Late Noninfectious Pulmonary Complications in Hematopoietic Stem Cell Transplantation
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ABSTRACT:
SUBMITTER: Nates J
PROVIDER: S-EPMC7123191 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Project description:Haematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant and nonmalignant conditions. Pulmonary complications, both infectious and noninfectious, are a major cause of morbidity and mortality in patients who undergo HSCT. Recent advances in prophylaxis and treatment of infectious complications has increased the significance of noninfectious pulmonary conditions. Acute lung injury associated with idiopathic pneumonia syndrome remains a major acute complication with high morbidity and mortality. On the other hand, bronchiolitis obliterans syndrome is the most challenging chronic pulmonary complication facing clinicians who are taking care of allogeneic HSCT recipients. Other noninfectious pulmonary complications following HSCT are less frequent. This review provides a clinical update of the incidence, risk factors, pathogenesis, clinical characteristics and management of the main noninfectious pulmonary complications following HSCT.
| S-EPMC9488720 | biostudies-literature
Project description:Noninfectious pulmonary toxicity (NPT), a significant complication of allogeneic hematopoietic cell transplantation (alloHCT), includes idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), and cryptogenic organizing pneumonia (COP), with an overall incidence ranging from 1% to 15% in different case series and a variable mortality rate. A registry study of the epidemiology and outcomes of NPT after alloHCT has not been conducted to date. The primary objective of the present study was to assess the incidence of and risk factors for IPS, DAH, and COP; the secondary objective was to assess overall survival (OS) in patients developing NPT. This retrospective study included adult patients who underwent alloHCT between 2008 and 2017 and reported to the Center for International Blood and Marrow Transplant Research. Multivariable Cox proportional hazards regression models were developed to identify the risk factors for development of NPT and for OS, by including pretransplantation clinical variables and time-dependent variables of neutrophil and platelet recovery, and acute graft-versus-host disease (GVHD) post-transplantation. This study included 21,574 adult patients, with a median age of 55 years. According to the HCT Comorbidity Index (HCT-CI), 24% of the patients had moderate pulmonary comorbidity and 15% had severe pulmonary comorbidity. The cumulative incidence of NPT at 1 year was 8.1% (95% confidence interval [CI], 7.7% to 8.5%). Individually, the 1-year cumulative incidences of IPS, DAH, and COP were 4.9% (95% CI, 4.7% to 5.2%), 2.1% (95% CI, 1.9% to 2.3%), and .7% (95% CI, .6% to .8%), respectively. Multivariable analysis showed that severe pulmonary comorbidity, grade II-IV acute GVHD, mismatched unrelated donor and cord blood transplantation, and HCT-CI score ≥1 significantly increased the risk of NPT. In contrast, alloHCT performed in 2014 or later, non-total body irradiation (TBI)- and TBI-based nonmyeloablative conditioning and platelet recovery were associated with a decreased risk. In a landmark analysis at day+100 post-transplantation, the risk of DAH was significantly lower in patients who had platelet recovery by day +100. Multivariable analysis for OS demonstrated that NPT significantly increased the mortality risk (hazard ratio, 4.2; P < .0001).
| S-EPMC9197865 | biostudies-literature
Project description:BackgroundLate onset non-infectious pulmonary complications (LONIPCs) following allogenic hematopoietic stem cell transplantation (allo-HSCT) confer a significant mortality risk. Lung transplantation (LTx) has the potential to provide survival benefit but the impact of prior allo-HSCT on post-LTx outcomes is not well studied.MethodsThis retrospective, single-centre cohort study assessed the post-LTx outcomes of adults with LONIPCs of allo-HSCT. Outcomes of LTx for LONIPCs were compared to propensity-score matched LTx controls (n = 38, non-HSCT) and recipients of re-LTx (n = 70) for chronic lung allograft dysfunction (CLAD).ResultsNineteen patients underwent DLTx for LONIPCs of allo-HSCT between 2003 and 2019. Post-LTx survival was 50% at 5-years. Survival to 1-year post-LTx was similar to matched controls (p = 0.473). Survival, conditional on 1-year survival, was lower in the allo-HSCT cohort (p = 0.034). An increased risk of death due to infection was identified in the allo-HSCT cohort compared to matched controls (p = 0.003). Compared to re-LTx recipients, the allo-HSCT cohort had superior survival to 1-year post-LTx (p = 0.034) but conditional 1-year survival was similar (p = 0.145).ConclusionThis study identifies an increased risk of post-LTx mortality in recipients with previous allo-HSCT, associated with infection. It supports the hypothesis that allo-HSCT LTx recipients are relatively more immunosuppressed than patients undergoing LTx for other indications. Optimisation of post-LTx immunosuppressive and antimicrobial strategies to account for this finding should be considered.
