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

Abstract

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.

IL‐27p28 is essential for parent‐to‐F1 acute graft‐versus‐host disease

“…There is a persistent effort to employ immune‐therapy in GVHD. However the treatments that have been tried in the clinic have had limited success as attested by the remaining mortality rates. Our observation suggests that IL‐27 could be a novel target for GVHD prevention.…”

Total Body Irradiation and Risk of Diabetes Mellitus; A Meta-Analysis

“…First, for age group, we categorized the studies to include only pediatric population and the other for adult patients. Pooled MD among adult group (Baker et al, 2007;Armenian et al, 2012) was 2.09, 95% CI 0.95-4.61, I 2 =71.7% while for the pediatric group (Taskinen et al, 2000;Hoffmeister et al, 2004;Neville et al, 2006;Oudin et al, 2011;Michael et al, 2013;Hirabayashi et al, 2014;Oudin et al, 2015;Nakagawa et al, 2018;Shalitin et al, 2018), the pooled MD was 8.43, 95% CI 5.51-12.91, cross-sectional study design has limitations to accurately diagnose DM/IGM after patients received TBI as the diagnosis is based on a single timeframe rather than a prolonged period of follow-up time in cohort studies. The association remained statistically significant after exclusion of two cross-sectional studies.…”

“…(Hilgendorf et al, 2015) Previous studies had mentioned the possibilities of developing hypertension, dyslipidemia as well as endocrinologic abnormalities with various risk factors (Baker et al, 2007;Hoffmeister et al, 2010;Wei et al, 2016;Bielorai et al, 2017). Not to mention known co-morbidities from the treatment itself such as graft versus host disease (GVHD) (Socie and Ritz, 2014;Arora et al, 2016) or infectious complications (Nakano et al, 2014;Kumar et al, 2015) which are well known to associate with the immunocompromised state rendered by the treatments (Michael et al, 2013).…”

Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation

“…The GVHD-process is swamped with positive feedback loops which amplify the reactions further and explain why aGVHD is so hard to treat. Current standard therapy for development of GVHD is high-dose corticosteroids, but it is not always successful (138). Of course, the best would be to prevent development of GVHD which is why patients receive prophylactic treatment, described in section 1.3.2.5.…”