Search

Background: Steroid-resistant (SR) lower gastrointestinal (LGI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of vedolizumab in the treatment of SR-LGI acute GVHD (aGVHD) remains uncertain. We aimed to assess the efficacy and safety of vedolizumab combined with basiliximab as second-line therapy for SRLGI-aGVHD. Methods: This study aimed to explore the efficacy of vedolizumab combined with basiliximab for SR-LGI-aGVHD. The primary endpoint was the overall response (OR) on day 28. Secondary and safety endpoints included durable OR at day 56, overall survival (OS), chronic GVHD (cGVHD), non-relapse mortality (NRM), failure-free survival (FFS), and adverse events. Results: Twenty-eight patients with SR-LGI-aGVHD were included. The median time to start of combination therapy after SR-LGI-aGVHD diagnosis was 7 (range, 4-16) days. The overall response rate (ORR) at 28 days was 75.0% (95% CI: 54.8%-88.6%), and 18 achieved a complete response (CR) (64.3%, 95% CI: 44.1%-80.7%). The durable OR at day 56 was 64.3% (95% CI: 44.1%-80.7%). The 100-day, 6-month, and 12-month OS rates for the entire cohort of patients were 60.7% (95% CI: 45.1%-81.8%), 60.7% (95% CI: 45.1%-81.8%), and 47.6% (95% CI: 31.4%-72.1%), respectively. The median failure-free survival was 276 days; (95% CI: 50-not evaluable) 12-month NRM was 42.9% (95% CI: 24.1%-60.3%). The 1-year cumulative incidence of cGVHD was 35.7%. Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections. Nine (32.1%) patients developed cytomegalovirus (CMV) reactivation complicated with bacterial infections (25.0%, CMV infection; 7.1%, CMV viremia). Epstein-Barr virus (EBV) reactivation occurred in five patients (17.9%, 95% CI: 6.8%-37.6%). Only three patients (10.7%, 95% CI: 2.8%-29.4%) in our study developed pseudomembranous colitis. Conclusions: Vedolizumab plus basiliximab demonstrated efficacy in severe SRLGI-aGVHD and was well-tolerated. Vedolizumab plus basiliximab may be considered a potential treatment option for patients with LGI-aGVHD. [ABSTRACT FROM AUTHOR]

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

BACKGROUND: Acute graft-versus-host disease (aGVHD) is a significant complication for patients who receive allogeneic stem cell transplantation. Patients whose aGVHD is refractory to corticosteroids face additional complications. OBJECTIVES: This article provides foundational knowledge on steroid-refractory (SR) aGVHD, current treatment options, and related supportive care. METHODS: Therapies for patients with SR aGVHD are summarized, along with supportive care recommendations and a review of related nursing considerations. FINDINGS: Current treatment and research on SR aGVHD offer opportunities for improved clinical outcomes for these patients. Nursing knowledge of the pathophysiology, treatment, and supportive care for patients with SR aGVHD is integral to the provision of optimal nursing care for a complex population of patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a significant complication for patients who receive allogeneic hematopoietic stem cell transplantation. This disease is further complicated for patients who are refractory to steroids. This article reviews emerging therapies and supportive care for patients with steroid-refractory cGVHD. OBJECTIVES: This article provides foundational knowledge on steroid-refractory cGVHD, emerging treatment options, and related supportive care. METHODS: Current research on emerging therapies for patients with steroid-refractory cGVHD is summarized along with supportive care recommendations and a review of related nursing considerations. FINDINGS: Emerging therapies for steroidrefractory cGVHD offer opportunities for improved clinical outcomes for these patients. Nursing knowledge of new therapies and supportive care for patients with steroid-refractory cGVHD supports the provision of optimal nursing care for a complex population of patients. [ABSTRACT FROM AUTHOR]

Abstract Acute graft-versus-host disease (aGVHD), especially intestinal aGVHD, is one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) has been applied to the treatment of intestinal steroid-refractory aGVHD (SR-aGVHD). Ruxolitinib is the first drug recommended for SR-aGVHD. Here, we reported the outcome data from 21 patients who had received the combined treatment of FMT with ruxolitinib as a salvage treatment in intestinal SR-aGVHD after HSCT. The overall response rate on day 28 was 71.4% (95% CI 50.4–92.5%), including 10 patients with complete responses. The durable overall response at day 56 in responders was 80%. GVHD relapse rate was 33.3% in responders. The levels of inflammatory cytokines as well as T cells and NK cells activation declined. The diversity of the intestinal microbiota was improved in responders. Viral reactivations and severe cytopenia were the major adverse events (61.9% and 81% respectively). The estimated 6-month overall survival was 57.1% (95% CI: 35.9–78.3%), while event-free survival was 52.4% (95% CI: 21.7%-64.1%). Collectively, FMT with ruxolitinib could be an effective treatment for intestinal SR-aGVHD after HSCT. Trial registration: ClinicalTrials.gov identifier: NCT03148743.

