Search Results (31)

Objectives: The aim of this study was to evaluate the oral health-related quality of life of patients with chronic graft-versus-host disease. Methods: A total of 22 patients with graft-versus-host disease aged 45.05 ± 14.66 years were enrolled in a single-centre cross-sectional study. Data from questionnaires on general health and diet, clinical examinations, and salivary tests were used to assess caries risks using the Cariogram computer programme. The Slovenian version of the Oral Health Impact Profile Questionnaire (OHIP-SVN) was used to determine the oral health-related quality of life. Results: Compared to healthy individuals, patients with chronic graft-versus-host disease had a lower oral health-related quality of life and a lower stimulated salivary flow rate (in both cases p < 0.001). The OHIP summary score correlated with stimulated salivary pH (R = 0.4916, p = 0.0277) and caries risk (R = 0.5420, p = 0.0111). Conclusions: In conclusion, our results confirm that cGVHD has a negative impact on oral health-related quality of life due to lower stimulated salivary pH and elevated caries risk (reduced salivary pH, flow rate, buffering capacity, and elevated Streptococcus mutans and Lactobacillus bacteria count). These findings emphasise the importance of a comprehensive assessment of oral health and preventive care in patients with cGVHD and suggest that the integration of clinical and quality of life measures could lead to improved patient care strategies. 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

Background/Objectives: Chronic graft-versus-host disease (cGVHD) and oral lichen planus (LPO) are chronic inflammatory conditions with similar oral manifestations. This study aimed to assess whether serum and salivary cytokines (IL-1α, IL-6, IL-17) could serve as reliable biomarkers for cGVHD. Methods: A prospective cohort study was conducted involving cGVHD patients, LPO patients, and healthy controls. Cytokine levels in serum and saliva were measured by ELISA and compared across the groups using the Kruskal–Wallis test. Results: IL-17 levels were significantly elevated in the serum of cGVHD patients compared to LPO patients and controls (p < 0.05). However, IL-6 and IL-1α did not show significant differences among the groups. A comparison of salivary samples between the three groups did not reach statistical significance (p > 0.05). Conclusions: This study suggests that IL-17 could be a potential biomarker for cGVHD-related inflammation, warranting further investigation. Salivary samples do not seem to be a reliable biological marker for the diagnosis of cGVHD. The findings underline the need for larger studies to validate these preliminary results. Full article

Chronic graft-versus-host disease (cGvHD) is a multisystem disorder that occurs in recipients of allogeneic hematopoietic (alloHCT) stem cell transplants and is characterized by both inflammatory and fibrotic manifestations. It begins with the recognition of host tissues by the non-self (allogeneic) graft and progresses to tissue inflammation, organ dysfunction and fibrosis throughout the body. Oral cavity manifestations of cGVHD include mucosal features, salivary gland dysfunction and fibrosis. This review synthesizes current knowledge on the pathogenesis, diagnosis and management of oral cGVHD, with a focus on emerging trends and novel therapeutics. Data from various clinical studies and expert consensus are integrated to provide a comprehensive overview. Full article

Background/Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) resulting from histocompatibility differences between donor and host cells leading to inflammation, tissue damage, and compromised patient outcome. Extracorporeal photopheresis (ECP) is considered as a second-line treatment administered to patients with GVHD who do not respond to corticosteroid treatment or who experience a relapse after an initial response and are therefore classified as steroid refractory (SR). The aim of this study is to evaluate the clinical response rates in both pediatric and adult patients with acute (a) or chronic (c) GVHD and to assess the effectiveness of ECP using the real-world data from a single center. Methods: We performed a retrospective study on 30 patients, including 11 pediatric and 19 adult patients who were treated with ECP as a second-, third-, or fourth-line therapy for (a) and (c) GVHD, alongside corticosteroids and other immunomodulatory medications. The median time from aGVHD onset to ECP was 11.5 days (range: 3 days–9 months), while for cGVHD, the median time was 90 days (range: 2 days–9 months). Results: The overall response rate (ORR) in the aGVHD patient population was 60% with a median of 9 procedures (range: 2–20). For cGVHD patients, the ORR was 70% after a median of 23.5 ECP procedures (range: 8–43). Most patients had skin involvement, with ECP achieving an ORR of 81.8% in aGVHD and 77.7% in cGVHD cases. Conclusions: ECP is a beneficial therapy for patients with (a) and (c) GVHD who have not responded to corticosteroids and other forms of immunosuppressive therapy. Specifically, ECP demonstrated efficacy in improving skin and oral symptoms and permitted reductions in or the elimination of their corticosteroid usage. The study found that extending the duration of ECP treatment was associated with better outcomes, and no detectable complications were observed over a 38-week period. Full article

