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Hepatic ductopenia is a pathologic diagnosis characterized by a decrease in the number of intrahepatic bile ducts as a consequence of various underlying etiologies. Some etiologies, such as primary sclerosing cholangitis, primary biliary cholangitis, and ischemic cholangitis, often have distinctive imaging findings. In contrast, other causes such as chronic rejection following liver transplantation, drug-induced biliary injury, infection, malignancy such as lymphoma, and graft-versus-host disease may only have ancillary or non-specific imaging findings. Thus, diagnosing ductopenia in conditions with nonspecific imaging findings requires a multidimensional approach, including clinical evaluation, serological testing, imaging, and liver histology to identify the underlying cause. These etiologies lead to impaired bile flow, resulting in cholestasis, liver dysfunction, and, ultimately, cirrhosis and liver failure if the underlying cause remains untreated or undetected. In the majority of instances, individuals diagnosed with ductopenia exhibit a positive response to treatment addressing the root cause or cessation of the causative agent. This article focuses on acquired causes of ductopenia, its clinical manifestation, histopathology, imaging diagnosis, and management. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) is a highly effective therapy for malignant blood illnesses that pose a high risk, as well as diseases that are at risk due to other variables, such as genetics. However, the prevalence of graft-versus-host disease (GVHD) has impeded its widespread use. Ensuring the stability of microbial varieties and associated metabolites is crucial for supporting metabolic processes, preventing pathogen intrusion, and modulating the immune system. Consequently, it significantly affects the overall well-being and susceptibility of the host to disease. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may experience a disruption in the balance between the immune system and gut bacteria when treated with medicines and foreign cells. This can lead to secondary intestinal inflammation and GVHD. Thus, GM is both a reliable indicator of post-transplant mortality and a means of enhancing GVHD prevention and treatment after allo-HSCT. This can be achieved through various strategies, including nutritional support, probiotics, selective use of antibiotics, and fecal microbiota transplantation (FMT) to target gut microbes. This review examines research advancements and the practical use of intestinal bacteria in GVHD following allo-HSCT. These findings may offer novel insights into the prevention and treatment of GVHD after allo-HSCT. Highlights: Hematopoietic stem cell transplantation (HSCT) is a powerful treatment for high-risk blood diseases and genetic disorders. Graft-versus-host disease (GVHD) remains a major obstacle to the broader application of HSCT. Maintaining a stable gut microbiome is crucial for supporting metabolism, preventing infections, and regulating the immune system. Allogeneic HSCT can disrupt the gut-immune balance, causing inflammation and triggering GVHD. Innovative strategies like nutritional support, probiotics, selective antibiotics, and fecal microbiota transplantation (FMT) can prevent and treat GVHD post-allo-HSCT. [ABSTRACT FROM AUTHOR]

Although graft‐versus‐host disease (GVHD) is a common complication of hematopoietic stem cell transplantation, it is rare after solid organ transplantation (SOT) or blood transfusion. We present a rare case of SOT‐derived and/or transfusion‐associated graft‐versus‐host disease (TA‐GVHD) in a 66‐year‐old man with interstitial lung disease who underwent bilateral lung transplantation (LT) from a 12‐year‐old female donor and required three units of packed red blood cells intraoperatively. He presented with signs and symptoms consistent with GVHD, and a bone marrow biopsy revealed an XX karyotype. He died 3 months after bilateral LT, and postmortem chimerism testing using next‐generation sequencing identified three sources of DNA within his bone marrow, including the recipient, the lung donor, and a third donor, thereby suggesting the presence of solid organ transplant graft‐versus‐host disease (SOT‐GVHD), TA‐GVHD, or a combination of both. [ABSTRACT FROM AUTHOR]

The principle of immune checkpoint blockade therapy is based on the activation of T cells. Immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1 and anti-CTLA-4 antibodies, have demonstrated effectiveness in treating solid tumors by reinvigorating the immune system to recognize and eliminate malignant cells. In recent years, ICIs have shown promise in certain patients with relapsed or refractory lymphoma and myeloid malignancies. Allogeneic hematopoietic stem cell transplant (allo-HCT) currently remains the only curative immunotherapy option for eligible patients with these hematologic malignancies. An increasing number of patients with indications for allo-HCT have received treatment with ICIs either before the procedure or as a therapy for relapse after allo-HCT. Nevertheless, initial reports suggest that patients exposed to immune checkpoint inhibitors either before or after allo-HCT are at an increased risk of developing severe graft-versus-host disease and other immune-related adverse events, likely due to the persistent effects of immune checkpoint blocking. Maximizing therapeutic benefits while minimizing side effects of the combination of checkpoint blockade immunotherapy and allo-HCT is an active area of research aimed at improving the prognosis of relapsed or refractory hematologic malignancies. However, there is still a lack of rational design strategies to optimize the combined use of these two different types of immunotherapies. In this review, we addressed the scientific rationale behind ICIs for treating lymphoma and myeloid malignancies. We also summarized the evidence supporting the use of ICIs as salvage therapy before and after allo-HCT. Additionally, we offered insights into current approaches for preventing and treating graft-versus-host disease and other immune-related adverse events during the procedure. [ABSTRACT FROM AUTHOR]