Acute graft-versus-host disease (aGVHD), especially intestinal aGVHD, is one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) has been applied to the treatment of intestinal steroid-refractory aGVHD (SR-aGVHD). Ruxolitinib is the first drug recommended for SR-aGVHD. Here, we reported the outcome data from 21 patients who had received the combined treatment of FMT with ruxolitinib as a salvage treatment in intestinal SR-aGVHD after HSCT. The overall response rate on day 28 was 71.4% (95% CI 50.4–92.5%), including 10 patients with complete responses. The durable overall response at day 56 in responders was 80%. GVHD relapse rate was 33.3% in responders. The levels of inflammatory cytokines as well as T cells and NK cells activation declined. The diversity of the intestinal microbiota was improved in responders. Viral reactivations and severe cytopenia were the major adverse events (61.9% and 81% respectively). The estimated 6-month overall survival was 57.1% (95% CI: 35.9–78.3%), while event-free survival was 52.4% (95% CI: 21.7%-64.1%). Collectively, FMT with ruxolitinib could be an effective treatment for intestinal SR-aGVHD after HSCT. Trial registration: ClinicalTrials.gov identifier: NCT03148743. [ABSTRACT FROM AUTHOR]

Background: Steroid-resistant (SR) lower gastrointestinal (LGI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of vedolizumab in the treatment of SR-LGI acute GVHD (aGVHD) remains uncertain. We aimed to assess the efficacy and safety of vedolizumab combined with basiliximab as second-line therapy for SR-LGI-aGVHD., Methods: This study aimed to explore the efficacy of vedolizumab combined with basiliximab for SR-LGI-aGVHD. The primary endpoint was the overall response (OR) on day 28. Secondary and safety endpoints included durable OR at day 56, overall survival (OS), chronic GVHD (cGVHD), non-relapse mortality (NRM), failure-free survival (FFS), and adverse events., Results: Twenty-eight patients with SR-LGI-aGVHD were included. The median time to start of combination therapy after SR-LGI-aGVHD diagnosis was 7 (range, 4-16) days. The overall response rate (ORR) at 28 days was 75.0% (95% CI: 54.8%-88.6%), and 18 achieved a complete response (CR) (64.3%, 95% CI: 44.1%-80.7%). The durable OR at day 56 was 64.3% (95% CI: 44.1%-80.7%). The 100-day, 6-month, and 12-month OS rates for the entire cohort of patients were 60.7% (95% CI: 45.1%-81.8%), 60.7% (95% CI: 45.1%-81.8%), and 47.6% (95% CI: 31.4%-72.1%), respectively. The median failure-free survival was 276 days; (95% CI: 50-not evaluable) 12-month NRM was 42.9% (95% CI: 24.1%-60.3%). The 1-year cumulative incidence of cGVHD was 35.7%. Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections. Nine (32.1%) patients developed cytomegalovirus (CMV) reactivation complicated with bacterial infections (25.0%, CMV infection; 7.1%, CMV viremia). Epstein-Barr virus (EBV) reactivation occurred in five patients (17.9%, 95% CI: 6.8%-37.6%). Only three patients (10.7%, 95% CI: 2.8%-29.4%) in our study developed pseudomembranous colitis., Conclusions: Vedolizumab plus basiliximab demonstrated efficacy in severe SR-LGI-aGVHD and was well-tolerated. Vedolizumab plus basiliximab may be considered a potential treatment option for patients with LGI-aGVHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Fan, Liu, Ye, Zeng, Xuan, Huang, Lin, Sun, Liu and Xu.)

