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

2021 ◽  
Vol 23 (1) ◽  
pp. 184
Author(s):  
Robert B. Levy ◽  
Hazem M. Mousa ◽  
Casey O. Lightbourn ◽  
Eric J. Shiuey ◽  
David Latoni ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Ocular Involvement ◽  
Hematopoietic Stem ◽  
Skin Changes ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Transplants ◽  
Effector Pathways ◽  
Hematopoietic Stem Cell Transplants

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.

scholarly journals Mast Cell Involvement in Fibrosis in Chronic Graft-Versus-Host Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2385
Author(s):  
Ethan Strattan ◽  
Gerhard Carl Hildebrandt
Keyword(s):  
Wound Healing ◽  
Mast Cell ◽  
Mast Cells ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Fibrotic Disease ◽  
Acute Leukemias ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead to fibrotic disease. Interestingly, in chronic GVHD, aberrant wound healing mechanisms lead to pathological fibrosis, but the cellular etiology driving this is not well-understood, although some studies have implicated mast cells. Given this novel role, we here review the literature for studies of mast cell involvement in the context of chronic GVHD. While there are few publications on this topic, the papers excellently characterized a niche for mast cells in chronic GVHD. These findings may be extended to other fibrosing diseases in order to better target mast cells or their mediators for treatment of fibrotic disease.

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

scholarly journals Ruxolutinib in Steroid Refractory Graft Versus Host Disease (SR-GVHD): Systemic Literature Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5682-5682
Author(s):  
Mostafa F. Mohammed Saleh ◽  
Shahrukh K. Hashmi
Keyword(s):  
Adverse Events ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Systemic Review ◽  
Close Monitoring ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory

Background: Graft versus host disease (GVHD) is a main cause of morbidity and mortality in patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT). About 30-40% of patients have steroid‐refractory GVHD (SR‐GVHD) after the first‐line use of high doses of corticosteroids with a poor prognosis .Ruxolitinib is a promising treatment for SR-GVHD. However, data regarding optimum dosing, response rates and associated adverse events are scarce. Herein, we provide the first systemic review of literature for the use ruxolutinib in GVHD. Methods: A Medline (PubMed), google scholar, OVID and Cochrane Database of Systematic Reviews search using key words "Ruxolutinib and GVHD", "Ruxolutinib and SR-GVHD" was undertaken in June 2019. Only peer reviewed databases were searched and search was restricted to human studies of acute and chronic GVHD only. Results: 16 publications, as listed in Table 1. Only one was a prospective trial, all others were retrospective studies, case series (5), and case reports (2). Overall response, ranged 45% - 100%, complete response was noted in 5.2% -80% patients. Time to response was variable from 1-12 weeks. Cytopenias and infectious complications were frequently reported with dose reduction or interruptions needed in most studies. Maintained responses were reported in a small proportion after ruxolutinib discontinuation. Conclusion Ruxolutinib has promising efficacy in SR-GVHD , however cytopenias and infectious complications reported frequently mandate close monitoring. Results of ongoing prospective trials could provide answers for optimum dosing and response assessment, and management of related adverse events. Table Disclosures No relevant conflicts of interest to declare.

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3683-3686 ◽  
Author(s):  
Samar Kulkarni ◽  
Ray Powles ◽  
Jennie Treleaven ◽  
Unell Riley ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Pneumococcal Infection ◽  
Pneumococcal Infections ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Penicillin Prophylaxis

Abstract Incidences of and risk factors for Streptococcus pneumoniaesepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P = .03) and chronic GVHD (10-year probability, 14% vs 4%; P = .002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127;P = .07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16;P = .04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk.

scholarly journals Adverse events in second- and third-line treatments for acute and chronic graft-versus-host disease: systematic review

2020 ◽  
Vol 11 ◽  
pp. 204062072097703
Author(s):  
Vladica M. Velickovic ◽  
Emily McIlwaine ◽  
Rongrong Zhang ◽  
Tim Spelman
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Pharmaceutical Management ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Third Line

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of graft- versus-host disease (GvHD), a strong prognostic predictor of early mortality within the first 2 years following allo-HSCT. The objective of this study was to describe the harm outcomes reported among patients receiving second- and third-line treatment as part of the management for GvHD via a systematic literature review. Methods: A total of 34 studies met the systematic review inclusion criteria, reporting adverse events (AEs) across 12 different second- and third-line therapies. Results: A total of 14 studies reported AEs across nine different therapies used in the treatment of acute GvHD (aGvHD), 17 studies reported AEs of eight different treatments for chronic GvHD (cGvHD) and 3 reported a mixed population. Infections were the AE reported most widely, followed by haematologic events and laboratory abnormalities. Reported infections per patient were lower under extracorporeal photopheresis (ECP) for aGvHD (0.267 infections per patient over 6 months) relative to any of the therapies studied (ranging from 0.853 infections per patient per 6 months under etanercept up to 1.998 infections per patient on inolimomab). Conclusion: The reported incidence of infectious AEs in aGvHD and grade 3–5 AEs in cGvHD was lower on ECP compared with pharmaceutical management.

scholarly journals Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Amr Nassar ◽  
Ghada Elgohary ◽  
Tusneem Elhassan ◽  
Zubeir Nurgat ◽  
Said Y. Mohamed ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Corticosteroid Treatment ◽  
Complete Response ◽  
Primary Treatment ◽  
Lower Grade ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Pooled Data

Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

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