Introduction: CAR T-cell therapy is highly effective, but also associated with unique toxicities. Because of the origin of T cells in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT), graft-versus-host disease (GVHD) in the post-CAR T-cell setting poses a relevant concern but is only scarcely studied. Potential risk factors and mitigation strategies (from CAR T-cell modifications to clinical management) are yet to be determined. Methods: Sharing our retrospective experience and a mini-review of the literature, our aim is to better understand the frequency and risk of the potential occurrence of GVHD after CAR T cells, which are most likely underestimated. Results: Here, we present a cohort of 11 patients with symptoms suggestive of GVHD out of 25 allografted patients treated with CAR T cells, of whom 3 patients (12%) had GVHD most likely triggered by the preceding CAR T-cell treatment. Severe chronic pulmonary GVHD occurred in a patient after CD19-directed CAR T-cell therapy. Extracorporeal photopheresis (ECP) mediated successful long-term control of GVHD without causing relapse of the underlying disease. Discussion/Conclusion: In conclusion, CD19-directed CAR T-cell therapy seems to be feasible in patients after alloHCT but might comprise the potential risk of triggering GVHD, most likely depending on the T-cell source, donor compatibility, and the specific CAR construct used. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which often have inadequate response rates requiring next-in-line therapies. Ruxolitinib is commonly used in these cases; however, patients can be ruxolitinib-intolerant or -refractory, necessitating further interventions. Here, we discuss the use of combined cytokine blockade therapy (CCBT) using the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker), which, though often used clinically, have not been adequately explored in the literature. This study evaluated the overall response rate, non-relapse mortality, and overall survival of CCBT in a cohort of steroid-refractory aGvHD patients and finds that CCBT could serve as an acceptable alternative when patients are ruxolitinib-intolerant. Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature. Methods: Sixty patients with steroid-refractory aGVHD were analyzed. The primary objective was to determine the overall response rate (ORR) for CCBT. Secondary outcomes included non-relapse mortality (NRM) and overall survival (OS). Results: ORR for CCBT at day 7, 14, and 28 were 28.3% (17/60; CR 5.0%/PR 23%), 38.3% (23/60; CR 11.3%/PR 27%), and 38.3% (23/60; CR 23.3%/PR 15%), respectively. Patients who received ruxolitinib prior to CCBT had lower ORR (25% CR = 15%/PR = 10%) compared to those who did not (47.5% CR = 27.5%/PR = 20%). In patients with and without ruxolitinib initiated prior to CCBT, NRM at 6 months was 60% (95% CI, 34.5–78) and 47.5% (95% CI, 31–62), while OS at 12 months was 30% (95% CI, 12–50) vs. 40% (95% CI, 25–55), respectively. Conclusions: CCBT has shown potential efficacy in steroid-refractory GI aGvHD, and given the observed ORR when used as second-line therapy, CCBT could serve as an acceptable alternative for patients who are ruxolitinib-intolerant. Ruxolitinib-refractory GI GvHD remains an area of unmet need and CCBT can provide salvage therapy for some patients. [ABSTRACT FROM AUTHOR]

Haploidentical hematopoietic can be conducted on an outpatient basis but the two main reasons to accept into the hospital a patient in this setting are complications of the hematological toxicity and/or the cytokine-release syndrome. With the aim of reducing the post-transplant cyclophosphamide-dependent toxicity without compromising its effectivity, attempts to reduce the dose of post-transplant cyclophosphamide have been made: Decreases from the conventional total dose of post-transplant cyclophosphamide (100 mg/Kg) have been explored worldwide, showing that decreasing the total dose to even 50 mg/Kg significantly decreases the toxicity of the procedure without compromising its efficacy, safety and results. We present here the salient data of the attempts to diminish the doses of post-transplant cyclophosphamide which have been done and published worldwide, information that suggests that the conventional doses of post-transplant cyclophosphamide can be significantly reduced thus decreasing the toxicity, without compromising the effectiveness of the procedure, mainly the development of graft versus host disease. [ABSTRACT FROM AUTHOR]

This retrospective analysis evaluated the use of anti-thymocyte globulin (ATG) with or without post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis in children with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT). The study included 57 children, with 35 in the ATG-PTCy group and 22 in the ATG group. While overall incidence of acute and chronic GvHD did not differ significantly between groups, the ATG-PTCy group had lower rates of grade II-IV acute GvHD (p = 0.013) and moderate-to-severe chronic GvHD (p = 0.001) compared to the ATG group. Importantly, ATG-PTCy significantly improved GvHD/relapse-free survival (GRFS) compared to ATG (65.71% vs. 36.63%; p = 0.003). There were no differences in engraftment, infection rates, immune reconstitution, overall survival, leukemia-free survival, relapse rate, or non-relapse mortality between the two groups. Combining ATG with PTCy may reduce moderate-to-severe GvHD and improve GRFS in children undergoing HSCT for acute leukemia. [ABSTRACT FROM AUTHOR]

Background: Graft‐versus‐host disease (GVHD) is a recognized complication among individuals undergoing bone marrow transplantation (BMT). There is a requirement for supplementary data regarding the in‐patient outcomes of GVHD in individuals who have undergone BMT. Our analysis seeks to assess the healthcare burden and outcomes associated with GVHD in hospitalized patients who have undergone BMT. Method: In this retrospective study, we used data from the National Inpatient Sample (NIS) database spanning from 2016 to 2019. Utilizing ICD‐10 codes, we distinguished hospitalizations related to BMT and grouped them into two categories: those with GVHD and those without GVHD. Our areas of focus included in‐hospital mortality, length of stay, charges, and associations related to GVHD. Unadjusted odds ratios/coefficients were computed through univariable analysis, followed by adjusted odds ratios (aORs)/coefficients from multivariable analysis that considered potential confounding factors. Results: From 2016 to 2019, data were collected from 13,999 hospitalizations with bone marrow transplants. Among them, 836 had GVHD cases. Patient characteristics showed slight differences in mean age and demographics between the two groups, with GVHD patients having a mean age of 51.61 years and higher percentages of males and whites. Analyzing outcomes, patients with GVHD experienced significantly longer hospital stays (41.4 days vs. 21.3 days) and higher total hospital charges ($824,058 vs. $335,765). Adjusting for confounding factors, GVHD posed a substantial risk. The aOR for mortality in GVHD hospitalizations was 7.20 (95% CI: 5.54–9.36, p <.001). The coefficient for the length of stay was 19.36 days (95% CI: 17.29–21.42, p <.001), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889, p <.001) in GVHD cases. Furthermore, GVHD in patients was associated with elevated risks of various medical conditions. The aORs for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in GVHD patients were 2.79 (95% CI: 2.28–3.41, p <.001), 3.30 (95% CI: 2.57–4.24, p <.001), 5.10 (95% CI: 4.01–6.49, p <.001), 4.88 (95% CI: 3.75–6.34, p <.001), 1.45 (95% CI: 1.13–1.86, p =.003), and 3.57 (95% CI: 2.97–4.29, p <.001). Conclusion: GVHD in individuals undergoing BMT is linked to elevated mortality rates, prolonged hospitalization, and higher healthcare costs. Moreover, they face a significantly increased risk of developing complications, such as sepsis, pneumonia, acute respiratory failure, C. difficile infection, and AKI. These results underscore the critical need for vigilant monitoring and effective GVHD management to improve patient outcomes and reduce the complications associated with BMT. Nevertheless, further prospective studies are essential to obtain a more profound understanding and a comprehensive assessment of outcomes in these hospitalized patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: Graft-versus-host disease (GVHD) is a serious complication after allogeneic HCT. Recently, several pivotal studies have been conducted demonstrating significant improvements in the management of GVHD. Here, we review important trials pertaining to GVHD prevention, acute GVHD treatment, and treatment of steroid refractory acute and chronic GVHD. Recent Findings: Clinical trials in preventing GVHD demonstrate lower rates of severe acute GVHD and chronic GVHD with post-transplant cyclophosphamide. For acute GVHD, lower risk acute GVHD appears amenable to steroid-sparing therapies, such as sirolimus and itacitinib. Combinations with novel agents such as itolizumab appear promising for high risk acute GVHD. For steroid-refractory acute GVHD, ruxolitinib should be considered first line therapy. For chronic GVHD requiring therapy beyond steroids, ruxolitinib, belumosudil, and ibrutinib are now available and should be considered. Summary: Increasingly, GVHD has become a manageable complication after allogeneic HCT potentially translating to greater success with allogeneic HCT in the future. [ABSTRACT FROM AUTHOR]