Background and Objectives: Lichen planus of the lip (LPL) is a chronic inflammatory condition that resembles actinic cheilitis, discoid lupus erythematosus, graft-versus-host disease, and lichenoid reaction to dental materials or drugs. The purpose of this study was to conduct a literature review on lichen planus lip involvement and to report a retrospective observational study that characterises and explores the clinical, histopathological, and evolution of the lesions in a group of patients with unique involvement of LPL. Materials and Methods: Clinical data of patients diagnosed with LPL was retrieved from the medical charts of the patients referred to the Oral Pathology Department of the “Carol Davila” University of Medicine and Pharmacy. A concurrent electronic literature research was carried out using PubMed and Web of Science from 2003 to 2023. Results: Eleven patients diagnosed with unique LPL were analysed (male/female ratio was 1.75, mean age 63.64 years ± 12.52). All patients presented lesions of the lower lip; the clinical forms were atrophic (six cases) and erosive (five cases), and the histopathological exam confirmed the diagnosis. After topical treatment with corticosteroids, most of the patients had complete remission. The literature review revealed 24 studies (sixteen case reports and eight case series) which comprised 84 patients. Isolated lip involvement was reported in 17 studies, and five articles with concomitant oral lichen planus, while two articles did not mention this criterion. Conclusions: Our study brings new data on isolated lichen planus of the lip that primarily affects the lower lip with predominance in male patients. It was reported worldwide in patients between 22 and 75 years old. Topical corticosteroids were the main treatment prescribed and they usually brought remission of the lesions. Lichen planus of the lip is a challenging diagnosis for oral health practitioner providers as well as for dermatologists. Full article

A crucial complication after allogeneic hematopoietic cell transplantation (alloHCT), namely, acute graft-versus-host disease (aGVHD), occurs in about 50% of transplant recipients, leading to high morbidity and mortality. Thus far, the diagnosis of GVHD has been mainly established through clinical features and histologic or laboratory evidence of periductal lymphocyte infiltration, fibroplasia, and mixed lymphocytic and plasmocytic inflammation. Intensive research is focused on identifying biomarkers for the early diagnosis, prediction of disease, response to treatment, prognosis, and risk stratification of patients. The serum biomolecules that have been investigated are reported and summarized. Moreover, oral tissue involvement in GVHD is described, and other biomarkers that have been proposed, such as saliva, are analyzed. Future research is highlighted as a necessity in order for these biomarkers to be validated and quantified for use in clinical practice. Full article

Mycophenolate mofetil (MMF) is commonly used for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, limited population pharmacokinetic (PPK) data are available for pediatric HSCT patients. This study aimed to develop a PPK model and recommend optimal oral MMF dosage in pediatric HSCT patients. This prospective study involved pediatric HSCT patients at a tertiary academic institution. Patients received oral MMF 15–20 mg/kg twice daily for aGVHD prophylaxis and treatment. The PPK analysis was conducted using a nonlinear mixed-effects modeling method. Simulation was performed considering different body surface areas (BSAs) (0.5 m², 1.0 m², 1.5 m²) and dosing (400 mg/m², 600 mg/m², 900 mg/m² twice daily). Based on the simulation, an optimal dosage of oral MMF was suggested. A total of 20 patients and 80 samples were included in the PPK model development. A one-compartment model with first-order absorption adequately described the pharmacokinetics of mycophenolic acid (MPA). BSA was a statistically significant covariate on V_d/F. Simulation suggested the optimal dosage of oral MMF as 900 mg/m² twice daily, respectively. A reliable PPK model was developed with good predictive performance. This model-informed optimal MMF dosage in pediatric HSCT patients can provide valuable dosing guidance in real-world clinical practice. Full article

