[Pathogenesis and novel therapies for chronic GVHD].

Treatment for chronic graft-versus-host disease, the most important long-term complication of allogeneic hematopoietic cell transplantation, has changed significantly over the past decade. Development of novel targeted therapies has advanced as objective criteria for the diagnosis and evaluation of chronic GVHD have been established and understanding of the biological pathways to pathogenesis has increased. This paradigm shift is driving chronic GVHD practice significantly toward individualized therapy while minimizing exposure to steroids. Treatment using a variety of novel agents, tailored to each individual patient's condition, is expected to improve quality of life and overall survival by preventing chronic GVHD, controlling disease progression, and maintaining motor and occupational functions. This article reviews the pathogenesis of chronic GVHD and discusses prospects for the treatment of chronic GVHD, along with recently approved drugs and promising drugs in development.

Chronic Ocular GVHD Treatment at Two Locations of a Tertiary Referral Center.

Purpose: 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.

Oral Chronic Graft-versus-Host Disease and Oral Health after Allogeneic Hematopoietic Cell Transplantation - What the Care Team Needs to Know.

Oral chronic graft-versus-host disease (cGVHD) can present with a multitude of clinical signs and is associated with morbidity and lower quality of life. Oral cGVHC may affect the oral mucosa (reticular white striae, erythema, and/or ulcerations), the salivary glands (hyposalivation and/or xerostomia) and the peri-oral soft tissues (fibrosis and trismus). This review provides a practical and concise approach to the diagnosis and management of oral health needs in pediatric and adult alloHCT recipients within the first 2 years post-transplantation.

Improving Outcomes in Allogeneic Transplantation and Chronic Graft-versus-Host Disease Patients through Lifestyle Medicine: Current Landscape and Future Directions.

Although lifestyle interventions have shown promise in oncology and for cancer survivorship, their potential to improve outcomes in allogeneic hematopoietic cell transplantation (allo-HCT) and chronic graft-versus-host disease (cGVHD) patients remains to be fully explored. Given the high rates of cardiovascular disease, metabolic syndrome, and secondary malignancy in this patient population, lifestyle modifications can serve as a vital frontline defense against chronic diseases. Current research has illuminated the potential supportive role of lifestyle interventions in the solid cancer patient population, which is encouraging future lifestyle medicine research for patients with hematologic malignancies and allo-HCT recipients. Recent studies have indicated the pernicious effects of poor lifestyle choices on the course of cGVHD development and survival. The intersection between certain pillars of lifestyle medicine (ie, nutrition and exercise) and allo-HCT patient outcomes has been more well documented than that of other pillars (ie, social relationships and spirituality). Ongoing randomized trials studying the effects of exercise and nutrition on clinical outcomes in cGVHD and allo-HCT patients may provide important future evidence of the role of lifestyle medicine in this patient population. In this review, we describe the current landscape of lifestyle medicine in allo-HCT and cGVHD, its potential, and propose ways to further develop this evolving field of medicine.

Infectious Disease Considerations in Chronic Graft-versus-Host Disease and Transplantation Survivors.

Chronic graft-versus-host disease is a frequent and serious complication of allogeneic hematopoietic cell transplantation and is associated with an increased risk of serious infections. Impaired humoral immunity increases the risk of recurrent or severe sinopulmonary infections, and functional asplenia predisposes to infections from encapsulated organisms. Herpesvirus infections and community-acquired respiratory viral infections are problematic as well. Pneumocystis pneumonia remains a risk, and mold infections occur in some patients. Understanding the epidemiology and pathophysiology of these infections is important for determining optimal monitoring and prophylaxis, and guiding patient counseling.

Soluble MICA concentrations and genetic variability of MICA and its NKG2D receptor as factors affecting Graft-versus-Host Disease development after allogeneic haematopoietic stem cell transplantation.