| S-EPMC8025894 | biostudies-literature
Project description:The authors sought to better understand the combined effects of pretransplant, transplant, and post-transplant factors in determining risks of serious cardiovascular disease after hematopoietic cell transplantation (HCT). Hospitalizations and deaths associated with serious cardiovascular outcomes were identified among 1379 Washington State residents who received HCT (57% allogeneic and 43% autologous) at a single center from 1985 to 2005, survived ≥ 2 years, and followed through 2008. Using a nested case-cohort design, relationships (hazard ratios [HRs]) between potential risk factors and outcomes were examined among affected survivors and a randomly selected subcohort (N = 509). After 7.0 years of median follow-up (range, 2.0 to 23.7), the 10-year cumulative incidence of ischemic heart disease, cardiomyopathy, stroke, and all-cause cardiovascular death was 3.8%, 6.0%, 3.5%, and 3.7%, respectively. In multivariable analysis, increased pretransplant anthracycline was associated with cardiomyopathy. Active chronic graft-versus-host disease was associated with cardiovascular death (HR, 4.0; 95% confidence interval, 1.1 to 14.7); risk was otherwise similar between autologous versus allogeneic HCT recipients. Independent of therapeutic exposures, pretransplant smoking, hypertension, dyslipidemia, diabetes, and obesity conferred additional risk of all outcomes except stroke (HR ≥ 1.5 for each additional risk factor, P < .03). Hypertension and dyslipidemia at 1 year with persistence of these conditions 2 or more years after HCT also were associated with independent risks of multiple outcomes. HCT survivors with preexisting or newly developed and persistent cardiovascular risk factors remain at greater risk of subsequent serious cardiovascular disease compared with other survivors, independent of chemo- and radiotherapy exposures. These survivors should receive appropriate follow-up and be considered for primary intervention.
| S-EPMC4019708 | biostudies-literature
Project description:The utility of transbronchial biopsy in the management of pulmonary complications following hematopoietic stem cell transplantation (HSCT) has shown variable results. Herein, we examine the largest case series of patients undergoing transbronchial biopsy following HSCT. We performed a retrospective analysis of 130 transbronchial biopsy cases performed in patients with pulmonary complications post HSCT. Logistic regression models were applied to examine diagnostic yield, odds of therapy change and complications. The most common histologic finding on transbronchial biopsy was a nonspecific interstitial pneumonitis (n=24 cases, 18%). Pathogens identified by transbronchial biopsy were rare, occurring in <5% of cases. A positive transbronchial biopsy significantly increased the odds of a subsequent change in corticosteroid therapy (odds ratio (OR)=3.12; 95% confidence interval (CI) 1.18-8.23; P=0.02) but was not associated with a change in antibiotic therapy (OR=1.01; 95% CI 0.40-2.54; P=0.98) or changes in overall therapy (OR=1.92; 95% CI 0.79-4.70; P=0.15). Patients who underwent a transbronchial biopsy had increased odds of complications related to the bronchoscopy (OR=3.33, 95% CI 1.63-6.79; P=0.001). In conclusion, transbronchial biopsy may contribute to the diagnostic management of noninfectious lung injury post HSCT, whereas its utility in the management of infectious pulmonary complications of HSCT remains low.
