Current and future approaches for control of graft-versus-host disease

Koreth, John; Antin, Joseph H.

doi:10.1586/17474086.1.1.111

Cited by 33 publications

(33 citation statements)

References 234 publications

(173 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most relevant risk factors are: the degree of donor-recipient human leukocyte antigen (HLA)-mismatches, donor and recipient age and sex as well as the stem cell source. Grade II-IV acute GvHD occur in approximately 35% of matched related alloSCT and in up to 50% of unrelated alloSCT (32) Despite numerous clinical studies, the standard immune suppressive regimens for prevention of acute GvHD have changed little in the last two decades. Standard prophylaxis typically involves improved HLA-matching of donor and recipient and consists of a short course of methotrexate (MTX) and cyclosporine (33).…”

Section: Msc In Regenerative Medicinementioning

confidence: 99%

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

Giebel

Kordelas²,

Börger

2017

Stem Cell Investig.

126

115

View full text Add to dashboard Cite

Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after hematopoietic stem cells as the second most investigated and applied somatic stem cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative activities. Against the initial assumption, MSCs may not primarily exert their therapeutic functions in a cellular but rather in a paracrine manner. Here, extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as major mediators of these paracrine effects. Meanwhile, MSC-EVs have been applied to an increasing amount of different animal models and were tested in a patient suffering from steroid-refractory acute graft-versus-host disease (acute GvHD) as well as in a patient cohort with chronic kidney disease. So far, the MSC-EV administration appears to be safe in humans and all tested animal models. Improvements were reported in all settings. Thus, MSC-EVs appear as promising novel therapeutic agents which might help to improve disease associated symptoms in millions of patients. Here, we review some of the milestones in the field, briefly discuss challenges and highlight clinical aspects of acute GvHD and its treatment with MSCs and MSC-EVs.

show abstract

Section: Msc In Regenerative Medicinementioning

confidence: 99%

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

Giebel

Kordelas²,

Börger

2017

Stem Cell Investig.

126

115

View full text Add to dashboard Cite

show abstract

“…It was reported to have response rate of 45 % [138]. A retrospective study of de novo and steroid-refractory cGVHD has shown response rates of 90 and 75 %, respectively [139].…”

Section: Mycophenolate Mofetil (Mmf)mentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

View full text Add to dashboard Cite

owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

show abstract

“…MMF is increasingly used in salvage therapy for refractory chronic GVHD and has a reported response rate of over 45% [10]. The largest study in the chronic GVHD setting [11] reported retrospectively on the use of MMF for de novo (n = 10) or refractory (n = 24) chronic GVHD.…”

Section: Pharmacological Compoundsmentioning

confidence: 99%

“…The mode of action of ECP in GVHD remains poorly understood and may be of a multifactorial nature. Proposed mechanisms involve the alteration of host antigen presentation, effector lymphocyte apoptosis and enhancement of donor-derived Treg cells [10]. …”

Section: Nonpharmacological Therapiesmentioning

confidence: 99%

Novel Immunosuppression Compounds and Experimental Therapies for Chronic Graft-Versus-Host Disease

Michael

Shimoni

Nagler³

2013

Acta Haematol

View full text Add to dashboard Cite

Chronic graft-versus-host disease (GVHD) is a severe complication of allogeneic stem cell transplantation, with a substantial impact on the quality of life and survival, still lacking with regard to an optimal therapeutic strategy. Corticosteroids are considered the standard of care for first-line treatment of chronic GVHD, but only a minority of the patients responds to them durably. Management of steroid-refractory chronic GVHD is not well defined. This review surveys novel treatment strategies, such as therapies that expand regulatory T cells, target B cells or target the processes implicated in fibrosis that may allow more effective control of chronic GVHD in the future. Most therapies are based solely on phase II trials or on retrospective analyses with a wide range of overall responses. Large, well-designed prospective studies are eagerly needed to establish better treatments, as well as valid biomarkers to identify the likelihood of the response to a drug in advance.

show abstract

Current and future approaches for control of graft-versus-host disease

Cited by 33 publications

References 234 publications

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

State-of-the-art acute and chronic GVHD treatment

Novel Immunosuppression Compounds and Experimental Therapies for Chronic Graft-Versus-Host Disease

Contact Info

Product

Resources

About