Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used to treat hematologic malignancies. Pulmonary insults in various forms occur in 40%～60% of allo-HSCT recipients and account for approximately 10%～40% of transplant related mortality. Idopathic pneumonia syndrome (IPS) and invasive mold infection (IMI) are commonly pulmonary complications after allo-HSCT, both of which related mortality are as higy as more than 60%. Additonally, the incidence of invasive mold infection, specially of invasive aspergillosis (IA), has increased significantly over the past decades in allo-HSCT recipients as well as in hematological patients receiving chemotherapy,the high mortality of which are partly connectd with the trouble in early diagnosis. As a result, we retrospectively analyzed allo-HSCT recipients during the past 8 years in our center in order to know the incidences and risk factors of IPS and IMI. We expect that this will help the treatment of these two pulmonary complications. Furthoremore, We prospectively discuss the value of circulating galactomannan screening for early diagnosis of invasive aspergillosis in hematological patients.Part one Incidence and risk factors of idiopathic pneumonia syndrome early after allogeneic hematopoietic stem cell transplantationMethods We retrospectively analyzed 190 allo-HSCT recipients at our hospital between the years 2000 and 2007. Survival rate and cumulative incidence rates were evaluated with Kaplan-Meier curves. Logistic regression models was used for univariate analysis and multivariable analyses.Results A total of 15 cases of IPS among 190 allo-HSCT recipients were included in this study. The cumulative incidence rates for IPS at 120 days post-HSCT was 8.6%. Median onset of IPS was 100 (30～119) days post-HSCT. Both univariate analysis and multivariate analyses showed that the significant predictors for IPS were CML as the underlying diease (P=0.007; OR 6.807; 95%CI 1.705～27.176) and aGVHD (P=0.000; OR 1.977; 95%CI 1.356～2.883). The IPS-related motality was as high as 73.5%. The 6-month post-HSCT overall survival of patients with IPS and without IPS was 20.0% and 83.7%, The 1-year post-HSCT overall survival was 20.0% and 71.5%, respectively. Conclusion Compared with the reports abroard, the median onset of IPS in this cohort of patients was later, but the incidence and related mortality was alike. These data confirmed previous findings that incidence of IPS are mostly associated with immune-mediated lung injury, indicating that effectively preventing and timely controling aGVHD may reduce the incidence of IPS.Part two Incidence and risk factors of invasive mold infection following allogeneic hematopoietic stem cell transplantationMethods We retrospectively analyzed 190 allo-HSCT recipients at our hospital between the years 2000 and 2007. Survival rate and cumulative incidence rates were evaluated with Kaplan-Meier curves. Logistic regression and Cox regression models were used for multivariable analyses.Results A total of 20 cases of invasive mold infection (IMI) among 190 allo-HSCT recipients were included in this study , Invasive aspergillosis (IA) was the most commonly observed IMI, the median onset of IMI was 124 days (range: 36～1125 days) post-HSCT, the first year cumulative incidence rates after allo-HSCT of IMI was 12.8%. Multivariate analyses showed that significant predictors of IMI were corticosteroid therapy (P = 0.031; RR 1.656; 95%CI 1.047-2.621) and positive cytomegalovirus antigenemia (P = 0.001; RR 5.301; 95% CI 1.902-14.772). The 1-year cumulative incidence rates of IMI after corticosteroid therapy was 17.2%. Mortality rates of IMI at 12 weeks after diagnosis of IMI was 60%. IMI-related mortality was related to the large dose of corticosteroid (2 mg/kg/day or more) (P=0.009; RR: 20.841; 95% CI: 2.151～201.944) administered at the time of IFI diagnosis and neutropenia (P=0.032; RR: 7.043; 95% CI: 1.186～41.827).Conclusion Our single-center data analysis demonstrated a high incidence of IA, furthermore, incidence and mortality of invasive mold infection are mostly associated with immunodeficiency caused by immunosuppressive therapy and virus infection.Part three Value of circulating galactomannan screening for early diagnosis of invasive aspergillosis in hematological patientsMethods We prospectively evaluated the diagnostic value of twice-weekly screening for circulating Aspergillus fumigatus with sanditch enzyme linked immunosorbent assay. Results On the basis of the analysis of 472 serum samples from 113 episodes of 92 patients, the sensitivity, specificity, positive and negative predictive values of the sanditch ELISA for proven and probable IA cases were 83.3%, 91.1%, 78.9%, and 93.1%, respectively, when samples with 2 consecutive positive results≥0.7 were used. Furthormore, GM antigenemia was detected before the onset of radiologic signs with a median of 7 days (range, 1～14 days), before isolation of Aspergillus with a median of 4 days (range, 1～7 days), and before anti-fungal therapy with a median of 6 days (range, 1～15 days).Conclusions The sanditch ELISA for GM detection is a reliable method for early diagnosis of IA in patients with haematological diseases.