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation (HSCT). GVHD may also develop following solid transplants or blood transfusions if white blood cells are transferred. GVHD affects multiple organs, including the oral tissues. This pictorial review provides a background of GVHD to dental practitioners, describes the most common oral manifestations of GVHD, and highlights the main treatment modifications needed to deliver dental care to patients with GVHD. A narrative review enriched with clinical data was performed by searching the scientific literature for all articles regarding GVHD and oral manifestations/therapies. All articles without exclusion criteria, except animal tests, were included in the above review. Acute GVHD may manifest in the oral mucosa; however, it often develops immediately following HSCT when routine dental treatment is postponed. Chronic GVHD may manifest in the oral mucosa, the salivary glands, and the musculoskeletal compartment. It may indirectly affect the teeth and the oral flora, putting the patient at risk for infections. Importantly, GVHD poses an increased risk for oral cancer. GVHD has a wide range of oral manifestations, some of which may affect dental treatment. Full article

Graft-versus-host disease (GvHD) is a common and severe complication following allogeneic hematopoietic stem cell transplantation (HSCT). Its prevention and treatment is a major challenge. Ferulic acid (FA) has anti-inflammatory and antioxidant properties that could be attractive in this setting. Our aim was to evaluate a bioactive ingredient derived from wheat bran (WB), selected for its high concentration of FA, in a murine model of GvHD. The ingredient was obtained via a bioprocess involving hydrolysis and spray-drying. GvHD was induced via HSCT between MHC-mismatched mouse strains. FA treatment was administered orally. Survival and disease scores (weight loss, hunching, activity, fur texture, and skin integrity, each scored between 0 and 2 depending on disease severity) were recorded daily, histological evaluation was performed at the end of the experiment, and serum inflammatory cytokines were analyzed on days 9 and 28. Treatment with FA did not protect GvHD mice from death, nor did it diminish GvHD scores. However, histological analysis showed that ulcers with large areas of inflammatory cells, vessels, and keratin were less common in skin samples from FA-treated mice. Areas of intense inflammatory response were also seen in fewer small intestine samples from treated mice. In addition, a slight decrease in INF-γ and TNF-α expression was observed in the serum of treated mice on day 28. The results showed some local effect of the ingredient intervention, but that the dose used may not be sufficient to control or reduce the inflammatory response at the systemic level in mice with GvHD. Higher dosages of FA may have an impact when evaluating the immunomodulatory capabilities of the hydrolyzed WB ingredient. Thus, further experiments and the use of technological strategies that enrich the ingredients in soluble ferulic acid to improve its efficacy in this setting are warranted. Full article

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. We evaluated the safety and efficacy of ibrutinib, alone or combined with standard-of-care regimens, in adults with advanced urothelial carcinoma (UC). Once-daily ibrutinib was administered orally at 840 mg (single-agent or with paclitaxel) or at 560 mg (with pembrolizumab). Phase 1b determined the recommended phase 2 dose (RP2D) of ibrutinib, and phase 2 assessed progression-free survival (PFS), overall response rate (ORR), and safety. Thirty-five, eighteen, and fifty-nine patients received ibrutinib, ibrutinib plus pembrolizumab, and ibrutinib plus paclitaxel at the RP2D, respectively. Safety profiles were consistent with those of the individual agents. The best-confirmed ORRs were 7% (two partial responses) with single-agent ibrutinib and 36% (five partial responses) with ibrutinib plus pembrolizumab. Median PFS was 4.1 months (range, 1.0–37.4+) with ibrutinib plus paclitaxel. The best-confirmed ORR was 26% (two complete responses). In previously treated patients with UC, ORR was higher with ibrutinib plus pembrolizumab than with either agent alone (historical data in the intent-to-treat population). ORR with ibrutinib plus paclitaxel was greater than historical values for single-agent paclitaxel or ibrutinib. These data warrant further evaluation of ibrutinib combinations in UC. Full article

