In other non-HSCT settings, BOOP has been seen in association with infection, drugs, radiation therapy, and a number of connective tissue disorders . It has also been shown that
the 2-year cumulative incidence of late-onset non-infectious pulmonary complications (LONIPC, including BO and BOOP) has been 10% in 438 patients undergoing HSCT. Moreover, the survival rate at 5 years has been significantly worse in affected subjects than in unaffected ones . Graft versus host disease (GVHD) is a frequent and lethal complication Everolimus chemical structure of HSCT that limits the use of this important C646 therapy. On the basis of pathophysiology and appearance, GVHD is classified in acute and chronic one . Acute GVHD occurs prior to day 100 after transplant and it consists in an enhanced inflammatory/immune response, mediated by the competent donor’s lymphocytes, infused into the recipient, where they react against an environment perceived as a foreign one. The process is amplified through the tissue release of molecules which stimulate the donor’s lymphocytes. This apparently contradictory phenomenon is simply a physiological
reaction Levetiracetam of the damaged tissue to the disease which has led to the transplant therapy . Acute GVHD presents clinical manifestations in the skin, i.e. maculopapular rash, which can spread throughout the body, dyskeratosis (in severe cases the skin may blister and ulcerate) , in the gastrointestinal
tract, i.e. diarrhea, emesis, anorexia, abdominal pain, mucosal ulceration with bleeding, luminal dilatation , and in the liver, i.e. same liver dysfunction of veno-occlusive disease, drug toxicity, viral infection, sepsis, or iron overload . Chronic GVHD is the major cause of late non-relapse death following HCT . However, chronic GVHD pathophysiology is not completely understood. Probably, thymus atrophy or dysfunction, which can develop after pharmacological preparation of transplant, play a major role in chronic GVHD manifestation. This fact leads to a peripheral tolerance decrease and to an increase in the number of autoreactive T lymphocytes. Autoreactive T lymphocytes lead to an interferon gamma mediated increase in the collagen deposition and fibrosis, a characteristic feature of chronic GVHD [97, 98]. The manifestations of chronic GVHD are protean and often of an autoimmune nature. Many districts are involved, i.e.