Despite new treatment strategies, graft-versus-host disease (GvHD) remains a formidable complication after allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the impact of polymorphisms and expression of MICA and NKG2D receptor on the development of GvHD in allogeneic HSCT recipients. Soluble MICA (sMICA) concentration was measured in serum collected 30 days after transplantation and the genetic variability of MICA and NKG2D genes was evaluated. The frequency of NKG2D+NK cells was determined by flow cytometry before and (21, 30, 60 and 90 days) after transplantation. Recipients with acute GvHD grades II-IV carried the NKG2D rs1049174 C allele more frequently than controls or patients with no or mild disease. Patients with chronic GvHD had higher frequency of NKG2D expressing NK cells posttransplant, reflecting increased activity of their NK cells. Although no direct relationship between MICA SNPs and GvHD were observed, the presence of MICA rs1051792 GG genotype correlated with elevated sMICA levels and increased serum level of sMICA was associated with higher risk of chronic GvHD. Our findings suggest that sMICA concentration may serve as a potential biomarker for chronic GvHD and emphasize the impact of genetic variability of NKG2D and its surface expression on the HSCT outcome.

Akkermansia in the gastrointestinal tract as a modifier of human health.

Akkermansia sp are common members of the human gut microbiota. Multiple reports have emerged linking the abundance of A. muciniphila to health benefits and disease risk in humans and animals. This review highlights findings linking Akkermansia species in the gastrointestinal (GI) tract to health outcomes across a spectrum of disorders, encompassing those that affect the digestive, respiratory, urinary, and central nervous systems. The mechanism through which Akkermansia exerts a beneficial versus a detrimental effect on health is likely dependent on the genetic makeup of the host metabolic capacity and immunomodulatory properties of the strain, the competition or cooperation with other members of the host microbiota, as well as synergy with co-administered therapies.

Platelet Pathogen Reduction Technology-Should We Stay or Should We Go ?

The recent COVID-19 pandemic has significantly challenged blood transfusion services (BTS) for providing blood products and for keeping blood supplies available. The possibility that a similar pandemic event may occur again has induced researchers and transfusionists to investigate the adoption of new tools to prevent and reduce these risks. Similarly, increased donor travelling and globalization, with consequent donor deferral and donor pool reduction, have contributed to raising awareness on this topic. Although recent studies have validated the use of pathogen reduction technology (PRT) for the control of transfusion-transmitted infections (TTI) this method is not a standard of care despite increasing adoption. We present a critical commentary on the role of PRT for platelets and on associated problems for blood transfusion services (BTS). The balance of the cost effectiveness of adopting PRT is also discussed.

Haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for Fanconi anemia with/without anti-thymocyte globulin.

Background: We present comparative data of children with Fanconi anemia undergoing haploidentical hematopoietic stem cell transplantation (HSCT) with or without the addition of rabbit anti-thymocyte globulin (r-ATG) to the conditioning regimen. Patients and methods: This retrospective study included children with Fanconi anemia aged up to 18 years who underwent haploidentical HSCT between January 2015 and December 2022. The children were included in two cohorts in this study. Cohort 1 included children who received conditioning with fludarabine/cyclophosphamide/single fraction of 2 Gy TBI. The children in cohort 2 received the same conditioning along with r-ATG. Post-transplant cyclophosphamide was administered at a dose of 25 mg/kg on day3 and day4 in both cohorts. Results: A total of 35 children were included in the study, 25 in cohort 1 and 10 in cohort 2. Neutrophil engraftment was documented around day 14-16 post infusion in 21 children (84%) in cohort 1 and in 8 children (80%) in cohort 2. There was a significant difference in the incidence of the severity of graft versus host disease (GVHD) between the two cohorts (p = 0.003). In cohort 1, acute GVHD was documented in 17 children (68%), with grade 1/2 skin GVHD in 10 children, and grade 3/4 skin and gut GVHD in 7 children. Grade 4 gut GVHD was the cause of death in three children in cohort 1. In cohort 2, acute GVHD was documented in one child (10%) who had grade 4 skin and gut GVHD and succumbed to the above. Chronic GVHD was noted in nine (36%) children in cohort 1, and in one child (10%) in cohort 2. Cytomegalovirus reactivation was documented in 11 children (44%) in cohort 1 and three children (30%) in cohort 2. Overall survival was found to be 16/25 (64%) in cohort 1, with a median follow-up of 49 months, and 7/10 (70%) in cohort 2, with a median follow-up of 12 months. Conclusion: Serotherapy with r-ATG significantly reduced the incidence of GVHD from 68% to 10% in children with Fanconi anemia, with an increase in overall survival from 64% to 70%, although it did not affect graft failure. Further studies should focus on decreasing graft failure rates with early HSCT before multiple transfusions.

