Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation.
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ABSTRACT:
SUBMITTER: Atilla E
PROVIDER: S-EPMC5451667 | biostudies-other | 2017 Mar
REPOSITORIES: biostudies-other
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Project description:The gastrointestinal (GI) system is one of the most commonly affected sites during a hematopoietic stem cell transplantation (HSCT) due to toxicities of preparative regimens, the accompanying immunodeficiency, and organ damage caused by graft versus host disease. In this review, we focus on early GI and liver complications following autologous (auto-) and allogeneic (allo-) HSCT and clarify both the risk factors and therapeutic strategies. Early GI and liver complications associated with HSCT remain challenging issues. Despite the improvements in this field during the last decade, treatments for these complications still place a significant burden on both patients and the physicians treating these patients. GI and liver complications remain some of the causes of mortality associated with HSCT. For practicing hematologists, oncologists, and gastroenterologists in this field, the awareness and early diagnosis of the GI complications remain important factors to obtain optimal outcomes in this patient population.
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Project description:A growing body of evidence suggests that iron overload is associated with inferior outcomes after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). However, all of those studies used surrogate markers of iron overload, especially serum ferritin, and most had a retrospective design. We conducted a prospective observational study in patients with myelodysplastic syndrome or acute leukemia undergoing myeloablative HSCT. Forty-five patients who were followed for over 1 year, with serial measurements of serum iron parameters, as well as liver and cardiac magnetic resonance imaging. There was no significant increase in ferritin, liver or cardiac iron content in the 12 months following HSCT. Although serum ferritin still appeared to have prognostic significance, as previously reported, pre-HSCT iron overload (as reflected in liver iron content) was not associated with increased mortality, relapse, or graft-versus-host disease. These results raise the possibility that the adverse prognostic impact of pre-HSCT hyperferritinemia may be related to factors independent of iron overload.
| S-EPMC3358569 | 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: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
Project description:Patients with hematologic malignancies undergoing allogeneic stem cell transplantation (HSCT) commonly have an elevated serum ferritin prior to HSCT, which has been associated with increased mortality after transplantation. This has led to the suggestion that iron overload is common and deleterious in this patient population. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. We report a prospective study of 48 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS) undergoing myeloablative HSCT, using magnetic resonance imaging (MRI) to estimate liver iron content (LIC) and cardiac iron. The median (and range) pre-HSCT value of serum ferritin was 1549 ng/mL (20-6989); serum hepcidin, 59 ng/mL (10-468); labile plasma iron, 0 LPI units (0.0-0.9). Eighty-five percent of patients had hepatic iron overload (HIO), and 42% had significant HIO (LIC ≥5.0 mg/gdw). Only 1 patient had cardiac iron overload. There was a strong correlation between pre-HSCT serum ferritin and estimated LIC (r = .75), which was mostly dependent on prior transfusion history. Serum hepcidin was appropriately elevated in patients with HIO. Labile plasma iron elevation was rare. A regression calibration analysis supported the hypothesis that elevated pre-HSCT LIC is significantly associated with inferior post-HSCT survival. These results contribute to our understanding of the prevalence, mechanism, and consequences of iron overload in HSCT.
| S-EPMC3954514 | biostudies-literature
Project description:Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation (HSCT) in children. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare the whole genome expression in children before and after HSCT. A total of 33 children referred for HSCT were enrolled in the study. In 70% of the patients HSCT was performed for the treatment of neoplasms. Blood samples were obtained before HSCT and six months after the procedure. Subsequently, the whole genome expression was assessed in leukocytes using GeneChip Human Gene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed altered expression of 124 genes. Pathway enrichment analysis revealed upregulation of five pathways after HSCT: allograft rejection, graft-versus-host disease, type I diabetes mellitus, autoimmune thyroid disease, and viral myocarditis. The activation of those pathways seems to be related to immune reactions commonly observed after HSCT. Our results contribute to better understanding of the genomic background of the immunologic complications of HSCT.
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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: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.
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Project description:The proteasome and its associated ubiquitin protein modification system have proved to be an important therapeutic target in the treatment of multiple myeloma and other cancers. In addition to direct antitumor effects, proteasome inhibition also exerts strong effects on nonneoplastic immune cells. This indicates that proteasome inhibition, through the use of agents like bortezomib, could be used therapeutically to modulate immune responses. In this review we explore the emerging data, both preclinical and clinical, highlighting the importance of proteasome targeting of immunologic responses, primarily in the context of allogeneic hematopoietic stem cell transplantation (HSCT), both for the control of transplant-related toxicities like acute and chronic graft-versus-host disease (aGVHD, cGHVHD), and for improved malignant disease control after allogeneic HSCT.
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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.
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