Chronic graft-versus-host disease: clinical manifestation and therapy

Abstract

Summary:Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in long-term survivors of allogeneic stem cell transplantation. The immunopathogenesis of chronic GVHD is, in part, TH-2 mediated, resulting in a syndrome of immunodeficiency and an autoimmune disorder. The most important risk factor for chronic GVHD is prior history of acute GVHD and strategies that prevent acute GVHD also decrease the risk of chronic GVHD. Other important risk factors are the use of a non-T cell-depleted graft, and older age of donor and recipient. Whether recipients of peripheral blood stem cells are at increased risk of chronic GVHD remains unsettled. There are no known pharmacologic agents which can specifically prevent development of chronic GVHD. Agents which have efficacy in the treatment of autoimmune disorders have been utilized as therapy for established chronic GVHD and are associated with response rates of 20% to 80%. Most responses are confined to skin, soft tissue, oral mucosa and occasionally liver. Bronchiolitis obliterans responds infrequently to therapy and is associated with a dismal prognosis. Newer, promising therapeutic strategies under investigation include thalidomide, photopheresis therapy, anti-tumor necrosis factor and B cell depletion with anti-CD20 monoclonal antibody. Bone Marrow Transplantation (2001) 28, 121-129.

Graft‐versus‐host disease (GVHD)‐specific survival and duration of systemic immunosuppressive treatment in patients who developed chronic GVHD following allogeneic haematopoietic cell transplantation

“…Hepatic dysfunction is not a common cause of death in chronic GVHD (Ratanatharathorn et al, 2001) and only one patient died of hepatic failure related to GVHD in our study. However, increased levels of serum bilirubin and alkaline phosphatase were independent risk factors for GSS in our study.…”

Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation

“…Although the pathogenesis of GVHD is not clearly understood, it is believed that donor T lymphocytes play an important role in its acute and chronic phases with the predominance of T H 2 cytokines such as IL-4, IL-5, and IL-13 in the chronic phase. 16 Various studies have shown a strong association between fibrogenesis, a hallmark of PTCB, and the development of a T H 2 CD4 inflammatory response that involves IL-4 and IL-13. [17][18][19][20] Given the fact that PTCB is a form of chronic GVHD of the lung it is plausible that it is a T H 2-mediated disease, which may explain the clinical response we observed to inhaled corticosteroids.…”

Optimal management of chronic graft‐versus‐host disease in children

“…Patients with BO typically present with a cough or dyspnea (Ratanatharathorn et al, 2001). Every attempt should be made to have children perform PFTs, which can usually be done by children as young as 5 or 6 years of age.…”