Introduction: Acute graft-versus-host disease (aGVHD) is a significant immune-mediated complication of allogeneic hematopoietic stem cell transplant (HSCT). Despite prophylactic immunosuppression, the incidence of grades II–IV aGVHD post-HSCT varies from 20 to 80%. Tumor necrosis factor (TNF) is an important cytokine involved in the pathogenesis of GVHD, and medications such as infliximab (Remicade®) have been utilized as second-line treatment options in patients with steroid-refractory GHVD. Infliximab-dyyb (Inflectra®) and infliximab-qbtx (Ixifi®) are biosimilars approved by the FDA for a variety of autoimmune disorders. This is the first case report documenting the utility of infliximab-dyyb and -qbtx for the management of steroid-refractory aGVHD. Case report: We report the post-transplant course of three patients treated with infliximab biosimilars as a part of therapy for management of steroid-refractory aGVHD. Management and outcome: Steroid-refractory aGVHD is associated with poor prognosis and its management, as highlighted in our three patient cases, and can be very diverse often requiring different therapeutic modalities which overlap in administration. Discussion: In these patients with steroid-refractory aGVHD, we were able to show that infliximab biosimilars could be used in lieu of the reference infliximab product. Although we had important limitations, this case report supports the use of anti-TNF agents in highly mortal steroid-refractory acute GI GVHD and that replacement of infliximab with its biosimilars is feasible. [ABSTRACT FROM AUTHOR]

Abstract Background Graft-versus-Host Disease (GvHD) causes significant morbidity and mortality in patients after allogeneic stem cell transplantation. Donor T-cells cause inflammation and tissue damage in GvHD target organs such as liver, gut and skin. Cytokine receptor associated kinases JAK1 and JAK2 are critical for inflammatory cytokine response in GvHD. Ruxolitinib is a small molecule inhibitor of JAK1 and JAK2. Preliminary data indicated substantial clinical activity in patients with steroid-refractory (SR) acute and chronic GvHD. Methods The RIG-study is an investigator-initiated open-label, multicenter, prospective randomized controlled two-arm phase 2 study, comparing the efficacy of ruxolitinib and best available treatment (BAT) versus BAT in steroid-refractory acute GvHD (SR-aGvHD). Patients with acute skin, intestinal or liver GvHD > grade 1 and failure of previous treatment are eligible. The trial aims to include 160 patients who will be randomized in a 1:1 ratio and stratified by GvHD grade (≤ grade 3 versus grade 4) and number of previous immunosuppressive treatments (≤ 3 versus ≥4). The primary endpoint is the overall response rate at day 28, defined as: Improvement of at least one stage in the severity of acute GvHD in one organ without deterioration in any other organ, or disappearance of any GvHD signs from all organs without requirement for new systemic immunosuppressive treatment. Secondary objectives include time to response, overall survival, event-free survival, non-relapse mortality (NRM), failure-free survival, graft failure rates, quality of life and changes in serum levels of pro-inflammatory cytokines and GvHD-related biomarkers. Discussion This randomized prospective trial will provide further evidence if the retrospectively collected data demonstrating activity of ruxolitinib for SR-aGvHD can be reproduced. A major advantage of ruxolitinib might be the limited and predictable toxicity profile compared to other immunosuppressive therapies that mainly includes viral reactivation and cytopenias. This trial will establish candidate biomarkers to predict and monitor responses to ruxolitinib. As a next step ruxolitinib might be tested upfront against steroids or in a preemptive manner to prevent GvHD to occur. Trial registration NCT02396628 (registration date 17.07.2015); DRKS00007939 (registration date 26.03.2015).

