Association between Acute Graft Versus Host Disease and Early Lung Injury after Allogenic Hematopoietic Stem Cell Transplantation.

Objective: To investigate the clinical characteristics and pathogenesis of acute graft versus host disease (aGVHD) inducing lung injury after allogenic hematopoietic stem cell transplantation (allo-HSCT).

Methods: aGVHD inducing lung injury was investigated in 47 patients who had aGVHD of grade II–IV. High-resolution computed tomography (HRCT) of the chest and detections of serum interferon γ (IFNγ) and tumor necrosis factor (TNFα) were performed before the treatment for aGVHD. Transbronchial biopsies under the bronchofibroscope were performed in 4 patients whose HRCT scans did not show completely remission after treatment for aGVHD. Examination of hydrothorax was taken in 4 patients who had medium quantity of pleural effussion. Statistical analysis was performed using SPSS/PC version 13.0.

Results: In 47 cases, HRCT scans of the chest were abnormal in 20 cases. 17 cases were diagnosed of aGVHD inducing lung injury by HRCT scans. The characteristics of imageology are diffused interstitia infiltrates in 5 cases, diffused interstitial and alveolar infiltrates in 7 cases, diffused interstitial and segmental lobar infiltrates in 5 cases and bilateral pleural effusion accompanied by hydropericardium in 9 cases including 4 cases with myocardial hypertrophy. Serum levels of IFNγ and TNFα of lung injury cases were 6.901 ± 1.751ng/ml and 399.514 ± 101.598pg/ml and cases without lung injury were 6.280±1.150ng/ml and 427.871 ± 83.287 pg/ml, respectively. No statistical significant was shown between serum levels of IFNγ and TNFα in these two groups. Examination of pleural effusion showed white blood cell count (1200±517.204/μl,800∼2200/μl) and the quantity of proteinum (38.00±13.06g/L, 25.00∼62.00g/L) increased. The histopathology of lung injury in 4 cases was characteristic by disorganization, epithelial cell damage, interstitial fibroplasias and interstitial lymphocytic infiltrates which mainly consisted of T lymphocytes by immunohistochemistry. 47 cases attained treatment for aGVHD. The total effective rate of treatment for aGVHD was 74.47% with the rate of complete response (CR) of 44.67%. The effective rate of treatment for aGVHD inducing lung injury was 94.12% with the rate of CR of 58.82%. Comparison between effective rate of treatment for aGVHD and for aGVHD inducing lung injury showed no statistical significant (P=0.169). 3 cases developed late noninfectious lung injury in 9 cases with lung injury and 3 cases in 15 cases without lung injury who survived more than 6 months. The difference of the morbidity of late noninfectious lung injury was not significant between cases with and without lung injury.

Conclusions: Lung is one of the targets of aGVHD. Early noninfectious lung injury after allo-HSCT is primarily caused by aGVHD. The mechanism of aGVHD inducing lung injury is related to T lymphocyte. Early noninfectious lung injury induced by aGVHD can progress to be late noninfectious lung injury.