Thymoma‐associated multiorgan autoimmunity (TAMA) presents with skin symptoms similar to those of graft‐versus‐host disease (GVHD), liver dysfunction, and enteritis, in the absence of a history of hematopoietic stem cell or bone marrow transplantation. TAMA is a type of paraneoplastic syndrome associated with thymoma. Its etiology is unclear but is thought to be a result of breakdown of immune tolerance. Histopathologically, TAMA is characterized by epidermal acanthosis with parakeratosis, individual cell keratinization, liquefaction degeneration, and intraepidermal infiltration of CD8‐positive lymphocytes. A 64‐year‐old female patient with a history of myasthenia gravis and thymoma treated with prednisolone (10 mg/day) and cyclosporine (150 mg/day) experienced erythema on her trunk after coronavirus disease 2019 (COVID‐19) onset. A psoriatic drug eruption was suspected and the possible causative drug was discontinued, but the skin rash failed to improve. A skin biopsy demonstrated GVHD‐like histopathological findings. Diarrhea, abdominal pain, and duodenal perforation occurred concurrently, leading to the diagnosis of TAMA. Thereafter, the patient continued prednisolone and cyclosporine in the same doses as the TAMA treatment and added topical steroids. During the disease course, candida fungemia and cytomegalovirus infection developed, resulting in the patient's death. The TAMA was considered to have been caused by the release of inflammatory cytokines, autoreactive T cell activation, and regulatory T cell dysfunction induced by COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Chronic graft‐versus‐host disease (cGVHD) is a leading cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). The sclerodermatous form of cGVHD can be particularly debilitating; however, orofacial sclerodermatous involvement remains poorly described. Objective: To characterize orofacial features of sclerodermatous cGVHD in a single center cohort of patients who underwent alloHCT. Study Design: Retrospective data were collected from electronic medical records and analyzed descriptively. Results: There were 39 patients who received alloHCT between 1993 and 2017 and developed orofacial sclerodermatous cGVHD. Concomitant cutaneous sclerodermatous cGVHD was common (n = 20, 51%). Orofacial sclerodermatous cGVHD features included fibrous bands of the buccal mucosa (n = 23, 59%), limited mouth opening (n = 19, 54%), perioral fibrosis (n = 8, 21%), and focal gingival recession (n = 4, 10%). Oral mucosal fibrosis was observed at the site of active or resolved chronic lichenoid inflammation in 30 patients, with all but two also presenting with a history of ulcerations. Management included jaw stretching exercises (n = 10; 6 stable/improved), surgery (n = 3; 2 improved), and intralesional corticosteroid injections (n = 2; 2 improved). Conclusions: Orofacial involvement with sclerodermatous cGVHD can present with multiple manifestations including fibrous banding, limited mouth opening, perioral fibrosis, and focal gingival recession. Surgical and non‐surgical management strategies may improve clinical function and reduce morbidity. [ABSTRACT FROM AUTHOR]

Background: We present the case of a patient who underwent hematopoietic progenitor cell transplantation from a fully compatible unrelated donor and subsequently developed Grade IV skin graft-versus-host disease (GVHD) resembling toxic epidermal necrolysis (TEN). Clinical case: An 11-year-old female, post-transplantation of hematopoietic progenitor cells from a 100% compatible unrelated donor, developed rash-like skin lesions on the trunk and extremities on day +35. A skin biopsy revealed dermal atrophy, vacuolization of the basal layer, and confluent apoptotic keratinocytes with mononuclear inflammatory cells in the dermoepidermis, confirming the diagnosis of TENlike acute cutaneous GVHD. Conclusion: The patient experienced an 80% remission of symptoms following dynamic management of immunosuppressants. [ABSTRACT FROM AUTHOR]

Simple Summary: Bronchitis obliterans syndrome (BOS) may occur following lung transplantation (LTx) or hematopoietic cell transplantation (HCT). The primary issue is graft-versus-host disease, complicating diagnosis. Treatment is based on empirical evidence and interdisciplinary knowledge. Recent advances emphasize understanding the etiology, clinical features, and pathobiology of BOS, fostering cross-disciplinary knowledge. Treatment algorithms are based on thorough research and expert clinical insights, with new therapies being explored to enhance survival rates and prevent LTx or re-transplantation. Background: Similar in histological characteristics and clinical manifestations, bronchiolitis obliterans syndrome (BOS) can develop following lung transplantation (LTx) or hematopoietic cell transplantation (HCT). In contrast to lung transplantation, where BOS is restricted to the lung allograft, HCT-related systemic graft-versus-host disease (GVHD) is the root cause of BOS. Because lung function declines following HCT, diagnosis becomes more difficult. Given the lack of proven effective medicines, treatment is based on empirical evidence. Methods: Cross-disciplinary learning is crucial, and novel therapies are under investigation to improve survival and avoid LTx. Recent advances have focused on updating the understanding of the etiology, clinical features, and pathobiology of BOS. It emphasizes the significance of learning from experts in other transplant modalities, promoting cross-disciplinary knowledge. Results: Our treatment algorithms are derived from extensive research and expert clinical input. It is important to ensure that immunosuppression is optimized and that any other conditions or contributing factors are addressed, if possible. Clear treatment algorithms are provided for each condition, drawing from the published literature and consensus clinical opinion. There are several novel therapies currently being investigated, such as aerosolized liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies, and B-cell-directed therapies. Conclusions: We urgently need innovative treatments that can greatly increase survival rates and eliminate the need for LTx or re-transplantation. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (alloSCT) is the cornerstone treatment for various hematopoietic disorders, but its utility is often compromised by chronic graft-versus-host disease (cGvHD), affecting skin integrity and leading to ulcer formations. Traditional treatments, including systemic and topical therapies, frequently fail in severe cases. This study retrospectively examines three patients with therapy-resistant ulcers due to cGvHD post-alloSCT treated at the University Hospital of Regensburg in 2023. We evaluated the therapeutic impact of human amniotic membrane (hAM) transplantation—a novel approach utilizing hAM's anti-inflammatory, anti-microbial, and anti-fibrotic properties for wound healing. Surgical debridement was followed by hAM application and routine follow-up. HAM transplantation led to complete wound closure in two out of three patients and a significant reduction in local pain and infection rates. The treatment alleviated the need for regular dressing changes within three months in two patients, demonstrating the hAM's efficacy in fostering rapid and sustained healing. The utilization of hAM represents a promising alternative for the management of refractory skin ulcers in cGvHD patients, particularly when conventional methods are inadequate. [ABSTRACT FROM AUTHOR]