Taxonomic composition of the gut microbiota at the time of neutrophil engraftment is associated with the development of acute gastrointestinal graft-versus-host disease (GI GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation. However, less is known about the relationship between the gut microbiota and development of steroid-refractory GI GVHD immediately before the onset of disease. Markers of steroid-refractory GI GVHD are needed to identify patients who may benefit from the early initiation of non-corticosteroid-based GVHD treatment. Our aim was to identify differences in taxonomic composition in stool samples from patients without GVHD, with steroid-responsive GVHD and with steroid-refractory GI GVHD to identify predictive microbiome biomarkers of steroid-refractory GI GVHD. We conducted a retrospective case-control, single institution study, performing shotgun metagenomic sequencing on stool samples from patients with (n = 36) and without GVHD (n = 34) matched for time since transplantation. We compared the taxonomic composition of the gut microbiome in those with steroid-sensitive GI GVHD (n = 17) and steroid-refractory GI GVHD (n = 19) to each other and to those without GVHD. We also performed associations between steroid-refractory GI GVHD, gut taxonomic composition, and fecal calprotectin, a marker of GI GVHD to develop composite fecal markers of steroid-refractory GVHD before the onset of GI disease. We found that fecal samples within 30 days of GVHD onset from patients with and without GVHD or with and without steroid-refractory GI GVHD did not differ significantly in Shannon diversity (alpha-diversity) or in overall taxonomic composition (beta-diversity). Although those patients without GVHD had higher relative abundance of Clostridium spp., those with and without steroid-refractory GI GVHD did not significantly differ in taxonomic composition between one another. In our study, fecal calprotectin before disease onset was significantly higher in patients with GVHD compared to those without GVHD and higher in patients with steroid-refractory GI GVHD compared to steroid-sensitive GI GVHD. No taxa were significantly associated with higher levels of calprotectin., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Graft-versus-Host Disease (GvHD) causes significant morbidity and mortality in patients after allogeneic stem cell transplantation. Donor T-cells cause inflammation and tissue damage in GvHD target organs such as liver, gut and skin. Cytokine receptor associated kinases JAK1 and JAK2 are critical for inflammatory cytokine response in GvHD. Ruxolitinib is a small molecule inhibitor of JAK1 and JAK2. Preliminary data indicated substantial clinical activity in patients with steroid-refractory (SR) acute and chronic GvHD.Methods: The RIG-study is an investigator-initiated open-label, multicenter, prospective randomized controlled two-arm phase 2 study, comparing the efficacy of ruxolitinib and best available treatment (BAT) versus BAT in steroid-refractory acute GvHD (SR-aGvHD). Patients with acute skin, intestinal or liver GvHD > grade 1 and failure of previous treatment are eligible. The trial aims to include 160 patients who will be randomized in a 1:1 ratio and stratified by GvHD grade (≤ grade 3 versus grade 4) and number of previous immunosuppressive treatments (≤ 3 versus ≥4). The primary endpoint is the overall response rate at day 28, defined as: Improvement of at least one stage in the severity of acute GvHD in one organ without deterioration in any other organ, or disappearance of any GvHD signs from all organs without requirement for new systemic immunosuppressive treatment. Secondary objectives include time to response, overall survival, event-free survival, non-relapse mortality (NRM), failure-free survival, graft failure rates, quality of life and changes in serum levels of pro-inflammatory cytokines and GvHD-related biomarkers.Discussion: This randomized prospective trial will provide further evidence if the retrospectively collected data demonstrating activity of ruxolitinib for SR-aGvHD can be reproduced. A major advantage of ruxolitinib might be the limited and predictable toxicity profile compared to other immunosuppressive therapies that mainly includes viral reactivation and cytopenias. This trial will establish candidate biomarkers to predict and monitor responses to ruxolitinib. As a next step ruxolitinib might be tested upfront against steroids or in a preemptive manner to prevent GvHD to occur.Trial Registration: NCT02396628 (registration date 17.07.2015); DRKS00007939 (registration date 26.03.2015). [ABSTRACT FROM AUTHOR]

Currently, steroid-refractory severe gastrointestinal (GI) graft versus host disease (GVHD) is among the most important complications of allogeneic transplantation, and as yet there is no standard approach to its treatment. Herein we report two cases with steroid-refractory GI GVHD that received intramesenteric steroid treatment. In both cases the frequency and volume of diarrhea resolved completely following intramesenteric methylprednisolone (MP) injection. In conclusion, intra-arterial steroid injection might be an alternative treatment approach for steroid-refractory GI GVHD. [ABSTRACT FROM AUTHOR]

Acute GVHD (aGVHD) remains a major cause of mortality in patients undergoing allo-SCT. In particular, the outcome of those patients who fail first-line therapy with glucocorticosteroids is poor. Preliminary reports suggested that the purine analogue pentostatin might be effective for treatment of steroid-refractory aGVHD. Here, we report on our single-center experience with pentostatin in this condition. From 2005 to 2008, a total of 24 consecutive patients, who had undergone first-line salvage treatment for steroid-refractory aGVHD of the gastrointestinal tract with pentostatin, were identified from 301 patients allografted during that period and retrospectively analyzed. Response to treatment, defined as CR or very good PR (VGPR), was observed in nine patients (38%), with a median time to response of 10 days. Although pentostatin was associated with only moderate myelosuppressive toxicity, if any, 2-year survival was only 17% with five of the nine responders dying from infection (four patients) or recurrent GVHD (one patient). We conclude that pentostatin is a moderately effective therapy for steroid-refractory aGVHD, showing response and outcome rates similar to other clinically used regimens. [ABSTRACT FROM AUTHOR]

