Treatment difficulty with acute GVHD – frequent cause of mortality after allogeneic hematopoietic stem cell transplantation

Abstract

Abstract:Objective: Acute graft-versus-host disease (aGvHD) remains a signifi cant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Methods: In this study, we have retrospectively evaluated the major risk factors for the development of aGvHD in 100 patients who underwent allogeneic transplantation at the University Hospital in Bratislava between January 2007 and December 2011. Results: 29 patients acquired acute GvHD (Grade I -12 patients, G II -5 , G III -3, G IV -9). We proved a higher incidence of developing aGvHD in patients with unrelated donor type, TBI conditioning and cyclosporine (CsA) replacement with mycophenolate mofetil due to CsA nephrotoxicity, while other risk factors such as older patient age, the use of peripheral blood progenitor cells and donor/recipient sex mismatch were without statistical significance. The average time of onset of aGvHD has been 57 days (range 13-260) after HSCT. Corticosteroids were used as standard initial therapy with 52 % complete response (CR) rate, althoug the likelihood of response rapidly decreased with increasing severity of disease (G IV -100 % refracterness). The response to primary therapy also correlated with overall survival. Patients with steroid-refractory aGvHD received a different second-line therapies (antithymocyte globulin, anti-TNFα antibody, anti CD52 antibody) with response rate 45 % (CR -18 %, PR -27 %). Conclusion: Outcome for the patients with steroid-refractory aGvHD was poor, disease very often returned or progressed with one year mortality rate 81 % , that represents an important therapeutic problem (Tab. 2, Ref. 10). Text in PDF www.elis.sk.

Vedolizumab in highly resistant acute gastrointestinal graft-versus-host disease after allogeneic stem cell transplantation: A single-center pediatric series

“…9,10 Graft-versushost disease prevention is based on pre-and post-transplantation pharmacological immunosuppression or graft engineering, such as T lymphocyte depletion. The GvHD first-line treatment consists of steroids and calcineurin inhibitors (CNIs), 11 but up to 50% of patients with aGvHD do not respond to this therapy. 12 In steroid-resistant (SR) aGvHD, multiple therapies have been studied, ranging from high-dose steroids to mono-and polyclonal antibodies (basiliximab, daclizumab, etanercept, anti-thymocyte globulin (ATG), infliximab), extracorporeal photopheresis (ECP), or cellular therapies with mesenchymal stem cells (MSCs).…”

Mucopolysaccharidosis enzyme production by bone marrow and dental pulp derived human mesenchymal stem cells

“…As neurological improvement correlates to the level of enzyme secretion [14,19] the higher level of enzyme production by MSCs has the potential to allow more widespread GAG clearance than HSC therapy. Together with the inherent properties of MSCs the results presented here suggest that they be investigated as a therapy for MPS disease either as a standalone approach or as an adjunct to HSC therapy to alleviate GvHD and improve GAG clearance [81,82].…”

“…In particular, their ability to form multiple cell types in vitro [20][21][22][23]26] and in vivo [77][78][79], their ability to cross the BBB [80], and their ability to inhibit T-cell proliferation and hence lower the immune response of the host [81,82] are pertinent to the treatment of MPS disease. In this study we have shown that MSCs produce and secrete multiple different MPS enzymes, they are readily transducible, transduction is stable with cell division and does not inhibit their ability to differentiate down multiple lineages in vitro.…”

Graft-versus-host disease management

“…Steroids and calcineurin inhibitor (CI) remain the gold standard for initial treatment of aGVHD (15). Mild skin aGVHD (grade I) can be treated with topical steroids alone.…”