The one-year survival rate for patients experiencing a relapse of B-cell acute lymphocytic leukemia (B-ALL) following hematopoietic stem cell transplantation (HSCT) is approximately 30%. Patients experiencing a relapse after allogeneic HSCT frequently encounter difficulties in obtaining autologous CAR-T products. We conducted a study involving 14 patients who received donor-derived CAR-T therapy for relapsed B-ALL following HSCT between August 2019 and May 2023 in our center. The results revealed a CR/CRi rate of 78.6% (11/14), a GVHD rate of 21.4% (3/14), and a 1-year overall survival (OS) rate of 56%. Decreased bone marrow donor cell chimerism in 9 patients recovered after CAR-T therapy. The main causes of death were disease progression and infection. Further analysis showed that GVHD (HR 7.224, 95% CI 1.42–36.82, P = 0.017) and platelet recovery at 30 days (HR 6.807, 95% CI 1.61–28.83, P = 0.009) are significantly associated with OS after CAR-T therapy. Based on the findings, we conclude that donor-derived CAR-T cells are effective in treating relapsed B-ALL patients following HSCT. Additionally, GVHD and poor platelet recovery impact OS, but further verification with a larger sample size is needed. [ABSTRACT FROM AUTHOR]

Introduction: Graft failure (GF) or poor graft function (PGF) remain critical obstacles in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), especially in recipients with HLA antibodies. Here, we performed a retrospective cohort study to investigate the efficacy and safety of the use of unrelated umbilical cord blood stem cells (UCBs) as a third-party adjuvant infusion in patients with HLA-antibodies undergoing haplo-HSCT. Methods: A total of 90 patients were divided into three groups: 17 patients in Group A (with positive HLA antibodies and who received UCB infusion), 36 patients in Group B (with positive HLA antibodies without UCB infusion), and 37 patients in Group C (without HLA antibody or UCB infusion). Results: The median age of patients included in Groups A, B, and C was 43 (IQR, 27 - 49.5), 33 (IQR, 20 - 48.75), and 30 (IQR, 18 - 46.5) years, respectively. All but one patient in Group B achieved granulocyte recovery within 28 days after transplantation. The median time to granulocyte engraftment were all 12 days for patients in Groups A, B, and C, respectively. All the patients in Group A achieved 100% donor chimerism without UCB engraftment. There were no significant differences in granulocyte or platelet engraftment time between the three groups. There were 1, 5, and 0 patients in Groups A, B, and C, respectively, who developed PGF. The cumulative incidence rates for any grade of acute graftversus-host disease (aGVHD) were comparable among the three groups. Patients in Group B presented a greater incidence of cGVHD than did those in Group A (P = 0.002) and Group C (P = 0.006). Patients in Group A presented more limited and milder cGVHD than those in Group C (P < 0.0001). The 1-year relapse-free survival (RFS) was 70.6% (95% CI, 0.47 - 0.87), 55.6% (95% CI, 0.40 - 0.70), and 77.9% (95% CI, 0.63 - 0.89) in Groups A, B, and C, respectively. Discussion: Our results indicated that patients who were positive for HLA antibodies were at a greater risk of developing GF/PGF. Co-infusion with UCBs was safe and improved engraftment, cGVHD, and improved the 1-year RFS to some extent. [ABSTRACT FROM AUTHOR]

Abstract Systemic administration of Janus kinase (JAK) inhibitors is effective in treating chronic graft-versus-host disease (cGVHD) but is associated with side effects. Topical drug administration effectively minimizes side effects. We aimed to investigate potential trends of the efficacy of topical delgocitinib administration in a mouse model. Allogenic bone-marrow transplantation (BMT) was performed from B10.D2. to BALB/c mice, leading to sclerodermatous GVHD. GVHD mice were treated with delgocitinib eye drops or ointment with samples analyzed at 4 weeks post-BMT. Topical delgocitinib ointment and eye-drop administration significantly increased the meibomian gland (MG) area and attenuated corneal epithelial damage. Pathological and immunohistochemical analyses revealed a substantial reduction in inflammation and pathological fibrosis of the skin and eyelids in delgocitinib-treated GVHD mice. Signal transducer and activator of transcription (STAT)1, STAT3, and STAT5A phosphorylation was significantly increased in the back skin and eyelids of vehicle-treated GVHD mice; topical delgocitinib administration significantly reduced the expression of these phosphorylated STAT molecules. Delgocitinib eye drops significantly attenuated corneal epithelial damage, MG acinar depletion, and inflammatory cells infiltration in GVHD mouse corneas. The JAK/STAT signaling pathway was significantly upregulated in GVHD mice. In summary, our data suggested that topical delgocitinib administration had the potential to attenuate cGVHD phenotype severity in the skin and eyes of sclerodermatous GVHD mice.

Abstract Hematopoietic stem cell transplantation (HSCT) is a highly effective therapy for malignant blood illnesses that pose a high risk, as well as diseases that are at risk due to other variables, such as genetics. However, the prevalence of graft-versus-host disease (GVHD) has impeded its widespread use. Ensuring the stability of microbial varieties and associated metabolites is crucial for supporting metabolic processes, preventing pathogen intrusion, and modulating the immune system. Consequently, it significantly affects the overall well-being and susceptibility of the host to disease. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may experience a disruption in the balance between the immune system and gut bacteria when treated with medicines and foreign cells. This can lead to secondary intestinal inflammation and GVHD. Thus, GM is both a reliable indicator of post-transplant mortality and a means of enhancing GVHD prevention and treatment after allo-HSCT. This can be achieved through various strategies, including nutritional support, probiotics, selective use of antibiotics, and fecal microbiota transplantation (FMT) to target gut microbes. This review examines research advancements and the practical use of intestinal bacteria in GVHD following allo-HSCT. These findings may offer novel insights into the prevention and treatment of GVHD after allo-HSCT.

