Pulmonary Complications in Hematopoietic Stem Cell Transplant Recipients-A Clinician Primer.
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ABSTRACT:
SUBMITTER: Astashchanka A
PROVIDER: S-EPMC8348211 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hematopoietic stem cell transplantation (HSCT) is a highly advanced technique that offers a potential cure for an increasing number of life-threatening diseases. Enormous progress achieved in the last decade, including the refinement of donor selection and advancements in patient supportive care, had significantly improved transplant outcomes; however, invasive infections, graft-vs.-host disease (GVHD) and other serious complications still represent a major source of morbidity and mortality in HSCT recipients. The damage of anatomical barriers due to pre-transplant conditioning, a severely damaged immune function and a profound disruption in the composition of gut microbial commensals (gut microbiota) are alterations inherent to the transplant procedure that are directly implicated in the development of invasive infections and other HSCT complications. Although HLA-matching represents the most important genetic predictor of transplant outcomes, genetic variants in non-HLA genes, especially single nucleotide polymorphisms (SNPs) of genes encoding proteins associated with the immune response to tissue injury and pathogen infection have also been proposed as additional risk factors implicated in the occurrence of HSCT complications. Furthermore, although the microbiota composition is affected by several factors, recent evidence suggests that certain host genetic variants are associated with an altered composition of the gut microbiome and may, therefore, predispose some individuals to invasive infectious complications. This article summarizes the current understanding of the influence that genetic variants in non-HLA genes have on the development of infectious complications in HSCT recipients.
| S-EPMC6190889 | biostudies-literature
Project description:Bacterial infections are major complications after Hematopoietic Stem Cell Transplant (HSCT). They consist mainly of bloodstream infections (BSI), followed by pneumonia and gastrointestinal infections, including typhlitis and Clostridium difficile infection. Microbiological data come mostly from BSI. Coagulase negative staphylococci and Enterobacteriaceae are the most frequent pathogens causing approximately 25% of BSI each, followed by enterococci, P. aeruginosa and viridans streptococci. Bacterial pneumonia is frequent after HSCT, and Gram-negatives are predominant. Clostridium difficile infection affects approximately 15% of HSCT recipients, being more frequent in case of allogeneic than autologous HSCT. The epidemiology and the prevalence of resistant strains vary significantly between transplant centres. In some regions, multi-drug resistant (MDR) Gram-negative rods are increasingly frequent. In others, vancomycin-resistant enterococci are predominant. In the era of increasing resistance to antibiotics, the efficacy of fluoroquinolone prophylaxis and standard treatment of febrile neutropenia have been questioned. Therefore, a thorough evaluation of local epidemiology is mandatory to decide the need for prophylaxis and the choice of the best regimen for empirical treatment of febrile neutropenia. For the latter, individualised approach has been proposed, consisting of either escalation or de-escalation strategy. De-escalation strategy is recommended since resistant bacteria should be covered upfront, mainly in patients with severe clinical presentation and previous infection or colonisation with a resistant pathogen. Non-pharmacological interventions, such as screening for resistant bacteria, applying isolation and contact precautions should be put in place to limit the spread of MDR bacteria. Antimicrobial stewardship program should be implemented in transplant centres.
| S-EPMC4500472 | biostudies-literature
Project description:To review the most recent data regarding the epidemiology, risks factors, and outcomes among hematopoietic stem cell transplant recipients with Clostridium difficile infection (CDI).With the emergence of an epidemic strain of C. difficile known as NAP1 in the early 2000s, rates of this infection have escalated globally. Hematopoietic stem cell transplant recipients appear to be one of the most vulnerable populations for the development of CDI. Traditional risk factors for CDI including antimicrobial exposure and older age are likely only a piece of the overall risk profile, with recent study results also emphasizing other factors such as transplant type, conditioning regimen, and graft-versus-host disease (GVHD). The relationship between CDI and subsequent development of GVHD, particularly of the gastrointestinal tract, is of specific interest. A bidirectional relationship of association has been highlighted in a number of recent studies and underscores the need for further prospective studies to address the potential indirect effects of alloreactivity induced by CDI.CDI has emerged as one of the most common infections in the early transplant period. Recent studies have begun to address the epidemiology of disease, risk factors for, and outcomes after infection in the stem cell transplant. However, more research is needed to unravel the observed relationship between CDI and GVHD.
| S-EPMC4222064 | biostudies-other
Project description:Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients' depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed a cohort of patients that were transplanted between 1 January 2010 and 31 October 2019 in the Geneva University Hospitals with at least one RVI before or after transplantation. At least one RVI was detected in 319/533 (63.5%) transplanted patients. Rhinoviruses were most frequently identified (37%), followed by human coronaviruses (17.1%), parainfluenza viruses (13.9%), and influenza viruses (9.9%). First infection in the post-transplant period occurred at a mean time of 334 days (SD 338). Specific analysis of a subgroup of 65 patients with pre-transplant RVIs was performed. Among them, 39 (59%) patients had symptoms and 14 (21.2%) had a lower respiratory tract infection. Four patients (6.1%) (three rhinovirus and one influenza) needed an intensive care unit admission, of which, three (4.5%) (two rhinovirus and one influenza) were intubated. The patient with influenza infection diagnosed the day of the transplantation died within the first 30 days of the infection. Two patients with rhinovirus infection died within 3 months of unrelated causes. Our data show that rhinovirus infections are predominant in allo-HSCT patients, including among pre-transplant infections; however, mortality due to pre-transplant RVI is low and was only clearly identified in one patient with influenza infection. RVI within the month preceding allo-HSCT is not associated with direct morbidity or mortality in this cohort.
