Steroid refractory graft versus host disease

Abstract: Despite current standard preventive strategies that include optimizing donor selection and the combination of methorexate and a calcineurine inhibitor, acute and chronic GVHD remains a major barrier to successful hematopoietic cell transplantation for a sizeable proportion of patients. When acute and chronic GVHD become manifest a standard primary therapy approach has been the addition of glucocorticoid therapy to a background of calcineurine inhibition. When this approach fails patients with GVHD require secondary therapy. Ideally, second-line agents should promote transplantation tolerance so that the morbidity associated with prolonged use of glucocorticoids and other immunosuppressive agents can be minimized. Promising new agents or strategies which warrant further controlled clinical trials include: mycophenolate mofetil, sirolimus, humanized or chimeric monoclonal antibodies such as visilizumab, daclizumab and infliximab, and extracorporeal photopheresis. Co-operative studies are necessary to hasten the process of evaluating novel treatment strategies for acute and chronic GVHD.

The effect of ATGAM when administered in conjunction with standard therapy at the time of diagnosis of the first rejection episode was studied under two different protocols with cadaveric and living related renal transplant patients. The results from these studies demonstrate the efficacy associated with the addition of ATGAM to standard therapy for treatment of the first rejection episode in renal allograft recipients. In Study 1, a randomized controlled, two center trial of ATGAM use for treatment of acute rejection in cadaveric renal transplant patients, the addition of ATGAM to standard rejection therapy (methylprednisolone sodium succinate) resulted in an increased frequency of resolution of the first acute rejection episode which was statistically significant (p < ). ATGAM-treated patients achieved a rejection resolution rate of 80% (36/45) compared with 54% (25/46) in the control group. There was a statistically significant improvement in functional graft survival favoring the ATGAM group (p < ), and a statistically significant steroid sparing effect during the first rejection episode among patients in the ATGAM group. There was no difference in the patient survival rate between the two treatment groups. Study 2 was a randomized controlled trial conducted at five different transplant centers. In this study, the addition of ATGAM to standard rejection therapy (bolus doses of Solu-Medrol® for treatment of acute rejection in recipients of living related renal transplants resulted in an increased frequency of rejection resolution and improvement in functional graft survival. Due to the small sample size, the difference between the ATGAM group and the control group in functional graft survival rate did not achieve statistical significance. Marginal statistical significance was demonstrated in rejection reversal rate and intravenous steroid sparing among ATGAM patients (p= and p=). Patient survival rates were similar in the two treatment groups.

Steroid refractory graft versus host disease

steroid refractory graft versus host disease

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steroid refractory graft versus host diseasesteroid refractory graft versus host diseasesteroid refractory graft versus host diseasesteroid refractory graft versus host diseasesteroid refractory graft versus host disease

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