Immunotherapy with immune checkpoint inhibitors (ICIs) nowadays has indications for several solid tumors. The current targets for ICIs are CTLA-4, PD-1, and PD-L1 receptors. Despite the clinical advantages derived from ICIs, a variety of side effects are linked to overstimulation of the immune system. Among these, ICI-related colitis is one of the most common, with a disabling impact on the patient. Diarrhea, abdominal pain, abdominal distension, cramping, and hematochezia are the most common ICI enterocolitis presenting symptoms. The most frequently used grading system for assessment of the severity of ICI enterocolitis is called the Common Terminology Criteria for Adverse Events (CTCAE) grading. With regard to the histological picture, there is no specific feature; however, microscopic damage can be classified into five types: (1) acute active colitis, (2) chronic active colitis, (3) microscopic colitis-like, (4) graft-versus-host disease-like, and (5) other types. Supportive therapy (oral hydration, a bland diet without lactose or caffeine, and anti-diarrheal agents) is indicated in mild colitis. Symptomatic treatment alone or with loperamide, a low-fiber diet, and spasmolytics are recommended for low-grade diarrhea. In more severe cases, corticosteroid treatment is mandatory. In refractory cases, off-label use of biological therapies (infliximab or vedolizumab) was proposed. Full article

Recipients of a haematopoietic stem cell transplantation (HSCT) may experience issues in medication adherence (MA) when discharged. The primary aim of this review was to describe the oral MA prevalence and the tools used to evaluate it among these patients; the secondary aims were to summarise factors affecting medication non-adherence (MNA), interventions promoting MA, and outcomes of MNA. A systematic review (PROSPERO no. CRD42022315298) was performed by searching the Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane Library, Excerpta Medica dataBASE (EMBASE), PsycINFO, PubMed and Scopus databases, and grey literature up to May 2022 by including (a) adult recipients of allogeneic HSCT, taking oral medications up to 4 years after HSCT; (b) primary studies published in any year and written in any language; (c) with an experimental, quasi-experimental, observational, correlational, and cross-sectional design; and (d) with a low risk of bias. We provide a qualitative narrative synthesis of the extracted data. We included 14 studies with 1049 patients. The median prevalence of MA was 61.8% and it has not decreased over time (immunosuppressors 61.5% [range 31.3–88.8%] and non-immunosuppressors 65.2% [range 48–100%]). Subjective measures of MA have been used most frequently (78.6%) to date. Factors affecting MNA are younger age, higher psychosocial risk, distress, daily immunosuppressors, decreased concomitant therapies, and experiencing more side effects. Four studies reported findings about interventions, all led by pharmacists, with positive effects on MA. Two studies showed an association between MNA and chronic graft-versus-host disease. The variability in adherence rates suggests that the issues are relevant and should be carefully considered in daily practice. MNA has a multifactorial nature and thus requires multidisciplinary care models. Full article

Kaposi sarcoma is relatively common after solid organ transplantation, but very rare after hematopoietic stem cell transplant (HSCT). Here we are reporting a rare case of Kaposi sarcoma in a child after HSCT. An 11-year-old boy with Fanconi anemia was treated by haploidentical HSCT from his father. Three weeks after transplantation, the patient developed severe graft-versus-host disease (GVHD) which was treated by immunosuppressive therapy and extracorporeal photopheresis. Approximately 6.5 months after HSCT, the patient had asymptomatic nodular skin lesions over the scalp, chest, and face. Histopathological examination showed typical findings of Kaposi sarcoma. Later, additional lesions in the liver and oral cavity were confirmed. Liver biopsy was positive for HHV-8 antibodies. The patient was continued on Sirolimus which was already being used for the treatment of GVHD. Cutaneous lesions were also treated with topical timolol 0.5% ophthalmic solution. Within six months, cutaneous and mucous membrane lesions were completely resolved. Follow-up abdominal ultrasound and MRI showed the disappearance of the hepatic lesion. Full article

Chronic graft-versus-host disease (cGVHD) is a serious complication after allogenic hematopoietic stem cell transplantation (allo-HSCT), negatively affecting the morbidity and mortality of recipients. Skin involvement is the most common cGVHD manifestation with a wide range of pleomorphic features, from scleroderma to ulcerations and microangiopathic changes. Despite the access to many immunosuppressive drugs, therapy for cGVHD is challenging. Systemic steroids are recommended as the first-line treatment; but, in steroid-resistant patients, extracorporeal photopheresis (ECP) remains one of the subsequent therapeutic options. Here, we present a case report of a 31-year patient suffering from advanced steroid-refractory skin and oral mucosa cGVHD who was spectacularly treated with ECP. It was the first time we observed such “overnight” resolution of the graft-versus-host disease syndrome. The present report proves the important role of ECP in the treatment of steroid-resistant cGVHD, especially when other immunosuppressive therapies have failed. Full article