Search Results (22)

Background: Gut health is often disrupted in adults with haematological malignancies (HMs) receiving chemotherapy and haematopoietic stem cell transplantation (HCT). Microbial diversity is reduced, and both infection risk and inflammation increased. The role of dietary fibre in enhancing gut health, immune regulation, reducing complications, and improving clinical outcomes for people with HMs shows promise but the extent of their role remains unclear. Objectives: This systematic review evaluated the role of dietary fibre supplementation in adults with HMs undergoing HCT on gut health, immune function, and gastrointestinal health. This included assessment of differences between fibre types. Methods: A systematic search of PubMed and EMBASE was conducted following PRISMA guidelines, independently by two reviewers. Study quality was assessed using the Newcastle–Ottawa scale (NOS). Results: Of the 5023 studies after de-duplication, 63 remained after abstract and title screening, 59 studies were full-text screened, 56 studies were excluded due to language (n = 6), wrong intervention (n = 25), wrong population (n = 4), or reporting on unrelated outcomes (n = 21), and 3 studies met all inclusion criteria. Interventions included fructooligosaccharides (FOS), resistant starch (RS), and a glutamine, fibre, and oligosaccharide (GFO) prebiotic blend. Despite heterogeneity in measured outcomes, positive impacts on gut health, immune function, and gastrointestinal health were shown. Conclusions: Fibre supplementation represents a promising adjunctive strategy to improve clinical outcomes in adults with HMs undergoing HCT, by improving microbial diversity, increasing short-chain fatty acid (SCFA) production, and reducing incidence of acute GVHD. Further research is needed to establish specific recommendations for fibre in the nutritional management of patients with HM. Full article

Background: Sarcina ventriculi is a bacterium predominantly reported in the stomach and associated with emphysematous gastritis, delayed gastric emptying, gastroparesis, or gastric outlet obstruction. Its prevalence is increasing among patients with a history of organ transplants, immunosuppression, and graft-versus-host disease (GVHD). This bacterium can be detected on histology with characteristic tetrad packet morphology; however, confirmation requires PCR and molecular studies. The role of Sarcina ventriculi in human diseases is not fully understood and has unclear clinical significance. While certain studies point to a possible pathogenic role, others regard its detection as incidental with no clear clinical consequence. Case presentation: Herein, we report a case of a 39-year-old male patient with primary refractory cHL, stage IVb, who underwent an autologous bone marrow transplant (BMT) and an allogeneic stem cell infusion. His post-transplant course was complicated by chronic kidney disease (CKD), malnutrition, depression, myopathy, skin, and colon GVHD. He eventually developed sepsis, was admitted to the ICU and developed multiorgan failure and passed away. The patient developed diarrhea, and the gastrointestinal specialist was consulted and revealed ulcerated ileitis and colitis. Biopsies were taken to evaluate for CMV infection and GVHD. The terminal ileum biopsy mainly revealed ulceration with granulation tissue formation and abundant microorganisms arranged in distinctive tetrads, characteristic of Sarcina ventriculi. The colonic biopsies were consistent with GVHD grade II. Conclusions: The significance of Sarcina microorganisms and their mechanisms of injury remain poorly understood. The identification of Sarcina ventriculi in the terminal ileum, which is an unusual and previously unreported finding, adds a new perspective to our understanding of its pathogenic potential and anatomical distribution. While the patient’s clinical decline was influenced by multiple factors, including GVHD, recurrent sepsis, and multiorgan failure, the role of Sarcina ventriculi as a potential exacerbating factor remains unclear. Full article