Haplo-identical stem cell transplantation (haplo-SCT) for hematological malignancies has ushered in a new era in which everyone has a potential donor. However, the occurrence of steroid-refractory acute graft-versus-host disease (SR-aGVHD), with no priority among second-line therapies, leads to late mortality after haplo-SCT. Ruxolitinib is the first drug recommended for SR-aGVHD. Here, we report the outcome data from 40 patients after haplo-SCT following the Beijing Protocol who had received ruxolitinib as a salvage therapy for grades II to IV SR-aGVHD in our center between November 2017 and May 2019. The overall response rate was 85% (34/40; 95% confidence interval [CI], 73.4% to 96.6%), including 25 patients with complete response. The median time to first response was 10 days. The levels of inflammatory cytokines and T cell activation declined, and the percentage of regulatory T cells increased. The rate of GVHD relapse was 26.5% (9/34; 95% CI, 10.8% to 42.1%) in responders. Cytomegalovirus reactivation and cytopenia were the major adverse events after ruxolitinib was begun (57.5% and 60%, respectively). The 6-month overall survival estimate was 56.8% (95% CI, 41.5% to 72.1%), and the event-free survival was 45% (95% CI, 29.7% to 60.3%). Liver GVHD was associated with a worse response rate and poor survival. Collectively, ruxolitinib could be an effective treatment for SR-aGVHD patients after haplo-SCT., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Steroid-refractory (SR) lower gastrointestinal (LGI) acute graft-versus-host disease (aGVHD) has poor prognosis, and novel drugs are needed. We describe outcomes of patients with SR-LGI aGVHD treated with vedolizumab. The primary objective was to determine overall response rate (ORR) at days 14, 28, and 56. Secondary outcomes included overall survival (OS), non-relapse mortality and toxicities. Twenty patients, median age 46 years (range, 23-71), were included. All but 2 patients (90%) had grade 3 to 4 aGVHD (45% stage 4, 40% stage 3 LGI). Median time to vedolizumab was 21 days (range, 5-1031) and 13 days (range, 0-533) after diagnosis of LGI aGVHD and SR-LGI aGVHD, respectively. It was given as ≥3rd line (median 3; range 2-6) in 75% after failure of steroids, and additional treatments including ruxolitinib (n = 12) and others. Median follow-up was 17 months (range, 10-34). The days 14, 28 and 56 ORRs were 45% (9/20; complete response [CR] 25%), 35% (7/20; CR 20%), and 25% (5/20; CR 20%), respectively. Among ruxolitinib failures, it was 50% (6/12; CR 25%), 50% (6/12; CR 25%) and 25% (3/12; CR 16.7%), respectively. Fifteen patients died (14 GVHD, 1 leukemia relapse). The actuarial 6-month OS was 35% (95% confidence interval 16-55). No progressive multifocal leukoencephalopathy or infusion reaction occurred. Forty-four infection events (22 viral, 18 bacterial, and 4 fungal) were noted in 16 patients. Vedolizumab was well tolerated and demonstrated potential efficacy even after ruxolitinib failure for SR-LGI aGVHD. Yet the responses were suboptimal, and its use requires further investigation., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: Graft-versus-host disease (GVHD) continues to be the major lethal complication of allogeneic hematopoietic stem cell transplantation (HCT) but the standard of care, high dose steroids, has not changed in 40 years. Approximately 50% of GVHD patients will develop steroid refractory disease, typically involving the gastrointestinal (GI) tract, which has a very poor prognosis. Newly developed GVHD biomarker-based risk scores provide the first opportunity to treat patients at the onset of symptoms according to risk of steroid failure. Furthermore, improvements in our understanding of the pathobiology of GVHD, its different signaling pathways, involved cytokines, and the role of post-translational and epigenetic modifications, has identified new therapeutic targets for clinical trials., Areas Covered: This manuscript summarizes the pathophysiology, diagnosis, staging, current and new targeted therapies for GVHD, with an emphasis on GI GVHD. A literature search on PubMed was undertaken and the most relevant references included., Expert Opinion: The standard treatment for GVHD, high dose steroids, offers less than optimal outcomes as well as significant toxicities. Better treatments, especially for GI GVHD, are needed to reduce non-relapse mortality after allogeneic HCT. The identification of high risk patients through a biomarker-defined scoring system offers a personalized approach to a disease that still requires significant research attention., Competing Interests: Declaration of interest J Ferrara and J Levine both own a patent on GVHD biomarkers. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.