Non-invasive Estimation of Microvasculopathy & Endothelial Dysfunction in Stem Cell Transplant Recipients and its Relationship with GVHD.

Introduction: Microvasculopathy and endothelial dysfunction play important roles in the development of post-transplant complications, including graft-versus-host disease (GVHD). We assessed structural microvasculopathy by employing nailfold video capillaroscopy (NFVC) and endothelial dysfunction via flow-mediated dilatation (FMD) of the brachial artery in recipients of hematopoietic stem cell transplantation. Patients and methods: Recipients of stem cell transplantation were included in this study post day+100 and divided into two cohorts. The first cohort consisted of 35 recipients of allogeneic hematopoietic stem cell transplantation (HCT) and the second cohort was comprised of 31 recipients of autologous HCT. A third cohort included 35 healthy individuals. NFVC was conducted on the second to fifth fingers of both hands using an Optilia video capillaroscope at 200× magnification, and the images were analyzed according to the European Alliance of Associations for Rheumatology (EULAR) criteria. The following parameters were used to measure vasculopathy: (a) median capillary density, derived from the capillary density of eight fingers, (b) median capillary diameter, derived from maximum capillary apical diameters of eight fingers, and (c) significant neoangiogenesis (neoangiogenesis present in ≥2 fingers). FMD of the right brachial artery was observed by high-resolution ultrasonography using the principle of post-occlusive reactive hyperemia, and video images were analyzed using edge-detecting software. Results: The median capillary diameter was significantly higher in the allo-HCT cohort (20.56±5.17 micrometer) compared to the auto-HCT cohort (16.19±3.31 micrometer; p<0.001) and healthy controls (14.66±2.61 micrometer; p<0.001). The median capillary density was significantly lower in the allo-HCT cohort (median: 6 capillaries/mm, range: 5-9 capillaries/mm) compared to the auto-HCT cohort (median: 8.5 capillaries, range: 5-12 capillaries/mm; p<0.001) and healthy controls (median: 8 capillaries/mm, range: 7-10.5 capillaries/mm; p<0.001). The allo-HCT cohort had a higher proportion of patients with significant neoangiogenesis (86%) than the auto-HCT cohort (10%) and healthy controls (9%). The presence of significant neoangiogenesis was more frequent in the subgroup of patients with a history of GVHD (93%) compared to the subgroup of patients without any history of GVHD (57%; p=0.044). No significant differences in NFVC parameters or FMD were observed between recipients of myeloablative and reduced-intensity conditioning regimens. There was no significant difference in NFVC parameters between the auto-HCT cohort and healthy controls. There was no significant difference in FMD among the three cohorts; however, a higher proportion of patients in the allo-HCT cohort (28%) had lower FMD than those in the auto-HCT cohort (3%) and healthy controls (6%), suggesting endothelial dysfunction. Conclusions: Our findings demonstrate the presence of structural microvasculopathy in allo-HCT recipients and suggest a possible role of alloreactivity in the pathogenesis of post-HCT microvasculopathy.

Role of chemokine receptors in transplant rejection and graft-versus-host disease.

Organ transplantation increases life expectancy and improves the quality of life of patients experiencing specific conditions such as terminal organ failure. Despite matching efforts between donor and recipient, immune activation can interfere with allograft survival after transplantation if immunosuppression is not used. With both innate and adaptive responses, this is a complicated immunological process. This can lead to organ rejection, or graft-versus-host disease (GVHD), depending on the origin of the immune response. Inflammatory factors, such as chemokine receptors and their ligands, are involved in a wide variety of immunological processes, including modulating transplant rejection or GVHD, therefore, chemokine biology has been a major focus of transplantation studies. These molecules attract circulating peripheral leukocytes to infiltrate into the allograft and facilitate dendritic and T cell trafficking between lymph nodes and the graft during the allogeneic response. In this chapter, we will review the most relevant chemokine receptors such as CXCR3 and CCR5, among others, and their ligands involved in the process of allograft rejection for solid organ transplantation and graft-versus-host disease in the context of hematopoietic cell transplantation.

CD19-chimeric antigen receptor-invariant natural killer T cells transactivate NK cells and reduce alloreactivity.

