Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome

Abstract

We have analyzed the long term outcome of 197 patients who were treated for grade II to IV acute graft-versus-host disease (GVHD) following histocompatible allogeneic bone marrow transplantation (BMT). Of 469 recipients of sibling donor allografts performed at our center between January, 1979 and October, 1987, 197 patients (42%) developed greater than or equal to grade II acute GVHD at a median of 38 days (range 9 to 98 days) post-BMT. After treatment with corticosteroids (n = 160) or other immunosuppressive therapies (n = 37), 72 patients (41% +/- 8%; 95% confidence interval [CI]) achieved complete and continuing resolution of acute GVHD after a median of 21 days of therapy. Sixty- one patients required additional immunosuppressive therapy with high dose methylprednisolone, antithymocyte globulin (ATG)/steroids, or other therapies because of refractory or progressive symptoms of acute GVHD. Seven of these 61 patients eventually obtained complete and continuing remission after 13 to 57 days (median 50) of secondary treatment. The overall rate of chronic GVHD was 70% +/- 16%; 95% CI following grade II to IV acute GVHD. Twenty-five of the 197 patients never developed chronic GVHD, resulting in a Kaplan-Meier projection of 30% +/- 8% (95% CI) cure of moderate/severe acute GVHD. Analysis of clinical features associated with complete response (CR) to acute GVHD therapy identified more favorable responses to therapy in patients without either liver or skin involvement, patients with acute lymphoblastic leukemia, and donor/recipient pairs other than male patients with female donors. Older recipient age was not associated with more resistance to GVHD treatment. CR to GVHD treatment was associated with significantly better 5-year survival: 51% +/- 14% versus 32% +/- 11% for patients with therapy resistant acute GVHD (P = .004). GVHD was a major contributing cause of death in 49 of the 90 patients who died and was often complicated by infection or interstitial pneumonitis. Control of acute GVHD through immunosuppressive therapy did not affect the risk of leukemic relapse after transplantation.

Combination therapy with tacrolimus and anti‐thymocyte globulin for the treatment of steroid‐resistant acute graft‐versus‐host disease developing during cyclosporine prophylaxis

“…The outcome data from our report of tacrolimus and ATGAM therapy suggests superior response rates and survival than either agent alone. It also compares favourably with published data on the prognosis of GVHD after secondary therapy in which outcome is very poor (Deeg & Henslee-Downey, 1990;Weisdorf et al, 1990;Martin et al, 1991;Pavletic et al, 1999). Reports of newer monoclonal antibodies in the management of steroid refractory acute GVHD also detail promising response rates warranting further investigation (Heslop et al, 1995;Przepiorka et al, 2000).…”

“…Preventative strategies with immunosuppressive agents have been extensively studied in randomized trials, with the combination of cyclosporine and short-course methotrexate being adopted as a common standard care (Storb et al, 1986(Storb et al, , 1989(Storb et al, , 1992Ringden et al, 1993). When acute GVHD occurs, high-dose glucocorticosteroids are the mainstay of treatment (Martin et al, 1990Weisdorf et al, 1990), with failure to respond associated with a very poor prognosis. Intensification of immunosuppression with anti-thymocyte globulin (ATGAM), monoclonal anti-T-cell antibodies, and anti-cytokine or anti-cytokine receptor monoclonal antibodies is an alternative option (Doney et al, 1981;Roy et al, 1992;Anasetti et al, 1994;Antin et al, 1994;Herbelin et al, 1994;Hebart et al, 1995).…”

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].…”

What predicts high risk acute graft‐versus‐host disease (GVHD) at onset?: identification of those at highest risk by a novel acuteGVHDrisk score

“…Despite many advances in haematopoietic cell transplantation (HCT), acute graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality. Corticosteroids are the conventional first-line systemic therapy, but only 1/2 of patients will respond and only 1/3 will have a durable response (Weisdorf et al, 1990a;MacMillan et al, 2002a). It is well established that patients with severe (clinical grade III-IV) acute GVHD are less responsive to steroids leading to poor survival and high transplant-related mortality (TRM).…”