Impact of chronic GVHD on late complications after hematopoietic cell transplantation
Current results with transplantation of marrow or blood derived hemopoietic stem cells (HCT) in patients with aplastic anemia and patients who do not develop chronic graft-versus-host disease (GVHD) show life expectancies similar to agematched controls. However, patients with advanced malignant diseases and patients who develop chronic GVHD after transplant are at risk of late disease recurrence and delayed, potentially fatal complications  . Major complications associated with chronic GVHD
... with chronic GVHD are listed in Table I . Infections Late infections due to bacterial, viral and fungal organisms occur most commonly in patients with chronic GVHD. Early post-transplant prophylaxis may result in an increased incidence of late infections (see e.g., acyclovir/ganciclovir and late CMV infections). It is standard practice to give prophylaxis for infections caused by Pneumocystis carinii, varicella zoster and encapsulated bacteria (and, more recently, fungal organisms) during the first year post-transplant, or longer, for patients with chronic GVHD. Airway and pulmonary disease The bronchial tree may be involved by GVHD , and immunosuppression related to GVHD or its therapy may enhance pulmonary infection. Late onset interstitial pneumonia usually occurs in patients with chronic GVHD  . Restrictive pulmonary changes do not appear to correlate with chronic GVHD. The pathogenesis of air flow obstruction (AFO) after HCT is not fully understood , but recurrent aspirations, possibly associated with GVHD of the esophagus or purulent sinus drainage, contribute to airway inflammation and the development of obstructive lung disease. A recent study analyzed AFO in 1049 patients who received an allogeneic HCT at FHCRC  .here were 257 patients (25%) with significant AFO as defined by a decline in pFEV1 by more than 5% per year. In multivariate logistic regression analysis, patients with quiescent (relative risk [RR] 1.5, 95% CI 1.2 Á/1.7) or progressive onset (RR 2.5, 95% CI 1.4 Á/3.1) of chronic GVHD, among other factors, were at an increased risk, and those with chronic GVHD and AFO had a higher risk of mortality (hazard ratio 1.9, P 0/0.002) than patients without AFO. Thus, AFO had a significant independent effect on long-term survival. Progressive bronchiolitis obliterans has been reported to occur in 10% of all patients with chronic GVHD  from 3 months to 2 years after HCT. Clinical and pathological findings are similar to those seen after lung or heart-lung transplants  . Histological changes are thought to be due to a graft-versushost reaction, possibly aggravated by infections. Pulmonary infections develop in more than 60% of allogeneic HCT recipients with GVHD compared to about 20% of patients without chronic GVHD. A recent analysis of results in 6523 patients transplanted at FHCRC revealed 51 cases of bronchiolitis obliterans organizing pneumonia (BOOP), all but two after allogeneic transplants. BOOP was diagnosed at 5 Á/2,819 (median 108) days after HCT. The disease was significantly associated with acute and chronic GVHD. The disease progressed in 22% of patients and resolved or was stable in the remaining patients  .