Abstract Treatment of advanced cutaneous T‐cell lymphoma (CTCL) can be challenging. To date, the only potentially curative treatment option for advanced CTCL is allogeneic hematopoietic stem cell transplantation. We report on a patient with mycosis fungoides who received allogeneic hematopoietic stem cell transplantation due to rapid progression of the disease. Eight months after transplantation, relapse as well as chronic graft‐versus‐host disease occurred. Therefore, we initiated different treatment modalities, including bexarotene, extracorporeal photopheresis, topical treatment as well as the Janus‐kinase‐inhibitor Ruxolitinib. Even though the patient experienced high morbidity due to the allogeneic hematopoietic stem cell transplantation, 3 years after he is still alive and reports good health‐related quality of life. With this case, we aim to demonstrate that the posttransplant course can be difficult, balancing between relapse and graft‐versus‐host disease. Nevertheless, patients can benefit in terms of survival and their health‐related quality of life. Therefore, allogeneic hematopoietic stem cell transplantation should be considered as a treatment option, especially for patients with advanced CTCL and poor prognosis.

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, drug-induced adverse reaction characterized by skin eruptions, lymphadenopathy, fever, and a broad range of other bodily manifestations. The spectrum of histopathologic and clinical presentations is wide; therefore, DRESS syndrome can mimic other diseases. Case Presentation: We present a case of a 4-year-old male patient who started chemotherapy with vincristine, cytarabine, and etoposide. The first clinical signs were fever, hemodynamic in-stability, and maculopapular erythema. Biopsies of skin lesions were taken, and hyperkeratosis, focal parakeratosis, acanthosis with slight spongiosis, and intraepithelial dyskeratotic cells were observed. There was a perivascular lymphoid infiltrate with abundant eosinophils in the dermis, and eosinophil permeations to the acrosyringium and epithelium were found. Conclusion: DRESS syndrome is a drug-induced reaction that shares histopathological findings in skin biopsies with those seen in graft-versus-host disease. Although the histological findings are non-pathognomonic, they were characteristic enough to be of importance in the differential diagnosis.

Muhammad B Qureshi,1 Jose O Garcia,1 Jaxon Quillen,2 Carolyn Mead-Harvey,2 Christina Wentz,3 Cherie B Nau,4 Muriel Schornack,4 Keith Baratz,4 Sanjay V Patel,4 Joanne Shen5 1Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA; 2Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA; 3Illinois College of Optometry, Chicago, IL, USA; 4Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA; 5Department of Ophthalmology, Mayo Clinic, Scottsdale, AZ, USACorrespondence: Joanne Shen, Department of Ophthalmology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, USA, 85259, Tel +1 480-301-8085, Fax +1 480-301-7326, Email shen.joanne@mayo.eduPurpose: To compare baseline characteristics and treatment of chronic ocular graft-versus-host disease (oGVHD) patients in two treatment locations.Patients and Methods: Patients diagnosed with definite chronic oGVHD between September 1, 2014 and September 20, 2021 at two locations were identified. IRB-approved retrospective chart review was conducted for the following data: demographic information, ocular surface disease index (OSDI), corneal fluorescein staining (CFS), and treatment(s) used. Differences by site were assessed using Pearson’s Chi-Square tests and two-sample t-tests; differences by time were assessed using paired t-tests.Results: At baseline, Clinic 1 (C1) patients had a worse mean OSDI score (47.8 vs 36.3, p = 0.011) and CFS in both OD (1.3 vs 0.8, p = 0.005) and OS (1.3 vs 0.6, p < 0.001) compared to Clinic 2 (C2). Comparing baseline to endpoint, C1 patients experienced an improvement in OSDI (− 17.26, p < 0.001), CFS OD (− 0.50, p < 0.001), and CFS OS (− 0.51, p < 0.001) at C1. Change in OSDI, CFS OD, or CFS OS was not statistically significant at C2. Despite similar follow-up length, C1 demonstrated more clinic visits (10.4 vs 3.4, p < 0.001) and more treatment trials (4.9 vs 2.4, p < 0.001) compared to C2. Punctal plugs (85.5% vs 61.2%, p = 0.002), punctal cautery (69.7% vs 28.6%, p < 0.001), topical steroids (72.4% vs 22.4%, p < 0.001), and autologous serum tears (AST) (52.6% vs 8.2%, p < 0.001) were used more frequently at C1 than at C2.Conclusion: oGVHD patients at C1 experienced significant improvement in OSDI and corneal fluorescein staining and compared to patients at C2, had more frequent follow-up and use of punctal plugs, punctal cautery, topical steroids, and AST.Keywords: graft-versus-host disease, GVHD, chronic GVHD, dry eye disease, ocular GVHD, keratoconjunctivitis sicca, KCS

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD.

Summary Allogeneic haematopoietic stem cell transplantation (allo‐HSCT) is an effective therapy for acute myeloid leukaemia (AML), predominantly due to its potent graft‐versus‐leukaemia (GVL) effect. However, leukaemia relapse remains a major obstacle to the success of allo‐HSCT. In this study, we demonstrated that gallic acid (GA), a natural dietary compound, can enhance T‐cell‐mediated GVL effects both in vitro and in vivo. GA‐treated T cells exhibited increased activation and elevated secretion of cytotoxic cytokines, leading to the apoptosis of AML cells in co‐culture systems in vitro. In a non‐irradiated leukaemia mouse model, we showed that GA treatment prolonged the survival of leukaemic mice and reduced leukaemia cell infiltration. Further analysis revealed that GA treatment increased T‐cell activation and tumour necrosis factor‐α secretion. Moreover, integrated transcriptomic and proteomic analyses indicated that GA augments T‐cell‐mediated GVL effects through the activation of the MAPK and NF‐κB pathways. Blocking these pathways individually diminished the protective effect of GA in AML model mice. Importantly, GA administration did not accelerate graft‐versus‐host disease (GVHD) progression in a mouse model. In conclusion, our study revealed that GA can enhance the GVL effects of T cells without exacerbating GVHD, offering insights into its potential to improve outcomes for patients after HSCT. [ABSTRACT FROM AUTHOR]