Gastrointestinal graft-versus-host disease (GvHD) is a frequent and severe complication after allogeneic stem cell transplantation (aSCTx). Although biopsy and histopathology remain the gold standard for diagnosis of GvHD, this approach can be limited by thrombocytopenia accompanying aSCTx and the diagnostic delay associated with routine histopathology. Here, we report on two patients in which dye-based contact microscopy using a latest generation endocytoscope with 520-fold magnification enabled in vivo diagnosis of GvHD. The first patient was a 23-year-old man with acute lymphoblastic leukemia presenting with non-bloody diarrhea 3 months after aSCTx. After topical staining with crystal violet and methylene blue, endocytoscopy in the rectum showed several apoptotic epithelial cells. Histopathology confirmed GvHD grade III according to the Lerner classification. The second patient was a 59-year-old female with diarrhea 3 months after aSCTx. Apart from pathognomic apoptotic bodies, EC additionally revealed crypt lumina enlargement and mononuclear cell infiltrates in the lamina propria with subsequent crypt distension. The duration of the procedure was less than 5 min in each patient. These findings illustrate that in vivo microscopy using endocytoscopy can enable instantaneous diagnosis of GvHD with the benefit of accelerating therapeutic decisions in patients with suspected severe GvHD. Full article

The gut microbiome plays a crucial role in modulating the efficacy and toxicity of cancer therapies, particularly in hematological malignancies. This review examines the dynamic interplay between gut microbiota and cancer treatments, such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT). Disruptions in the gut microbiome, known as dysbiosis, are associated with adverse effects like gastrointestinal toxicity, neutropenia and cardiotoxicity during chemotherapy. Conversely, the supplementation of probiotics has shown potential in mitigating these side effects by enhancing gut barrier function and regulating immune responses. In HSCT, a higher diversity of gut microbiota is linked to better patient outcomes, including reduced graft-versus-host disease (GVHD) and improved survival rates. The microbiome also influences the efficacy of immunotherapies, such as immune checkpoint inhibitors and CAR-T cell therapy, by modulating immune pathways. Research suggests that certain bacteria, including Bifidobacterium and Akkermansia muciniphila, enhance therapeutic responses by promoting immune activation. Given these findings, modulating the gut microbiome could represent a novel strategy for improving cancer treatment outcomes. The growing understanding of the microbiome’s impact on cancer therapy underscores its potential as a target for personalized medicine and offers new opportunities to optimize treatment efficacy while minimizing toxic side effects. Full article

Hematopoietic stem cell transplantation is one of the most intricate immune therapies used for patients with hematological diseases or immune disorders. In addition to the inherent immunosuppression from their primary condition, many of these patients usually receive cytotoxic chemotherapy, radiation therapy, broad-spectrum antibiotics, or experience extended nutritional perturbations. These factors collectively lead to inflammation and the disruption of gut microbiota. Additionally, about 40–60% of patients undergoing fully HLA-matched allogeneic transplantation are expected to develop acute graft-versus-host disease (aGVHD), even with prophylactic measures such as calcineurin inhibitors, methotrexate/mycophenolate, or post-transplant cyclophosphamide treatment. Recent research has elucidated the complex interplay between immune effectors in the gastrointestinal tract and microbial populations within a proinflammatory peri-transplant environment, revealing its significant effect on survival and post-transplant complications such as aGVHD. This review will explore the relationship between dysbiosis during allogeneic transplantation and mechanisms that can help clarify the link between gut microbiota and the risk of GVHD, along with emerging therapeutic strategies aimed at addressing dysbiosis during hematopoietic stem cell transplantation. Full article

Chronic graft-versus-host disease (cGVHD) is a prognostically negative event following hematopoietic stem cell transplant (HSCT). While cGVHD mainly affects the muscles, skin, oral mucosa, eyes, lungs, gastrointestinal tract, and liver, central nervous system (CNS) involvement remains possible and, moreover, is rare when it occurs isolated. CNS-cGVHD can manifest with a wide spectrum of CNS disorders, including cerebrovascular diseases, autoimmune demyelinating diseases, and immune-mediated encephalitis. We present a case of 65-year-old man previously treated with HSCT presenting with progressive cerebrovascular disorder and optic neuropathy without any clear alternative causal processes except for immune-mediated CNS microangiopathy in the context of possible CNS-cGVHD, along with suggestive imaging and instrumental and laboratory findings. Starting one year after HSCT for acute myeloid leukemia, when the first cerebral ischemic event occurred and was then associated with a reduction in visual acuity, an extensive diagnostic work-up had remained inconclusive over many years, leading us to the hypothesis of CNS-cGVHD and, therefore, to the start of immunosuppressive therapy. Our experience highlighted not ignoring the possibility of cGVHD as the underlying mechanism of CNS disorder, even in the absence of other systemic presentations, once more common etiologies of CNS pathological processes have been ruled out. Full article

