Steroids Versus Steroids Plus Additional Agent in Frontline Treatment of Acute Graft-versus-Host Disease: A Systematic Review and Meta-Analysis of Randomized Trials

Rashidi, Armin; DiPersio, John F.; Sandmaier, Brenda M.; Colditz, Graham A.; Weisdorf, Daniel J.

doi:10.1016/j.bbmt.2016.02.021

Cited by 33 publications

(20 citation statements)

References 30 publications

(39 reference statements)

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“…Corticosteroids are the standard first-line agent, particularly methylprednisolone at an initial dose of 2 mg/kg/day intravenously [ 82 ]. Rashidi et al carried out a systematic review and meta-analysis of randomized trials and concluded that standard treatment is better in terms of overall survival and response rates when compared with higher doses of systemic steroids or combined regimens of steroids and antithymocyte globulin (ATG), infliximab, an anti-IL-2 receptor antibody (daclizumab and BT563), a CD-5-specific immunotoxin, or mycophenolate mofetil [ 87 ]. An initial dose of 1 mg/kg/day for less severe forms (grade II GVHD) is associated with decreased toxicity without compromising therapy response or mortality rates, and should therefore be attempted [ 88 ].…”

Section: Treatmentmentioning

confidence: 99%

Cutaneous Graft-Versus-Host Disease: Diagnosis and Treatment

et al. 2017

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Graft-versus-host disease (GVHD) is an immunological reaction and a frequent complication following allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and may have a significant negative impact on the patient’s quality of life, particularly in the chronic-stage setting. Many different organs can be involved, which leads to a wide range of clinical manifestations. In this context, dermatologists play a key role by diagnosing and treating GVHD from the outset since cutaneous features are not just the most common but are also usually the presenting sign. Several skin-direct therapies are available and may be indicated as monotherapy or adjuvant treatment in order to allow faster tapering and withdrawal of systemic immunosuppression. Treatment of steroid-refractory patients remains a challenge and, to date, no consensus has been reached for one single agent in second-line therapy. This article aims to review skin involvement as well as provide and update discussion on therapeutic options for both acute and chronic cutaneous GVHD.

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Section: Treatmentmentioning

confidence: 99%

Cutaneous Graft-Versus-Host Disease: Diagnosis and Treatment

et al. 2017

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“…1,2 Classically, three stages are involved in the development of aGVHD: firstly, tissue damage from conditioning regimen mediates the activation of antigen-presenting cells (APCs); secondly, donor T lymphocytes are then activated by recipient antigens presented by host APCs; thirdly, donor T lymphocytes attack targets tissues and cause damage. However, graft-versus-host disease (GVHD) frequently happens after allo-HSCT such that fatal GVHD offsets the benefit of allo-HSCT and hampers development of this treatment.…”

Section: Backg Rou N Dmentioning

confidence: 99%

Enhanced alleviation of aGVHD by TGF‐β1‐modified mesenchymal stem cells in mice through shifting MΦ into M2 phenotype and promoting the differentiation of Treg cells