Summary This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo‐HCT) platforms in patients with adult T‐cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)‐haploidentical‐related donors using post‐transplant cyclophosphamide (PTCY), HLA‐matched related donors (MRD), HLA‐matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo‐HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non‐relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow‐up of 794 days for survivors, 2‐year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2‐year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft‐versus‐host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo‐HCT with PTCY is a safe and effective platform for patients with adult T‐cell leukaemia/lymphoma. [ABSTRACT FROM AUTHOR]

Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. Measurements and Main Results: In total, 1,164 patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented with multiple organ dysfunction, including acute respiratory failure in 40% (n = 461). The median sepsis-related organ failure assessment score was 6 (interquartile range, 4–8). Invasive mechanical ventilation, renal replacement therapy, and vasopressors were required in 438 (38%), 221 (19%), and 468 (41%) patients, respectively. ICU mortality was 26% (302 deaths). Ninety-day, 1-year, and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age > 56 years (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.53–2.60]; P < 0.001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR, 1.68 [95% CI, 1.17–2.40]; P = 0.005), corticosteroid-refractory acute graft-versus-host disease (OR, 1.63 [95% CI, 1.38–1.93]; P < 0.001), need for vasopressors (OR, 1.9 [95% CI, 1.42–2.55]; P < 0.001), and mechanical ventilation (OR, 3.1 [95% CI, 2.29–4.18]; P < 0.001) were independently associated with 90-day mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality. [ABSTRACT FROM AUTHOR]

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening, drug-induced adverse reaction characterized by skin eruptions, lymphadenopathy, fever, and a broad range of other bodily manifestations. The spectrum of histopathologic and clinical presentations is wide; therefore, DRESS syndrome can mimic other diseases. Case Presentation: We present a case of a 4-year-old male patient who started chemotherapy with vincristine, cytarabine, and etoposide. The first clinical signs were fever, hemodynamic in-stability, and maculopapular erythema. Biopsies of skin lesions were taken, and hyperkeratosis, focal parakeratosis, acanthosis with slight spongiosis, and intraepithelial dyskeratotic cells were observed. There was a perivascular lymphoid infiltrate with abundant eosinophils in the dermis, and eosinophil permeations to the acrosyringium and epithelium were found. Conclusion: DRESS syndrome is a drug-induced reaction that shares histopathological findings in skin biopsies with those seen in graft-versus-host disease. Although the histological findings are non-pathognomonic, they were characteristic enough to be of importance in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Certain immune cells, including neutrophils, macrophages, dendritic cells, B cells, Breg cells, CD4+ T cells, CD8+ T cells, and Treg cells, establish enduring residency within the bone marrow. Their distinctive interactions with hematopoiesis and the bone marrow microenvironment are becoming increasingly recognized alongside their multifaceted immune functions. These cells play a dual role in shaping hematopoiesis. They directly influence the quiescence, self-renewal, and multi-lineage differentiation of hematopoietic stem and progenitor cells through either direct cell-to-cell interactions or the secretion of various factors known for their immunological functions. Additionally, they actively engage with the cellular constituents of the bone marrow niche, particularly mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts, to promote their survival and contribute to tissue repair, thereby fostering a supportive environment for hematopoietic stem and progenitor cells. Importantly, these bone marrow immune cells function synergistically, both locally and functionally, rather than in isolation. In summary, immune cells residing in the bone marrow are pivotal components of a sophisticated network of regulating hematopoiesis. [ABSTRACT FROM AUTHOR]

This study assessed the effect of serum magnesium levels and their role in the outcome of allogeneic hematopoietic cell transplantation (allo-HSCT) in acute leukemia. Fifty-four patients with acute leukemia who underwent allo-HSCT were divided into two groups according to their serum magnesium levels before transplantation. The results showed that serum magnesium level is an independent factor influencing the prognosis of patients undergoing allo-HSCT. Low magnesium levels were associated with inferior overall survival and event-free survival compared with the associations of high magnesium levels (HR = 0.149; (95% CI: 0.029-0.755 for overall survival; HR = 0.369; 95% CI: 0.144-0.949, p = 0.039 for event-free survival). The competing risk model showed that the cumulative incidence of acute graft-versus-host disease was significantly low in the high magnesium group (p = 0.028). In general, there is a correlation between high magnesium levels and superior outcomes, including less and milder acute graft-versus-host disease, which does not affect cyclosporine-A levels. These findings provide valuable information for identifying the risk of poor prognosis in patients preparing for transplantation. [ABSTRACT FROM AUTHOR]

Background: Interleukin-17 (IL-17) is elevated in human inflammatory and autoimmune diseases. The polymorphism in the promoter region of the IL-17 A gene is associated with susceptibility to several inflammatory diseases, including acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation from adult donors. However, the impacts of IL-17 A polymorphism on cord blood transplantation (CBT) outcomes remain unclear. Objective: The objective of this study was to assess the impact of IL-17 A polymorphism rs2275913 on GVHD, survival, relapse, non-relapse mortality (NRM), and hematopoietic recovery after CBT. Study Design: We conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from January 2005 to March 2023 for whose recipient or donor DNA samples were available. IL-17 A genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2275913. Results: A total of 158 recipients and 136 donors were evaluated in this study. Multivariate analysis showed that rs2275913 GA or AA recipients were associated with Increased risk of grades II to IV acute GVHD compared to GG recipients (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00-2.13; P = 0.047). Serum IL-17 A levels at eight weeks were significantly higher in rs2275913 GA or AA recipients compared to GG. The rs2275913 polymorphism did not affect survival, relapse, NRM, or hematopoietic recovery after single-unit CBT. Conclusion: Our data showed recipient IL-17 A polymorphism rs2275913 was associated with the risk of grade II to IV acute GVHD in adults undergoing single-unit CBT. However, the rs2275913 polymorphism in recipients and donors did not affect survival or relapse. Thus, the polymorphism of IL-17 A rs2275913 in recipients might predict the risk of acute GVHD after single-unit CBT. [ABSTRACT FROM AUTHOR]

