Association between acute graft versus host disease and lung injury after allogeneic haematopoietic stem cell transplantation.
OBJECTIVE
To investigate the characteristics of chest high-resolution computed tomography (HRCT) and pathogenesis of acute graft versus host disease (acute GVHD)-induced lung injury after allogeneic haematopoietic stem cell transplantation (allo-HSCT).


METHODS
A study of 47 patients with acute GVHD of grades II-IV describes the clinical manifestations and characteristics of chest HRCT of acute GVHD-induced lung injury. Detection of serum interferon gamma (IFNgamma) and tumour necrosis factor alpha (TNFalpha) were performed before the treatment for acute GVHD. Transbronchial biopsy was performed in four patients whose chest HRCT did not recover completely after treatment for acute GVHD. Pulmonary function was measured in patients who survived more than 6 months in every 3 months.


RESULTS
Chest HRCT scans were performed in 47 cases and 20 cases showed abnormal in which 17 cases were suspected of acute GVHD-induced lung injury. In 17 patients with acute GVHD-induced lung injury, HRCT revealed diffused interstitial infiltrate in five cases, diffused interstitial and alveolar infiltrate in seven cases, diffused interstitial and segmental lobar alveolar infiltrate in five cases accompanied by bilateral pleural effusion and hydropericardium in nine patients. There was no statistical significance between the levels of serum IFNgamma and TNFalpha in cases with and without lung injury, but the levels of serum IFNgamma and TNFalpha in patients were significantly higher than the healthy group (IFNgamma: p=0.000, TNFalpha: p=0.000). The histopathology of the lung tissue was characterized by disorganization, epithelial cell damage, interstitial fibroplasias and interstitial T lymphocyte or macrophage infiltrate. Forty-seven cases all attained the treatment for acute GVHD, and the total effective rate and the rate of completely remission (CR) were 74.47 and 55.32%, respectively. The total effective rate and the rate of CR in the treatment for acute GVHD-induced lung injury were 94.12 and 58.82%, respectively. The effective rate of treatment for acute GVHD-induced lung injury positively correlated with that for acute GVHD (r=0.771, p=0.001). Three cases in nine cases with lung injury and three cases in 15 cases without lung injury who survived more than 6 months developed late-onset non-infectious lung injury. Eleven patients of 24 patients who survived more than 6 months had abnormal pulmonary function, including seven patients in nine patients with acute GVHD-induced lung injury and four patients in 15 patients without acute GVHD-induced lung injury. There was no difference in the incidence of late-onset non-infectious lung injury, but significance in the incidence of abnormal pulmonary function between cases with and without lung injury (p=0.033, cross-tabs).


CONCLUSIONS
These results suggested that the lung might be one of the target organs of acute GVHD and participation of T lymphocyte, macrophage and cytokines such as IFNgamma and TNFalpha might play a role in the pathogenesis of acute GVHD-induced lung injury. Acute GVHD-induced lung injury may progress to late-onset non-infectious lung injury.
Liu
Qi-Fa
QF
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China. liuqifa@fimmu.com
Luo
Xiao-Dan
XD
Ning
Juan
J
Xu
Dan
D
Fan
Zhi-Ping
ZP
Sun
Jing
J
Zhang
Yu
Y
Xu
Bing
B
Wei
Yong-Qiang
YQ
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000150:complications / Q000209:etiology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood; D055370:Lung Injury / Q000097:blood / Q000150:complications* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D014057:Tomography, X-Ray Computed / Q000379:methods; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014916:Whole-Body Irradiation; D055815:Young Adult
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma