A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment

Abstract

We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains.

Advances in the treatment of acute graft‐versus‐host disease

“…In a retrospective, 5-year survival in those patients response to steroid was significantly higher than those non-response to steroid (51% versus 32%). Similar result was also reported by Martin et al [84,85]. Unfortunately, onlỹ 60% of acute GVHD patients respond to systemic steroids and many of these responses are not durable [82,86,87].…”

Diagnosis and management of acute graft‐versus‐host disease

“…Their effect is likely to be due to lympholytic effects and anti-inflammatory properties (Deeg, 2007). Two early studies assessed response to corticosteroids in patients with grade II-IV GvHD (Martin et al, 1990;Weisdorf et al, 1990). Martin et al (1990) reported overall complete or partial responses in 44% of patients.…”

“…Two early studies assessed response to corticosteroids in patients with grade II-IV GvHD (Martin et al, 1990;Weisdorf et al, 1990). Martin et al (1990) reported overall complete or partial responses in 44% of patients. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease.…”

Treatment of Acute Graft-versus-Host Disease in Childhood with Extracorporeal Photochemotherapy/Photopheresis: The Padova Experience

“…Moreover, the current survival at years in patients who respond to steroids is about 36% versus 17% in nonresponders (NR) [6] and it has been shown that transplantation-related mortality (TRM) is higher in steroidresistant patients [7,8].…”