Diagnosis, Incidence and Treatment of Chronic Graft-Versus- Host Disease

After an allogeneic hematopoietic stem cell transplantation (SCT), theleading cause of non-relapse mortality and morbidity is the emergenceof the chronic graft-versus-host disease (cGvHD). Further, the incidenceof cGvHD has markedly dramatically increased by an increased use ofperipheral blood as a graft source. At the moment, over 50% of SCTrecipients have been shown to develop this multisystem inflammatorydisease, which happens late after the bone marrow transplantation. thepredominant and diagnostic organ pathologies that develop are usuallycutaneous and/or pulmonary despite the fact that cGvHD can affectalmost any target tissue. As for most diseases with fibrotic manifestations,unfortunately, no satisfactory therapy is available for the cGvHDcurrently. Standard primary treatment is glucocorticoids with or withoutother immunosuppressive agents. Nevertheless, almost nearly 50% ofpatients continue to have inadequate control of their cGvHD and requiresecond-line systemic treatment. Besides, systemic glucocorticoids arewrought with long term-complications and undesired issues, and hence,increasing morbidity and mortality in this patient population that areotherwise cured of their original malignancy.Our understanding of the pathophysiology of cGvHD has substantiallybeen advanced by the recent surge of preclinical and clinical studies.As a result, we now identify cGvHD as a complex immunologic processthat associate with multiple facets of adaptive and innate immunity suchas B cells, T cells, and macrophages and their interactions with the targettissue. Prominently, these studies have resulted in the recognition andclassification of targetable cellular and molecular mediators of cGvHD.Such findings might broaden our choice of potential new therapeutics tomanage these patients.Recent advances in the immunobiology of cGvHD provides a greatpossibility based on the strategically targeted therapeutics that grants uswith much more effective prevention and treatment options for controllingthe cGvHD. While a number of the newly identified targetable pathwaysare only in the conceptual stage, repurposing of existing reagents shouldallow the rapid assessment of efficacy in well-designed clinical trials.Such endeavor might hopefully build effective medical armamentariumsto be use alone or in combination with trivial toxicity and side effects,which should hopefully be truly steroid-sparing or steroid-free therapiesfor cGvHD. We review here the incidence of cGvHD in patients receivingallogeneic SCT, its causes and risk factors as well as available therapiesincluding those recently introduced in clinical trials phases.

کلیدواژه ها:

Graft-versus-host disease ، Clinical trials ، Allogeneic hematopoietic cell transplantation