| S-EPMC8879386 | 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:Hematopoietic stem cell transplantation (HSCT) is an established therapeutic modality for a number of malignant and nonmalignant conditions. Pulmonary complications following HSCT are associated with increased mortality and morbidity. These complications may be classified into infectious versus noninfectious, and early versus late based on the time of occurrence post-transplant. Thus, exclusion of infectious etiologies is the first step in the diagnoses of pulmonary complications. Late onset noninfectious pulmonary complications typically occur 3 months post-transplant. Bronchiolitis obliterans is the major contributor to late-onset pulmonary complications, and its clinical presentation, pathogenesis, and current therapeutic approaches are discussed. Idiopathic pneumonia syndrome is another important complication which usually occurs early, although its onset may be delayed. Organizing pneumonia is important to recognize due to its responsiveness to corticosteroids. Other late onset noninfectious pulmonary complications discussed here include pulmonary venoocclusive disease, pulmonary cytolytic thrombi, pleuroparenchymal fibroelastosis, thoracic air leak syndrome, and posttransplant lymphoproliferative disorders.
| S-EPMC7123191 | biostudies-literature
Project description:Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in promising strategies to enhance or restore critical immune functions in allogeneic HSCT recipients. Potential approaches include the administration of granulocytes, since neutropenia is the single most important risk factor for invasive fungal infection, and preliminary clinical results suggest a benefit of adoptively transferred donor-derived antifungal T cells. In vitro data and animal studies demonstrate an antifungal effect of natural killer cells, but clinical data are lacking to date. This review summarizes and critically discusses the available data of immunotherapeutic strategies in allogeneic HSCT recipients suffering from invasive fungal infection.
| S-EPMC3566394 | biostudies-literature
Project description:BackgroundPulmonary complications, including infections, are highly prevalent in patients after hematopoietic cell transplantation with chronic graft-vs-host disease. These comorbid diseases can make the diagnosis of early lung graft-vs-host disease (bronchiolitis obliterans syndrome) challenging. A quantitative method to differentiate among these pulmonary diseases can address diagnostic challenges and facilitate earlier and more targeted therapy.Study design and methodsWe conducted a single-center study of 66 patients with CT chest scans analyzed with a quantitative imaging tool known as parametric response mapping. Parametric response mapping results were correlated with pulmonary function tests and clinical characteristics. Five parametric response mapping metrics were applied to K-means clustering and support vector machine models to distinguish among posttransplantation lung complications solely from quantitative output.ResultsCompared with parametric response mapping, spirometry showed a moderate correlation with radiographic air trapping, and total lung capacity and residual volume showed a strong correlation with radiographic lung volumes. K-means clustering analysis distinguished four unique clusters. Clusters 2 and 3 represented obstructive physiology (encompassing 81% of patients with bronchiolitis obliterans syndrome) in increasing severity (percentage air trapping 15.6% and 43.0%, respectively). Cluster 1 was dominated by normal lung, and cluster 4 was characterized by patients with parenchymal opacities. A support vector machine algorithm differentiated bronchiolitis obliterans syndrome with a specificity of 88%, sensitivity of 83%, accuracy of 86%, and an area under the receiver operating characteristic curve of 0.85.InterpretationOur machine learning models offer a quantitative approach for the identification of bronchiolitis obliterans syndrome vs other lung diseases, including late pulmonary complications after hematopoietic cell transplantation.
| S-EPMC8097633 | biostudies-literature
Project description:Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach. Our study defines the functional kinetics of each TCRA and TCRB clone, and changes in T-cell diversity (with identification of CDR3 sequences) and the extent of clonal expansion of certain T-cells. Using this approach, our study demonstrates that higher percentage of cord-blood cells at 30 days after transplant was correlated with higher diversity of TCR repertoire, implicating the role of cord-chimerism in enhancing immune recovery. Importantly, we found that GVHD and relapse, exclusive of each other, were correlated with lower TCR repertoire diversity and expansion of certain T-cell clones. Our results highlight novel insights into the balance between GVHD and GVL effect, suggesting that higher diversity early after transplant possibly implies lower risks of both GVHD and relapse following the HSCT transplantation.
| S-EPMC4559843 | biostudies-literature
Project description:Human cytomegalovirus (HCMV) reactivation is a major infectious cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). HCMV is a ubiquitous beta-herpesvirus which asymptomatically infects immunocompetent individuals but establishes lifelong latency, with the potential to reactivate to a life-threatening productive infection when the host immune system is suppressed or compromised. Opportunistic HCMV reactivation is the most common viral complication following engraftment after HSCT and is associated with a marked increase in non-relapse mortality, which appears to be linked to complex effects on post-transplant immune recovery. This minireview explores the cellular sites of HCMV latency and reactivation in HSCT recipients and provides an overview of the risk factors for HCMV reactivation post-HSCT. The impact of HCMV in shaping post-transplant immune reconstitution and its relationship with patient outcomes such as relapse and graft-versus-host disease will be discussed. Finally, we survey current and emerging strategies to prevent and control HCMV reactivation in HSCT recipients, with recent developments including adoptive T cell therapies to accelerate HCMV-specific T cell reconstitution and new anti-HCMV drug therapy for HCMV reactivation after HSCT.
| S-EPMC6546901 | biostudies-literature