous chronic GVHD (86%) vs post-BMT and normal controls (17% (P = 0.03) and 0 (P = 0.005), respectively). IL-2 transcription was more frequent in chronic GVHD (28%) and post-BMT controls (50%) vs normal controls (17%). TNF-alpha mRNA was frequent in chronic GVHD (71%) and post-BMT controls (83%), but not significantly more than in normal controls (50%). Transcription of IL-1alpha, IL-4, IL-5 and IL-10 was infrequent in all three groups. PDGF and TGF-beta mRNA were detected in the majority of all samples. The frequent transcription of IFN-gamma in cutaneous chronic GVHD supports its potential role in mediating the associated tissue injury. While the cellular sources of these cytokines are uncertain, their expression and secretion in situ may propagate the cytotoxic cascade and perpetuate the tissue injury. Better understanding of the contribution of FN-gamma and other cytokines to the pathogenesis of chronic GVHD may allow the design of more specific and more effective therapy.

Predictive factors for chronic graft-versus-host disease after histocompatible sibling donor bone marrow transplantation.

We analyzed factors associated with the development of chronic graft-versus-host disease (GVHD) in 469 consecutive patients receiving matched sibling allogeneic bone marrow transplantation (BMT). Overall, 41 +/- 6% (95% confidence interval) developed chronic GVHD between 2 and 50 months after BMT. Multivariate analysis showed that previous acute GVHD was the dominant independent risk factor predisposing to chronic GVHD (Relative Risk 4.82, p < 0.0001). In addition, recipient age of > or = 18 years and male recipient with female donor were also independent predictive factors for development of chronic GVHD. When acute GVHD and recipient age were considered, groups with distinctive risks of chronic GVHD were identified. Patients under 18 without previous grade II-IV acute GVHD had only a 10 +/- 5% risk of chronic GVHD. Patients over 18 with no prior grade II-IV acute GVHD had a 31 +/- 12% risk while patients with advanced acute GVHD, regardless of age, had the highest risk and 70 +/- 8% developed chronic GVHD. It is important to consider these factors when designing and assessing clinical trials of chronic GVHD prophylaxis and treatment.