The gut microbiome significantly influences the outcomes of pediatric leukemia, particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Dysbiosis, caused by chemotherapy, antibiotics, and immune system changes, contributes to complications such as graft-versus-host disease (GVHD), gastrointestinal issues, and infections. Various microbiome-related interventions, including prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT), have shown potential in mitigating these complications. Specific microbial signatures have been linked to GVHD risk, and interventions like inulin, Lactobacillus, and SCFAs (short-chain fatty acids), particularly butyrate, may help modulate the immune system and improve outcomes. FMT, while showing promising results in restoring microbial balance and alleviating GVHD, still requires careful monitoring due to potential risks in immunocompromised patients. Despite positive findings, more research is needed to optimize microbiome-based therapies and ensure their safety and efficacy in pediatric leukemia care. Full article

Background/Objectives: Gastrointestinal diseases are a major cause of morbidity in common variable immunodeficiency disorder (CVID), clinically often mimicking other conditions including celiac disease and inflammatory bowel disease (IBD). Hence, diagnosis of CVID remains challenging. This study aims to raise awareness and highlight histopathological clues for CVID in intestinal biopsies, emphasizing diagnostic pitfalls for the pathologist/gastroenterologist. Methods: We reviewed 63 (18 duodenal, 23 ileal, 22 colonic) biopsies and case histories from seven CVID patients, obtained over a 31-year period, with attention to active inflammation, intraepithelial lymphocytes, plasma cells, lymphoid hyperplasia, crypt/villous architecture, subepithelial collagen, apoptosis, granulomas, and infections. Clinical information of 41 pathology requests was reviewed. Results: Gastrointestinal symptoms were variable. Histological features included IBD-like (3/7), celiac disease-like (2/7), graft-versus-host disease (GVHD)-like (2/7), lymphocytic sprue/colitis-like (3/7), collagenous colitis-like (2/7), and acute colitis-like (4/7) patterns, often overlapping (2/7) and/or changing over time (3/7). Lymphoid hyperplasia was seen in 3/7 patients; 1/7 had giardiasis; and 5/7 had few plasma cells, usually only in part of the gut (3/5). Clinical information of 12/41 (29%) pathology requests mentioned known/suspected CVID, despite being known in 33/41 (80%). Conclusions: Clinical/histological features of CVID in the gut are diverse, often mimicking IBD, microscopic colitis, celiac disease and/or GVHD, hence the importance of adequate clinical information. Some histological features are atypical of these established entities and may indicate CVID, as may overlapping/changing histological patterns and/or few plasma cells in part of the gut. Awareness of the heterogenous clinical presentation and histopathological indicators of CVID may improve diagnosis. Full article

Acute gastrointestinal graft-versus-host disease (GI aGVHD) is a significant and life-threatening complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). Early diagnosis of GI aGVHD is crucial for improving patient outcomes, but it remains a challenge due to the condition’s nonspecific symptoms and the reliance on invasive diagnostic methods, such as biopsies and endoscopic procedures. In recent years, interest in non-invasive diagnostic techniques for graft-versus-host disease has increased, with contrast-enhanced ultrasound (CEUS) being one of them. For this reason, we aimed to examine the potential of ultrasound as a non-invasive, safe, and cost-effective alternative for the early detection and monitoring of GI aGVHD in this review. Our narrative review aims to describe the use of multimodal US that includes conventional US (B-mode and Doppler US) and advanced ultrasound techniques such as CEUS and CRTE for the non-invasive diagnosis of GI GVHD. We browsed several databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search spanned 2000 to the present, focusing on articles written in English that reviewed the use of these imaging techniques in the context of GI GVHD. Following our research, we noticed that CEUS offers several advantages, including the real-time visualization of the gastrointestinal wall, assessment of blood flow, and detailed microvascular analysis—all achieved without the use of ionizing radiation. This feature makes CEUS an appealing option for repeated assessments, which are often necessary in monitoring the progression of GI aGVHD. When used in conjunction with conventional gastrointestinal ultrasound (GIUS), CEUS provides a more comprehensive view of the structural and functional changes occurring in the GI tract, potentially enhancing diagnostic accuracy and allowing for earlier intervention. In comparison to traditional diagnostic methods like tissue biopsy or CT scans, CEUS is less invasive, quicker to perform, and better tolerated by patients, especially those in fragile health following allo-SCT. Its non-invasive nature and ability to provide immediate imaging results make it a valuable tool for clinicians, particularly in settings where minimizing patient discomfort and risk is paramount. However, despite these advantages, there are still gaps in the literature regarding CEUS’s full diagnostic accuracy for GI aGVHD. Further research, including larger clinical trials and comparative studies, is needed to validate CEUS’s role in routine clinical practice and to establish standardized protocols for its use. Nonetheless, CEUS shows considerable potential to transform the diagnostic approach to GI aGVHD by improving early detection, reducing the need for invasive procedures, and ultimately enhancing treatment outcomes for affected patients. Full article