Liu

Deng

et al. 2019

J Cellular Molecular Medi

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Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative method in treating haematologic malignant diseases. Graft-versus-host disease (GVHD) is a common complication post-allo-HSCT, which can be life-threatening.Mesenchymal stem cells (MSCs) as an adult stem cell with immunoregulatory function have demonstrated efficacy in steroid resistant acute GVHD (aGVHD). However, the outcome of aGVHD treated with MSCs in clinical trials varied and its underlying mechanism is still unclear. TGF-β1 is a potent cytokine, which plays a key role in immunoregulation. In the present study, we firstly transduced the lentivirus vector containing TGF-β1 gene with mouse bone marrow-derived MSCs. Then, we investigated the immunosuppressive effect of TGF-β1 gene-modified MSCs on lymphocytes in vitro and its preventive and therapeutical effects on murine aGVHD model in vivo.Murine MSC was successfully isolated and identified. TGF-β1 was efficiently transduced into mouse MSCs, and high level TGF-β1 was detected. MSC-TGF-β1 shared the same morphology and immunotypic features of normal MSC. In vitro, MSC-TGF-β1 showed enhanced immunosuppressive function on lymphocyte proliferation.In vivo, MSC-TGF-β1 showed enhanced amelioration on the severity of aGVHD both in prophylactic and therapeutic murine models. Finally, the macrophages (MØs) derived from MSC-TGF-β1-treated mice showed a remarkably increasing of anti-inflammatory M2-like phenotype. Furthermore, the differentiation of CD4+ CD25+ Foxp3+Treg cells was significantly increased in MSC-TGF-β1-treated group. Taken together, we proved that MSC-TGF-β1 showed enhanced alleviation of aGVHD severity in mice by skewing macrophages into a M2 like phenotype or increasing the proportion of Treg cells, which opens a new frontier in the treatment of aGVHD. K E Y W O R D Sallogeneic haematopoietic stem cell transplantation, graft-versus-host disease, mesenchymal stem cell, transforming growth factor-β1 | 1685 WU et al.

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“…Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation [1]. High-dose steroids are the mainstay of frontline therapy for aGVHD, and the addition of other agents in this setting has not improved outcomes [2,3]. Steroid-refractory aGVHD has a dismal prognosis, and most patients succumb to organ failure or infection after a few months [4À6].…”

Section: Introductionmentioning

confidence: 99%

Outcomes and Predictors of Response in Steroid-Refractory Acute Graft-versus-Host Disease

Rashidi

DeFor

Holtan

et al. 2019

Biology of Blood and Marrow Transplantation

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The prognosis of steroid-refractory acute graft-versus-host disease (aGVHD) is poor, and predictors of response and survival are unclear. In an exploratory analysis of 203 steroid-refractory aGVHD patients with prospectively collected GVHD data who received antithymocyte globulin, etanercept, or mycophenolate mofetil (MMF) as second-line treatment, we determined the predictors of day 28 response, 2-year overall survival, and 2-year nonrelapse mortality (NRM). To minimize the risk of finding false-positive results, we used least absolute shrinkage and selection operator regression, aggressively eliminating variables that are unlikely to be associated with outcome. Day 28 response to second-line therapy was 38% (complete response, 23%), with a 2-year overall survival of 25% and a 2-year NRM of 62%. Factors associated with response were GVHD prophylaxis, organ involvement, and initial aGVHD to steroid-refractory aGVHD interval. Specifically, compared with cyclosporine/MMF as GVHD prophylaxis, the odds ratio (OR) for calcineurin inhibitor/methotrexate was .8 and for cyclosporine/prednisone .6. The OR for aGVHD to steroid-refractory aGVHD interval 14 versus <14 days was 1.3. The ORs for skin only involvement and gut or liver only involvement when compared with multiorgan involvement were 1.4 and 1.2, respectively. The only variable associated with worse survival was age, with a hazard ratio (HR) per decade of 1.04 for overall mortality. Similarly, age was the only variable associated with NRM (HR per decade, 1.02). When compared with complete response, no response at day 28 increased the risk of death (HR, 2.4; 95% confidence interval, 1.5 to 3.7). In conclusion, by means of an underused statistical technique in the field of transplantation, we identified predictors of response and survival in steroid-refractory aGVHD. Our results highlight the importance of developing novel treatment strategies because current treatments yield poor outcomes.

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Steroids Versus Steroids Plus Additional Agent in Frontline Treatment of Acute Graft-versus-Host Disease: A Systematic Review and Meta-Analysis of Randomized Trials

Cited by 33 publications

References 30 publications

Cutaneous Graft-Versus-Host Disease: Diagnosis and Treatment

Cutaneous Graft-Versus-Host Disease: Diagnosis and Treatment

Enhanced alleviation of aGVHD by TGF‐β1‐modified mesenchymal stem cells in mice through shifting MΦ into M2 phenotype and promoting the differentiation of Treg cells

Outcomes and Predictors of Response in Steroid-Refractory Acute Graft-versus-Host Disease

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