| S-EPMC5803310 | biostudies-literature
Project description:Significant advances have been made in allogeneic transplantation for both adults and pediatric transplant recipients over the past 20 years, corresponding with dramatic declines in treatment-related mortality (TRM). The cumulative incidence of TRM at 1 year following unrelated donor transplants has decreased from 40 to 15 % between 1987 and 2006 for children with acute leukemia, the primary indication for transplant in the pediatric population (MacMillan et al., Biol Blood Marrow Transpl 14(9 Suppl):16–22, 2008). Improvements in conditioning regimen, supportive care, and human leukocyte antigen (HLA) testing have all been associated with incremental improvements in survival during this period. In particular, the management of both infectious and noninfectious organ complications has changed dramatically, with improved sensitivity for diagnostic testing for pathogens and tremendous improvements in our understanding of organ complications. Two organ complications in particular, pulmonary and hepatic, have been a major focus of investigation over the past several decades. The introduction of tumor necrosis factor (TNF) inhibitors for the management of acute, noninfectious lung injury and the introduction of an endothelial stabilizing agent (defibrotide) for the management of hepatic veno-occlusive disease have been major advances in the past decade.
| S-EPMC7123560 | biostudies-literature
Project description:BACKGROUND:Transfusion of blood products is an essential component of the hematopoietic cell transplantation (HCT) process. Blood transfusion carries several risks including, but not limited to, lung injury. The effect of transfusions on lung complications after HCT has not been previously investigated. STUDY DESIGN AND METHODS:We retrospectively studied 215 adult allogeneic HCT recipients at the University of Minnesota and examined the association between transfusion of blood components and development of lung complications after HCT. Patients without lung complications were used as the control group. RESULTS:A total of 113 (58%) of the patients developed lung injury events before Day 180 after HCT. Six-month survival was significantly lower in the lung event group (52%) versus the controls (78%; p = 0.01). Patients who eventually developed lung events received more transfusion episodes per week in the first month after HCT (median, 4.3 vs. 2.7 for controls), platelet units per week (3.5 vs. 2.0), and RBC units per week (1.8 vs. 1.4; p < 0.01) for all. In a multivariable analysis, each additional transfusion before Day +30 was associated with a 2.7% higher risk of lung complication (95% confidence interval, 0.8-4.8; p = 0.01), adjusting for time to engraftment, conditioning intensity, and donor type. Blood utilization increased after the lung event and remained high for several months relative to controls. CONCLUSION:Our data suggest that transfusion of blood products is associated with and may further complicate lung complications after HCT. Cautious use of blood components in the post HCT period is recommended.
| S-EPMC5577937 | biostudies-literature
Project description:Long-term survival after hematopoietic cell transplantation (HCT) is now an expected outcome. The growing population of survivors is at risk of developing treatment-related complications, including cardiovascular disease (CVD). A nested case-controlled design was used to identify clinical and treatment-related risk factors for development of late (1+ years after HCT) CVD. Cases were identified from a cohort of 1+-year survivors who underwent transplantation at City of Hope between 1977 and 2006. Controls (HCT survivors without CVD) were matched on age, year of HCT, type of HCT, and duration of follow-up. Sixty-three patients with late CVD were identified, 44 (69.8%) with a coronary artery event and 19 (30.2%) with a cerebrovascular event. Median age at HCT was 49.0 years. Median age at onset of late CVD was 54.0 years; 66.7% of the affected patients had undergone autologous HCT. Multivariate logistic regression analysis showed that the presence of multiple cardiovascular risk factors (2 or more of the following: obesity, dyslipidemia, hypertension, and diabetes) after HCT was associated with a 5.2-fold increased risk of late CVD (P < .01), and that pre-HCT chest radiation exposure was associated with a 9.5-fold greater risk of coronary artery disease (P = .03). Pre-HCT exposure to chest radiation and the presence of comorbidities were primarily responsible for the risk associated with late CVD after HCT. These data form the basis for developing predictive models for identifying high-risk individuals for targeted surveillance and aggressive management of comorbidities.
