National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report

Wolff, Daniel; Radojčić, Vedran; Lafyatis, Robert; Çınar, Reşat; Rosenstein, Rachel K.; Cowen, Edward W.; Cheng, Guang‐Shing; Sheshadri, Ajay; Bergeron, Anne; Williams, Kirsten M.; Todd, Jamie L.; Teshima, Takanori; Cuvelier, Geoffrey D.E.; Holler, Ernst; McCurdy, Shannon R.; Jenq, Robert R.; Hanash, Alan M.; Jacobsohn, David A.; Santomasso, Bianca; Jain, Sandeep; Ogawa, Yoko; Steven, Philipp; Luo, Zhonghui; Dietrich-Ntoukas, Tina; Saban, Daniel R.; Bilić, Ervina; Penack, Olaf; Griffith, Linda M.; Cowden, Meredith; Martin, Paul J.; Greinix, Hildegard; Sarantopoulos, Stefanie; Socié, Gérard; Blazar, Bruce R.; Pidala, Joseph; Kitko, Carrie L.; Couriel, Daniel R.; Cutler, Corey; Schultz, Kirk R.; Pavletić, Steven Z.; Lee, Stephanie J.; Paczesny, Sophie

doi:10.1016/j.jtct.2021.06.001

Cited by 70 publications

(150 citation statements)

References 254 publications

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“…In conclusion, we reported the early pathophysiological changes in the cornea of an established cGVHD mouse model by IVCM. An NIH Consensus Conference suggested the importance of early diagnosis for GVHD [35], and many researchers have since focused on the ocular symptoms of GVHD [36]. Since IVCM is approved for clinical examination in patients, it should prove to be a powerful tool in the early diagnosis and treatment in order to prevent GVHD-related DED.…”

Section: Discussionmentioning

confidence: 99%

Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy

et al. 2021

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Graft-versus-host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT), and ocular GVHD can cause severe dry eye disease that can lead to visual impairment. Epithelial damage, vascular invasion, corneal fibrosis, and corneal perforation may occur in severe cases. It is generally accepted that inflammatory cells such as dendritic cells and T cells contribute to this pathological condition. However, it is still unknown what pathological condition occurs on the ocular surface after HSCT, and when. We therefore observed the dynamics of inflammatory cells in the cornea of chronic GVHD (cGVHD) model mice from 1 to 4 weeks after bone marrow transplantation (BMT) by in vivo confocal microscopy (IVCM) and considered the relationship with the pathophysiology of ocular GVHD (tear volume, corneal epithelial damage). In the allogeneic group, neovascularization occurred in all eyes at 1 week after BMT, although almost all vessels disappeared at 2 weeks after BMT. In addition, we revealed that infiltration of globular cells, and tortuosity and branching of nerves in the cornea occurred in both cGVHD mice and human cGVHD patients. Thus, we consider that cGVHD mouse model study by IVCM reproduces the state of ocular GVHD and may contribute to elucidating the pathological mechanism for ocular GVHD.

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Section: Discussionmentioning

confidence: 99%

Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy

et al. 2021

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“…Notably, the use of murine experimental aHSCT models has observed ophthalmic manifestations, such that analysis of potential correlation with dermatologic changes can be investigated [ 14 , 15 , 16 ]. It is well established that different pre-clinical mouse HSCT models as observed in patients after aHSCT exhibit varying levels of GVHD severity in different target compartments, including the gastrointestinal tract, lungs, as well as the eye and skin [ 36 , 37 , 38 , 39 ]. Since both the ocular and skin compartments contain an important epithelial cell layer directly exposed to environmental stresses, we considered the notion that GVHD might similarly affect both of these tissues and employed pre-clinical HSCT to examine if any correlation could be identified.…”

Section: Discussionmentioning

confidence: 99%

Analyses and Correlation of Pathologic and Ocular Cutaneous Changes in Murine Graft versus Host Disease

Levy

Mousa

Lightbourn

et al. 2021

IJMS

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Graft versus host disease (GVHD) is initiated by donor allo-reactive T cells activated against recipient antigens. Chronic GVHD (cGVHD) is characterized by immune responses that may resemble autoimmune features present in the scleroderma and Sjogren’s syndrome. Unfortunately, ocular involvement occurs in approximately 60–90% of patients with cGVHD following allo-hematopoietic stem cell transplants (aHSCT). Ocular GVHD (oGVHD) may affect vision due to ocular adnexa damage leading to dry eye and keratopathy. Several other compartments including the skin are major targets of GVHD effector pathways. Using mouse aHSCT models, the objective was to characterize cGVHD associated alterations in the eye and skin to assess for correlations between these two organs. The examination of multiple models of MHC-matched and MHC-mismatched aHSCT identified a correlation between ocular and cutaneous involvement accompanying cGVHD. Studies detected a “positive” correlation, i.e., when cGVHD-induced ocular alterations were observed, cutaneous compartment alterations were also observed. When no or minimal ocular signs were detected, no or minimal skin changes were observed. In total, these findings suggest underlying cGVHD-inducing pathological immune mechanisms may be shared between the eye and skin. Based on the present observations, we posit that when skin involvement is present in aHSCT patients with cGVHD, the evaluation of the ocular surface by an ophthalmologist could potentially be of value.

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“…Similar approaches are of high interest for patients with fibrotic manifestations of chronic GVHD. 64 …”

Section: Future Directionsmentioning

confidence: 99%

Recent FDA Approvals in the Treatment of Graft-Versus-Host Disease

2022

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Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT) and is associated with significant morbidity and mortality. For many years, there have been few effective treatment options for patients with GVHD. First-line systemic treatment remains corticosteroids, but up to 50% of patients will develop steroid-refractory GVHD and the prognosis for these patients is poor. Elucidation of the pathophysiological mechanisms of acute and chronic GVHD has laid a foundation for novel therapeutic approaches. Since 2017, there have now been 4 approvals by the US Food and Drug Administration (FDA) for GVHD. Ruxolitinib, an oral selective JAK1/2 inhibitor, received FDA approval for the treatment of steroid-refractory acute GVHD in 2019 and remains the only agent approved for acute GVHD. There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy. In this review, we highlight the clinical data which support these FDA approvals in acute and chronic GVHD with a focus on mechanism of actions, clinical efficacy, and toxicities associated with these agents.

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National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report

Cited by 70 publications

References 254 publications

Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy

Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy

Analyses and Correlation of Pathologic and Ocular Cutaneous Changes in Murine Graft versus Host Disease

Recent FDA Approvals in the Treatment of Graft-Versus-Host Disease

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