Graft-versus-host disease (GVHD) is an expected and relatively common complication after allogeneic hematopoietic stem cell transplantation. It may affect different organs and typically involves the skin, liver, and gastrointestinal tract (GI-GVHD). GI-GVHD may show heterogeneous presentations with peculiar diagnostic implications. Although an endoscopic biopsy is considered the “gold standard” for the diagnosis of GI-GVHD, its broad application is limited due to the poor clinical conditions usually present in these patients, including thrombocytopenia. In the emergency department, enhanced computed tomography (CECT) has emerged as the best imaging modality for the evaluation of GI damage in frail patients. However, the role of CT in the context of either acute or chronic GI-GVHD has not been systematically investigated. Herein, we focus on the radiological features found on CECT in five patients with GI-GVHD confirmed on histology. CECT was performed for the persistence of GI symptoms in three cases (case 1, case 3, and case 4), for small bowel occlusion in one case (case 5), and for acute GI symptoms in one case (case 2). Serpiginous intestinal wall appearance with multisegmental parietal thickness and homogeneous, mucosal, or stratified small bowel enhancement were common features. Colic involvement with segmental or diffuse parietal thickness was also present. One patient (case 5) presented with inflammatory jejunal multisegmental stenosis with sub-occlusion as a chronic presentation of GI-GVHD. Regarding mesenterial findings, all five patients presented comb signs in the absence of lymphadenopathy. Extraintestinal findings included biliary tract dilatation in two cases (case 2 and case 4). These data support the utility of appropriate radiological investigation in GI-GVHD, paving the way for further serial and systematic investigations to track the appearance and evolution of GI damage in GVHD patients. Full article

This systematic review and meta-analysis aims to identify the outcomes of stem cell transplant (SCT) patients during the COVID-19 era. Pooled event rates (PER) were calculated, and meta-regression was performed. A random effects model was utilized. In total, 36 eligible studies were included out of 290. The PER of COVID-19-related deaths and COVID-19-related hospital admissions were 21.1% and 55.2%, respectively. The PER of the use of hydroxychloroquine was 53.27%, of the receipt of immunosuppression it was 39.4%, and of the use of antivirals, antibiotics, and steroids it was 71.61%, 37.94%, and 18.46%, respectively. The PER of the time elapsed until COVID-19 infection after SCT of more than 6 months was 85.3%. The PER of fever, respiratory symptoms, and gastrointestinal symptoms were 70.9, 76.1, and 19.3%, respectively. The PER of acute and chronic GvHD were 40.2% and 60.9%, respectively. SCT patients are at a higher risk of severe COVID-19 infection and mortality. The use of dexamethasone improves the survival of hospitalized SCT patients with moderate to severe COVID-19 requiring supplemental oxygen or ventilation. The SCT patient group is a heterogeneous group with varying characteristics. The quality of reporting on these patients when infected with COVID-19 is not uniform and further prospective or registry studies are needed to better guide clinical care in this unique setting. Full article