Invariant natural killer T (iNKT) cells are a small fraction of T lymphocytes with strong cytotoxic and immunoregulatory properties. We previously showed that human culture-expanded iNKT cells prevent alloreactivity and lyse primary leukemia blasts. Here, iNKT cells have several advantages over T cells based on their immunoregulatory capabilities. Since chimeric antigen receptors (CARs) increase the benefit of immune effector cells, they play a crucial role in improvement of cytotoxic abilities of novel cellular therapeutics such as iNKT cells. In the present study, we investigated transactivation of NK cells and prevention of alloreactivity through iNKT cells transduced with a CD19-directed CAR. iNKT cells were isolated by magnetic cell separation from peripheral blood mononuclear cells and transduced with a CD19-CAR retrovirus. Transduction efficiency, purity and cell subsets were measured by flow cytometry. Transactivation and cytotoxicity assays have been established to investigate the ability of CD19-CAR-iNKT cells to transactivate primary NK cells. A mixed lymphocyte reaction (MLR) was performed to explore the inhibition of alloreactive CD3+ T cells by CD19-CAR-iNKT cells. CD19-CAR-iNKT cells are able to transactivate NK cells independent of cell contact: The expression of activation marker CD69 was significantly increased and also production of the proinflammatory cytokine interferon-gamma was higher in NK cells pretreated with CD19-CAR-iNKT cells. Consequently, the cytotoxic activity of such NK cells was significantly increased being able to lyse leukemia cells more effectively than without prior transactivation. Adding CD19-CAR-iNKT cells to an MLR resulted in a decreased expression of the T cell activation marker CD25 on alloreactive CD3+ T lymphocytes stimulated with HLA mismatched dendritic cells. Also, the proliferation of alloreactive CD3+ T lymphocytes was significantly reduced in this setting. We demonstrate that CD19-CAR-iNKT cells keep their immunoregulatory properties despite transduction with a CAR making them an attractive effector cell population for application after allogeneic hematopoietic cell transplantation. By transactivating NK cells, increasing their cytotoxic activity and suppressing alloreactive T cells, they might further improve outcomes through prevention of both relapse and graft-versus-host disease.

Aspergillus calidoustus and Talaromyces columbinus infections in chronic graft-versus-host disease.

Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids. However, azole prophylaxis may cause resistant Aspergillus species like A. calidoustus, which are difficult to treat. We report a case from our institution where a patient developed a dual infection with Aspergillus calidoustus and Talaromyces columbinus after alloHSCT and posaconazole prophylaxis. While A. calidoustus is known to cause IFIs in HSCT recipients, T. columbinus represents a previously unreported occurrence in medical literature. This case underscores the importance of a multifaceted diagnostic strategy, integrating BAL diagnosis, mycological cultures, direct microscopy, fungal speciation, susceptibility testing, and biomarkers. These comprehensive approaches are indispensable for accurate pathogen identification and effective management of IFIs with appropriate antifungal agents.

Interventional antibiotic treatment replacing antibiotic prophylaxis during allogeneic hematopoietic stem cell transplantation is safe and leads to a reduction of antibiotic administration.

Patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) face an elevated risk of infection-related mortality, particularly during the pre-engraftment period. Although systemic antibiotic prophylaxis (SAP) is commonly employed during neutropenia, it is linked to disruptions in the intestinal microbiome, increasing the risk of graft-versus-host disease (GVHD), Clostridium difficile infection (CDI), and colonization with multi-drug resistant (MDR) bacteria. In our retrospective analysis, we evaluated the safety and efficacy of an exclusively interventional antibiotic treatment (IAT) compared to SAP in adult alloHSCT patients. In comparison to SAP, IAT resulted in a significantly reduced duration of antibiotic therapy (24 vs. 18 days, p < 0.001), although the cumulative incidence (CI) of bloodstream infections (BSI) by day + 100 post-HSCT was significantly higher in the IAT group compared to SAP (40% vs. 13%, p < 0.001). However, this did not lead to a significant increase in ICU transfers (13% vs. 6%, p = ns) or a higher CI of non-relapse mortality (NRM) at 3 years (11% vs. 10%, p = ns). With a median follow-up of 1052 days, the 3-year overall survival (OS) rates were 69% and 66% for the SAP and IAT cohorts, respectively (p = ns). The CI of acute GVHD grade II-IV (30% vs. 39%) at 100 days or chronic GVHD of any grade (50% vs. 45%) at 3 years did not differ significantly between the SAP and IAT groups. There was a tendency towards a higher CI of severe chronic GVHD in the SAP cohort (28% vs. 13%, p = 0.08). Our single center experience in conducting alloHSCT without antibiotic prophylaxis but with stringent guidelines for prompt antibiotic intervention demonstrated no disadvantages in terms of OS and NRM. IAT led to significantly reduced consumption of cefotaxime, carbapenem, and glycopeptide antibiotics. In conclusion, our findings suggest that replacing SAP with the proposed IAT procedure is both safe and feasible.