| S-EPMC2888883 | biostudies-literature
Project description:Hematopoietic stem cell transplantation (HSCT) has been an effective method for treating a wide range of malignant or non-malignant disorders. In case of an autologous HSCT, patients receive their own stem cells after myeloablation before extraction. Allogeneic HSCT uses stem cells derived from a donor. Despite being associated with a high risk of early and long-term complications, it is often the last curative option. 229 pediatric patients, who between 1 January 2005 and 31 December 2015 received an HSCT at the University Children's Hospital Wuerzburg, were studied. Correlations between two groups were calculated with the Chi square test or with a 2x2-contingency table. To calculate metric variables, the Mann-Whitney-U-test was used. Survival curves were calculated according to Kaplan and Meier. Significance was assumed for results with a p-value <0.05 (CI (Confident Interval) 95%). We retrospectively analyzed 229 pediatric patients (105 females, 124 males) for early and late complications of allogeneic and autologous hematopoietic stem cell transplantation. Median age at HSCT was seven years. Underlying diseases were leukemia (n = 73), lymphoma (n = 22), solid tumor (n = 65), CNS (central nervous system)- tumor (n = 41), and "other diseases" (n = 28). Survival times, overall survival, and event-free survival were calculated. Of all patients, 80.8% experienced complications of some degree, including mild and transient complications. Allo-HSCT (allogeneic HSCT) carried a significantly higher risk of complications than auto-HSCT (autologous HSCT) (n = 118 vs. n = 67; p = < .001) and the remission rate after allo-HSCT was also higher (58.7% vs. 44,7%; p = .032). Especially infection rates and pulmonary complications are different between auto- and allo-HSCT. Leukemia patients had the highest risk of early and late complications (95,0%; p < .001). Complications within HSCT are major risk factors following morbidity and mortality. In order to detect complications and risk factors early, strict recordings are needed to reduce the rate of complication by recognition and prevention of triggering factors. In the future, these factors should receive greater attention in the planning of HSCT post-transplantation care in order to improve the results of the transplantation and establish protocols to prevent their occurrence.
| S-EPMC6191171 | biostudies-literature
Project description:BACKGROUND: Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for many nonmalignant disorders, such as autoimmune disorders, inborn metabolic disorders, hemoglobinopathies, and immunodeficiency disorders. Autoimmune complications (AICs) after HSCT, such as autoimmune cytopenias, autoimmune hepatitis, primary biliary cirrhosis, and autoimmune cutaneous manifestations, are still neither well defined nor characterized. PATIENTS: Between 2000 and 2012, 92 patients (47 males, 45 females) were treated with HSCT in our hospital, 51 with congenital hemoglobinopathies, 19 with primary immunodeficiency disease, 10 with metabolic disorders, five with Fanconi anemia, three with aplastic anemia, and four with familial hemophagocytic lymphohistiocytosis. RESULTS: Mean age at HSCT was 6.4 years (range, 0.2-32 years) and mean duration of followup after HSCT was 6.81 years (range, 1-11 years). Sixteen (17.4%) patients developed chronic GVHD and five (5.4%) showed sclerodermatous features. Five (5.4%) patients were diagnosed with scleroderma manifestations, six (6.5%) with vitiligo, six (6.5%) with autoimmune hemolytic anemia (AIHA), six (6.5%) with idiopathic thrombocytopenia, three (3.3%) with mild leucopenia, two (2.2%) with aplastic anemia, two (2.2%) (one boy, one girl) with autoimmune thyroid disease, and one (1.1%) with autoimmune hepatitis. CONCLUSIONS: It was concluded that AICs are clinically significant complications after HSCT that contribute to morbidity but not to mortality. AICs are more frequent after HSCT for metabolic disorders, and sclerodermatous GVHD is more significant in children who underwent allogeneic HSCT for hemoglobinopathies. The potential to identify risk factors for AICs could lead to less morbidity and mortality and to maintain the patient's quality of life.
| S-EPMC3916029 | biostudies-other