Haematopoietic stem cell transplantation (HSCT) is a treatment option for many haematological conditions in patients of all ages. Nutritional support is important at each stage of treatment, but particular nutritional needs and dictated support occur during the preparatory (conditioning regimen) and post-transplant periods. Patients may require nutritional treatment by the enteral or parenteral route. The quantitative and qualitative composition of meals may change. Vitamin requirements, including vitamin D and vitamin C, might also be different. An adequately composed diet, adapted to the needs of the patient, may influence the occurrence of complications such as graft-versus-host disease (GvHD), gastrointestinal disorders, infections, and reduced survival time. Haematological diseases as well as transplantation can negatively affect the intestinal flora, with negative consequences in the form of mucosal inflammation and disorders of a functional nature. Currently, aspects related to nutrition are crucial in the care of patients after HSCT, and numerous studies, including randomized trials on these aspects, are being conducted. This study serves the critical analysis of current scientific evidence regarding nutritional support for patients after HSCT. Full article

The high serum concentrations of TNF-α characterize acute graft-versus-host disease (aGVHD), for which infliximab treatment may be beneficial. In 28 pediatric patients, four doses of 10 mg/kg infliximab every seven days were administered after steroid failure (Standard Group, n = 14) or as a first-line therapy (Early Group, n = 14). Population pharmacokinetic analyses and evaluation of serum cytokines were performed. After two months of treatment, complete response in gastrointestinal and liver aGVHD was achieved in 43% and 100% of patients in the Standard and Early groups, respectively. During follow-up, four patients in the Standard Group (but none in the Early Group) experienced an aGVHD recurrence. Viral infections occurred more frequently in the Standard Group after the fifth dose. Infliximab clearance did not differ between groups or according to treatment outcome for each organ involved in aGVHD, whereas serum levels of cytokines significantly differed. Therefore, present findings show that use of first-line, TDM-driven infliximab to treat aGVHD in children may result in better clinical outcomes and tolerability, with a different pattern of cytokines generated according to the moment of beginning of treatment. Full article

Graft versus host disease (GVHD) is one of the most serious complications following stem cell transplant in children and is a major cause of morbidity and mortality. Corticosteroids remain the mainstay of treatment, and although a majority of children respond to systemic steroids, those refractory to or dependent upon corticosteroids suffer from complications secondary to long-term steroid administration. This problem has prompted consideration of steroid-sparing treatment strategies, although the time to clinical remission can be variable. Intraarterial corticosteroid delivery has been used in adults as a rescue therapy in steroid-resistant patients, but its use in children has been limited. We investigated the feasibility of intraarterial steroid administration into the bowel and/or liver in a cohort of six pediatric patients with acute GVHD. All patients successfully underwent treatment with no serious adverse effects. Five of five (100%) patients with gastrointestinal bleeding due to GVHD had rapid symptom improvement by 48 h, which was durable up to three weeks. Three of four (75%) patients with hepatic GVHD had improved cholestasis following intraarterial steroid administration. Our experience with this small cohort preliminarily demonstrated the feasibility and safety of intraarterial steroid administration in children with acute GVHD. This approach warrants consideration as a rescue therapy in steroid-refractory cases and as a “bridge” therapy for children with severe acute GVHD who are transitioning to steroid-sparing regimens. Full article

Musculoskeletal graft versus host disease (GVHD) is a rare manifestation of chronic GVHD (cGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Left untreated, the disease can cause extensive damage to muscle tissue and joints. We describe a 62-year-old male with musculoskeletal GVHD and generalized muscle pain and stiffness. In addition, we performed a systemic literature review based on published cases of musculoskeletal GVHD between 1983 and 2019. We identified 85 cases, 62% male and 38% female with an age of 4–69 years and median age of 39 years at diagnosis. The majority of patients (72%) also had manifestations of cGVHD in at least one other organ system, most frequently the skin (52%), followed by oropharyngeal mucosa (37%), and pulmonary and gastrointestinal tract (GI tract) (21%). We conclude that, while musculoskeletal cGVHD is a rare complication of allo-HSCT, it remains a serious and debilitating risk that must be considered in patients with muscle pain, muscle weakness, joint stiffness, and tissue inflammation. Early intervention is critical for the patient’s prognosis. Full article