Population pharmacokinetic modeling of vedolizumab for graft-versus-host disease prophylaxis in adults with allogeneic hematopoietic stem cell transplant.

We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft-versus-host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open-label, dose-finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo-HSCT were analyzed using a two-compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time-varying covariates. Model selection was driven by goodness-of-fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo-HSCT, vedolizumab PK were well described by a two-compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab.

Immune isolation-enabled nanoencapsulation of donor T cells: a promising strategy for mitigating GVHD and treating AML in preclinical models.

BACKGROUND: In allogeneic-hematopoietic stem cell transplantation for acute myeloid leukemia (AML), donor T cells combat leukemia through the graft-versus-leukemia (GVL) effect, while they also pose a risk of triggering life-threatening graft-versus-host disease (GVHD) by interacting with recipient cells. The onset of GVHD hinges on the interplay between donor T cells and recipient antigen-presenting cells (APCs), sparking T-cell activation. However, effective methods to balance GVHD and GVL are lacking. METHODS: In our study, we crafted nanocapsules by layering polycationic aminated gelatin and polyanionic alginate onto the surface of T cells, examining potential alterations in their fundamental physiological functions. Subsequently, we established an AML mouse model and treated it with transplantation of bone marrow cells (BMCs) combined with encapsulated T cells to investigate the GVL and anti-GVHD effects of encapsulated T cells. In vitro co-culture was employed to probe the effects of encapsulation on immune synapses, co-stimulatory molecules, and tumor-killing pathways. RESULTS: Transplantation of BMCs combined with donor T cells selectively encapsulated onto AML mice significantly alleviates GVHD symptoms while preserving essential GVL effects. Encapsulated T cells exerted their immunomodulatory effects by impeding the formation of immune synapses with recipient APCs, thereby downregulating co-stimulatory signals such as CD28-CD80, ICOS-ICOSL, and CD40L-CD40. Recipient mice receiving encapsulated T-cell transplantation exhibited a marked increase in donor Ly-5.1-BMC cell numbers, accompanied by unaltered in vivo expression levels of perforin and granzyme B. While transient inhibition of donor T-cell cytotoxicity in the tumor microenvironment was observed in vitro following single-cell nanoencapsulation, subsequent restoration to normal antitumor activity ensued, attributed to selective permeability of encapsulated vesicle shells and material degradation. Moreover, the expression of apoptotic proteins and FAS-FAS ligand pathway at normal levels was still observed in leukemia tumor cells. CONCLUSIONS: Encapsulated donor T cells effectively mitigate GVHD while preserving the GVL effect by minimizing co-stimulatory signaling with APCs through early immune isolation. Subsequent degradation of nanocapsules restores T-cell cytotoxic efficacy against AML cells, mediated by cytotoxic pathways. Using transplant-encapsulated T cells offers a promising strategy to suppress GVHD while preserving the GVL effect.

Extracorporeal Photopheresis in Pediatric and Adult Patients with Graft-Versus-Host Disease.

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.

Differences in Acute Graft-Versus-Host Disease (GVHD) Severity and Its Outcomes Between Black and White Patients.