Background and Objectives: Graft-versus-host disease (GvHD) frequently complicates hematopoietic stem cell transplantation (HSCT). Emerging evidence suggests a correlation between gut microbiota and GvHD risk. This study aims to elucidate the microbiota profiles in HSCT patients before and after transplantation and their association with GvHD. Materials and Methods: This study, conducted from December 2022 to December 2023, involved the collection of 15 stool samples from HSCT patients. Bacterial content was quantified using real-time PCR, while interleukin-6 levels were assessed via ELISA. Results: Among the 15 participants (8 male, 7 female), 9 underwent allogeneic HSCT (allo-HSCT) and 6 received autologous HSCT. In the aGvHD group, there was a significant reduction in the abundance of Bacteroides and Bifidobacterium compared to those without aGvHD. Additionally, declines were observed in Clostridium and Firmicutes populations. The genus Blautia also showed reduced prevalence in the aGvHD group, whereas no significant differences were noted in the uncomplicated group. ELISA analysis revealed that interleukin-6 levels remained within the normal range (30-960 pg/ml) with no significant elevation in the aGvHD group. Conclusion: The study highlights a notable association between alterations in gut microbiota, specifically reductions in certain bacterial populations and the development of aGvHD following allo-HSCT. [ABSTRACT FROM AUTHOR]

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient's tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD. [ABSTRACT FROM AUTHOR]

Purpose: To figure out the roles of tear inflammatory cytokines in Ocular graft-versus-host disease (oGVHD) symptoms by analyzing tear cytokine levels and related factors. Methods: This prospective study involved 27 post-HSCT patients and 19 controls with dry eye disease. Analyses included tear cytokine (IL-6, IL-10, and TNF-α), ocular surface evaluation, and conjunctival impression cell examination. Tear cytokine levels were evaluated in three grades of corneal epithelial lesions. The study also analyzed the correlation between tear cytokine levels and ocular surface parameters. Tear cytokine levels were then used in a Receiver Operating Characteristic (ROC) curve and linear regression model to predict oGVHD related factors. Results: IL-6 has good diagnostic efficacy in oGVHD related dry eye. Elevated levels of tear IL-6 and TNF-α were observed in the group with severe corneal epithelial lesions. IL-6 levels were positively correlated with corneal fluorescein staining (CFS), eyelid margin hyperemia, conjunctival lesions, and meibum secretion. IL-6 showed excellent predictive ability with Area Under the Curve (AUC) values all greater than 0.70 (p < 0.05). IL-10 and TNF-α were negatively correlated with the meibomian gland proportion and conjunctival goblet cell (GC) density, while TNF-α was positively correlated with CFS and eyelid margin hyperemia. Conclusion: Dry eye symptoms related to ocular GVHD, can be partly diagnosed and assessed using various tear cytokine level detection methods. [ABSTRACT FROM AUTHOR]

Purpose: Despite the importance of adherence to immunosuppressants (IMMs) after an allogeneic haematopoietic stem cell transplant (HSCT) for the treatment of acute graft-versus-host disease (aGvHD), no studies to date have reported the experiences of such patients concerning medication adherence (MA). Therefore, the aim of the study was to explore the perspective on MA to immunosuppressive oral therapy among allogeneic HSCT patients with aGvHD. Methods: A qualitative descriptive study following a reflexive thematic analysis methodological approach was performed involving a purposive sample of 16 patients with aGvHD who were being cared for in the outpatient setting of a bone marrow transplant centre and were willing to participate. Semi-structured audio-recorded interviews were conducted, transcribed verbatim and thematically analysed; member checking was performed. COnsolidated criteria for REporting Qualitative research (COREQ) and the ESPACOMP Medication Adherence Reporting Guideline were followed. Results: Participants aged 25–74 years and mostly males (62.5%) were recruited for this study; 56.2% developed grade I, 37.5% grade II and 6.3% grade III aGvHD; 56.2% were receiving treatment with both cyclosporine and prednisone. Patients' perspectives have been summarised into four themes, named: “Transiting from an external obligation to a habit”; “Being in the middle between the negative and positive effects of the IMMs”; “Failure to systematically respect the rules”; and “Adopting personal strategies to become adherent”. After difficulties with the perception of feeling obliged, patients became used to adhering to IMMs. Although there were failures in systematically taking the medication correctly and there were episodes of non-adherence, the adoption of personal strategies helped patients to become adherent to their medication schedules. Conclusions: MA in patients with aGvHD is a complex behaviour and is often a challenge. These results can help healthcare professionals and centres to understand how best to design tailored strategies and behavioural interventions to maximise patients’ MA to IMMs. [ABSTRACT FROM AUTHOR]

Aims/Background Although the incidence of nephrotic syndrome (NS) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively low, it can significantly affect patients' quality of life and may even be life-threatening. Therefore, it is essential to investigate the clinical manifestations and prognosis of patients with NS after allo-HSCT, as well as to identify potential high-risk factors associated with this condition. Methods We investigated the incidence rate of NS in 1457 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital, Zhejiang University School of Medicine between June 2007 and March 2020. Among these, we identified 12 patients who developed NS after allo-HSCT (NS group). For comparison, we selected a control group of 48 patients matched by gender and transplantation time who did not develop NS. Univariate and multivariate logistic regression analyses were performed using SPSS software, version 25.0 (IBM Corp., Armonk, NY, USA) to identify independent risk factors for NS. Results Among the 1457 patients, 12 (0.82%) developed post-transplantation NS, with a median onset time of 14.99 months (range: 5.39–48.43 months) after transplantation. Univariate analysis indicated that the occurrence of post-transplantation NS was significantly correlated with total cholesterol (TC) levels at 6 months post-transplantation (p = 0.041), triglycerides (TG) and TC levels at 1 year post-transplantation (p = 0.004 and p = 0.011, respectively), and cytomegalovirus (CMV) infection (p = 0.002). Multivariate analysis revealed that CMV infection (p = 0.004, odds ratio = 15.871; 95% confidence interval: 2.465–102.194) was independently associated with the development of NS. Conclusion After allo-HSCT, NS may manifest as a form of chronic graft-versus-host disease. CMV infection is a risk factor for developing NS. Effective management through the administration of calcium inhibitors and corticosteroids can enable long-term survival in these patients. [ABSTRACT FROM AUTHOR]

