One of the most severe manifestations of cGVHD is bronchiolitis obliterans syndrome (BOS), an insidious lung disease occurring in a subset of patients after allogeneic HSCT, characterized by progressive circumferential fibrosis and cicatrization of the small terminal airways. Since BOS is morbid and frequently fatal complication, insight into the features that distinguish those patients with cGVHD who develop BOS from those who do not could be important in better understanding of the disease and its clinical implications, and may lead to developing of new treatment modalities and strategies. The aim of this study was to compare demographic characteristics, clinical manifestations, laboratory parameters, functional and psychological status, activity and severity of cGVHD, and overall survival (OS) between cGVHD patients with and without BOS.
46 adult cGVHD patients with BOS (diagnosed using modified NIH criteria as: FEV1<75% and a) FEV1/FVC ratio <0.7 or b) air trapping defined by both RV or RV/TLC and CT criteria) and 165 adult cGVHD patients without BOS were enrolled from 2004–2011 into the cross sectional NCI cGVHD natural history study. A detailed clinical, laboratory, and functional evaluation was performed, specifically obtaining: NIH organ system severity scoring, PFTs, chest CT, cGVHD activity, intensity of immunosuppression, number of prior systemic therapies (PST), cGVHD global rating score reported by clinician and patient (form A and B), SF36 (PCS, MCS), Lee symptom scale (total and breathing subscale), HAP (MAS, AAS), 2-minute walk velocity, and grip strength. The association between these factors and BOS was initially evaluated using univariate methods to test for a difference, and then multivariable logistic regression for prediction. Median follow-up of survivors was 47 months (range 10–90).
cGVHD patients with and without BOS were not different regarding age, gender, primary diagnosis, conditioning intensity, donor gender and cell source, time from transplant to enrollment or to cGVHD diagnosis, median number of PST for cGVHD, history of aGVHD, cGVHD onset and classification, intensity of immunosuppression, and cGVHD activity. cGVHD patients with BOS had fewer HLA matched donors (p=0.0044), worse cGVHD NIH global severity (p<0.0001), worse NIH lung (p<0.0001) and eye (p=0.011) scores, worse respiratory symptoms (p<0.0001), worse cGVHD global rating score by clinician (p=0.0038) and patient (p=0.0089), lower Karnofsky (p=0.0001), longer time from cGVHD diagnosis to enrollment (0.032), lower Schirmer's test (p=0.029), lower walk velocity (p=0.0084), lower HAP MAS and AAS (p<0.0001) scores, more breathing symptoms (p<0.0001) and greater fatigue (p=0.04). Those with BOS also reported inferior physical (p=0.008) and mental (p=0.006) health. Having BOS was also associated with higher platelet count (p=0.0089), WBC (p=0.028), ANC (p=0.046), LDL (p=0.0029), and IgA (p=0.032) comparing to cGVHD patients without BOS. In a predictive statistical model higher platelet count, higher RV and higher lung function score (LFS) can correctly predict 84.8% cGVHD patients with BOS and 80.4% without BOS. BOS did not significantly affect OS; however, in univariate analyses, BOS patients with FEV1<50% had significantly shorter OS compared to patients without BOS (p<0.0001) and compared to those who had BOS with FEV1≥50% (p=0.0006). A 4 year survival was 95% for patients with BOS and FEV1>=50, 78% for patients without BOS, and 37% for patients with BOS and FEV1< 50%, respectively.
cGVHD patients with BOS had worse clinical manifestations and cGVHD severity as well as inferiorities in functioning and self-assessed physical and mental health. The impact of BOS on survival was restricted to an effect of FEV1<50% among those with BOS.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.