Acute graft-versus-host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation (HCT). Although recent advancements in GVHD prophylaxis have resulted in successful HCT across HLA barriers and expanded access to HCT for racial minorities, less is known about how race affects the severity and outcomes of acute GVHD. This study examines differences in the clinical course of acute GVHD and the prognostic value of GVHD biomarkers for Black and White recipients. We conducted a retrospective analysis of patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) database who underwent HCT between 2014 and 2021 to describe the difference in clinical course of acute GVHD and significance of GVHD biomarkers between Black and White recipients. We used propensity score matching to generate a 1:3 matched cohort of 234 Black patients and 702 White patients with similar baseline characteristics. In the first year after HCT Black patients experienced a higher cumulative incidence of grade III-IV acute GVHD (17% versus 12%, P = 0.050), higher nonrelapse mortality (NRM; 18% versus 12%, P = .009), and lower overall survival that trended toward statistical significance (73% versus 79%, P = .071) compared to White patients. The difference in NRM in the first year was even greater among Black patients who developed GVHD than White patients (24% versus 14%, P = .041). The distribution of low, intermediate, and high MAGIC biomarker scores at the time of treatment was similar across racial groups (P = .847), however, Black patients with high biomarker scores experienced significantly worse NRM than White patients (71% versus 32%, P = .010). Our data indicate that Black patients are at a higher risk of NRM following HCT, primarily from a higher incidence of severe GVHD. Serum biomarkers at treatment initiation can stratify patients for risk of NRM across races, however Black patients with high biomarker scores had a significantly greater NRM risk. These results suggest a need for strategies that mitigate the higher risk for poor GVHD outcomes among Black patients.

Antibiotic Prophylaxis During Allogeneic Stem Cell transplantation-A Comprehensive Single Center Retrospective Analysis.

BACKGROUND: Prophylactic antibiotics are still controversial during allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our transplant center, we suspended antibiotic prophylaxis during allo-HSCT in 2017. OBJECTIVE: The main objective of this study was the detailed analysis of the potentially beneficial impact of omittance of standard antibiotic prophylaxis during allo-HSCT in survival and Graft-versus-Host disease (GvHD) development, especially with consideration of confounding factors and competing events. Secondary objectives were the evaluation of the risk of severe infections and transplant-related mortality without antibiotic prophylaxis, the detailed assessment of bacterial and viral infections including multiresistant pathogens as well as occurrence of relapse in both groups. This study aims to support the development of future antibiotic strategies in allo-HSCT. STUDY DESIGN: We retrospectively analyzed patient outcome in the time periods before (between December 2012 and February 2017) and after suspension (between March 2017 and June 2020) of antibiotic prophylaxis during allo-HSCT. Relevant clinical outcome parameters of the patients (n = 221) were collected by chart-review in the two groups (with antibiotic prophylaxis n = 101 versus without antibiotic prophylaxis n = 120). All patients were 18 years or older. Propensity score methods were used to adjust for potentially confounding patient characteristics. To address competing events, transitions between moderate/severe acute and chronic GvHD, relapse and death were analyzed using an inverse-propensity score weighted multistate modeling approach. RESULTS: While we observed a trend towards an improved outcome in the cohort without antibiotic prophylaxis, the inverse-propensity-score-weighted analyses did not show significant differences between the two groups in overall survival (OS) (P = .811) or development of acute GvHD (aGvHD) grade 3/4 (P = .158) and chronic moderate/severe GvHD (cGvHD) (P = .686). Multistate analysis respecting competing events revealed comparable estimated probabilities without antibiotic prophylaxis versus with antibiotic prophylaxis in OS (35.0% [95% CI: 28.2%-42.7%] versus 35.3% [95% CI: 27.8%-41.1%]) as well as development of aGvHD grade 3/4 (7.7% [95% CI: 5.9%-12.2%] vs. 10.6% [95% CI: 7.7%-15.7%]) and moderate/severe cGvHD (21.0% [95% CI: 17.7%-30.0%] vs. 23.8% [95% CI: 19.6%-31.4%]). Similar analyses showed also no significant differences in relapse rate, transplant-related mortality, relapse-related mortality, or GvHD-free/relapse-free survival between the two groups. An observed increase in severe infections without antibiotic prophylaxis did not lead to a significantly higher mortality rate. Viral reactivation and detection of multiresistant bacteria were comparable, yet a higher incidence of Clostridioides difficile infections was observed in patients receiving antibiotic prophylaxis. CONCLUSION: Our study supports previous reports of noninferiority of allo-HSCT without use of antibiotic prophylaxis with close monitoring and rapid intervention, if infection is suspected. The trend towards improved outcomes without antibiotic prophylaxis, however, might not only be due to the absence of antibiotic prophylaxis but also due to additional progresses in the field over the recent years. While the present study is too small to draw definite conclusions, these results strongly warrant further multicenter studies addressing the potential benefit of omitting antibiotic prophylaxis during allo-HSCT.