Background Monoclonal antibodies (mAbs) are utilized broadly to treat cancer and infectious diseases, and mAb exposure (serum concentration over time) is one predictor of overall treatment efficacy. Herein, we present findings from a clinical trial evaluating the pharmacokinetics of the long-acting mAb sotrovimab targeting severe acute respiratory syndrome coronavirus 2 in hematopoietic cell transplant (HCT) recipients. Methods All participants received an intravenous infusion of sotrovimab within 1 week prior to initiating the pretransplant preparative regimen. The serum concentration of sotrovimab was measured longitudinally for up to 24 weeks posttransplant. Results Compared to non-HCT participants, we found that mAb clearance was 10% and 26% higher in autologous and allogeneic HCT recipients, respectively. Overall sotrovimab exposure was approximately 15% lower in HCT recipients compared to non-HCT recipients. Exposure was significantly reduced in HCT recipients who developed diarrhea and lower gastrointestinal graft-versus-host disease (GVHD) posttransplant. Conclusions These data show that sotrovimab exposure may be reduced in HCT recipients, possibly related to increased gastrointestinal clearance in patients with GVHD. This phenomenon has implications for dose selection and duration of efficacy with sotrovimab and potentially other mAbs in this vulnerable patient population. Thus, mAb dose regimens developed in non-HCT populations may have to be optimized when applied to HCT populations. [ABSTRACT FROM AUTHOR]

Background: The optimal choice for graft‐versus‐host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo‐SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti‐thymocyte globulin (ATG) are two common strategies, but little is known about their combination. Methods: Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo‐SCT in complete remission between 2007 and 2021 at 260 EBMT‐participating centers who received either PTCy (n = 2999), ATG (n = 358), or combination prophylaxis (n = 292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow‐up was 31.8 months. Results: On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female‐to‐male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p =.003), worse leukemia‐free survival (HR, 1.4; p =.002), overall survival (HR, 1.49; p =.0009), and GVHD‐free and relapse‐free survival (HR, 1.29; p =.012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2–4 (HR, 0.51; p =.0003) and grade 3–4 (HR, 0.5; p =.018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. Conclusion: The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo‐SCT for AML. This study analyzed 3649 adult acute myeloid leukemia (AML) patients undergoing haploidentical stem cell transplantation (haplo‐SCT) with either posttransplant cyclophosphamide (PTCy), anti‐thymocyte globulin (ATG), or their combination, and showed that ATG alone had worse outcomes compared to PTCy, but combining PTCy and ATG significantly reduced acute graft‐vs‐host disease (GVHD) rates without affecting transplant outcomes. This suggests the PTCy and ATG combination could be a superior GVHD prophylaxis strategy in haplo‐SCT for AML. [ABSTRACT FROM AUTHOR]

Drug‐induced liver injury (DILI) presents unique challenges in clinical practice. While some types of DILI are mild and resolve quickly after removing the drug, other situations are more complex, with competing aetiologies or underlying liver disease. Guidelines from professional societies agree that the liver biopsy retains a role in understanding and managing DILI in certain situations. Liver biopsy allows characterization of the histological pattern of injury as well as assessment of severity. Inflammatory infiltrates, bile duct injury or loss and vascular injury are all revealed by liver biopsy. Communication between the hepatopathologist and clinical team with clinicopathological correlation of the findings is necessary for the best determination of causality and differentiation from other diseases of exclusion, like autoimmune hepatitis and graft‐versus‐host disease. This review highlights important aspects of the role of liver biopsy in DILI evaluation. [ABSTRACT FROM AUTHOR]

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD. [ABSTRACT FROM AUTHOR]

Background: Cutaneous graft‐versus‐host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation. Phototherapy has been used to treat cutaneous GVHD, but data on its safety and efficacy are sparse. Aim: Review the current medical literature regarding the efficacy, dosing, and safety of various types of phototherapies for the treatment of cutaneous GVHD. Methods: A systematic review of PubMed, Embase, Cochrane, and ClinicalTrials databases was performed. Publications were screened according to the PRISMA guidelines. Exclusion criteria comprised case reports and case series reporting less than five patients, review articles, and articles not published in English. Results: A total of 28/1304 (2.5%) studies were included. Fifteen studies (n = 267 patients) focused on psoralen and ultraviolet (UV) A (PUVA), in which 65.5% of patients received concomitantly other systemic treatments. The response rate was 89.9%, with a mean of 33.2 treatments. Adverse events were recorded in 54% but were mainly mild. Eight studies, encompassing 95 patients, focused on narrow‐band (NB) UVB. A response was observed in 94%, with a mean number of 26 treatments and 8.6% adverse effects. UVA1 was reported in six studies (n = 132 patients). A response was recorded in 89.3% with a mean of 26.2 treatments. Adverse events were noted in 70.1%, with a discontinuation rate of 10.9%. It should be noted that adverse events were recorded during the follow‐up period of the studies, which varied significantly, ranging from no follow‐up to 31 months. Conclusions: Current data regarding the use of phototherapy for the treatment of cutaneous GVHD are based on retrospective studies and case series. The present report advocates the use of one of the three modalities of phototherapy as an effective and safe adjunctive treatment for cutaneous GVHD, especially NB UVB phototherapy. [ABSTRACT FROM AUTHOR]

Aims: To study the effects of routine HLA screening and the policy of avoiding donor‐dominant one‐way HLA match to prevent graft‐versus‐host disease (GVHD) after living donor liver transplantation (LDLT). Patients and Methods: The records of potential living liver donors and recipients who attended our center between 2007 and 2018 were reviewed retrospectively. Results: Of the 149 patients who underwent LDLT and survived longer than 3 months, two developed GVHD despite our strict policy. The first patient presented with grade II GVHD limited to the skin. She was treated successfully by briefly discontinuing immunosuppression and switching to everolimus. In the second case, the policy had been relaxed due to the availability of a single donor for ABO‐incompatible transplantation without any intervention to decrease anti‐A antibody levels (special case: A2 to O). Nevertheless, the patient presented with grade I GVHD limited to skin and was treated successfully by adding oral methylprednisolone to tacrolimus and mycophenolate mofetil. To the best of our information, this is the second reported case who recovered from GVHD after LDLT from a donor, homozygous at HLA A, B and DR and a recipient, heterozygous for all. Sixteen potential donors (1.2% of all candidates) of 14 recipients were disqualified solely on the basis of the HLA results; five of these patients died due to unavailability of another donor. Conclusion: The results support the policy of avoiding HLA combinations that preclude immune recognition of graft lymphocytes as foreign to decrease the risk of GVHD after LDLT. [ABSTRACT FROM AUTHOR]