Assessment of worsening cGVHD reflective of cGVHD pathophysiology that requires urgent attention. (A) Decrease in FEV1 may reflect pathology of bronchiolitis obliterans found in cGVHD. High lung symptom score carries a high risk of death.102 Pulmonary function test abnormalities, specifically evidence of obstruction (FEV1/FVC <0.7) and decreases in FEV1, should raise strong suspicion for development of lung cGVHD, because FEV1 decrease without evidence of restrictive disease may reflect underlying small airway occlusion related to extracellular matrix deposited within or around the airways in cGVHD. Because a drop of FEV1 alone is an indicator of impaired lung function and could be also due to restrictive lung disease, FEV1 is a useful indicator of obstruction only when FEV1/FVC is <0.7 (consistent with obstructive lung disease). (B) Abnormal liver tests may reflect liver pathology in cGVHD that is associated with increased mortality.103 cGVHD of the liver can be diagnosed and tracked in patients using total bilirubin and alkaline phosphatase per NIH consensus criteria.25 An increase in total bilirubin occurs when conjugated bilirubin is not excreted, either because of inflammation or loss of the ducts. When the ducts are not functioning properly, alkaline phosphatase rises. Dysfunctional bile ducts can be due to bile duct dropout, presumably a result of cellular damage and preceding inflammation or (more rarely) fibrosis. Infectious or drug-induced causes, in some cases, should be ruled out via biopsy. (C) Significant weight loss with or without diarrhea warrants further investigation because of its association with increased mortality.94,104 The etiology of weight loss may be multifactorial and, importantly, may be reversible (eg, decreased calorie intake related to oral cGVHD, esophageal stricture, or intestinal malabsorption). (D) Abnormalities found on the complete blood count are known prognostic factors,9,79,101,105 including in newly diagnosed cGVHD.81,105 CMV, cytomegalovirus; EBV, Epstein-Barr virus; HSV, herpes simplex virus; PCR, polymerase chain reaction.