scholarly journals First- and Second-Line Systemic Treatment of Acute Graft-versus-Host Disease: Recommendations of the American Society of Blood and Marrow Transplantation

2012 ◽  
Vol 18 (8) ◽  
pp. 1150-1163 ◽  
Author(s):  
Paul J. Martin ◽  
J. Douglas Rizzo ◽  
John R. Wingard ◽  
Karen Ballen ◽  
Peter T. Curtin ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Systemic Treatment ◽  
Second Line ◽  
Host Disease ◽  
Graft Versus Host ◽  
Blood And Marrow Transplantation ◽  
American Society ◽  
Acute Graft

Deleterious Roles of the KIR Ligand Mismatch on Acute Graft Versus Host Disease in Unmanipulated HLA-Mismatched/Haploidentical Blood and Marrow Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2874-2874
Author(s):  
Xiao Jun Huang ◽  
Xiang Yu Zhao ◽  
Dai Hong Liu ◽  
Kai Yan Liu ◽  
Lan Ping Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Multivariate Analysis ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Blood And Marrow Transplantation ◽  
Acute Graft

Abstract The beneficial effect of KIR ligand mismatch with a very low incidence of rejection, acute graft versus host disease (aGVHD), and leukemia relapse had been demonstrated by Perugia’s group in the Haploidentical mismatched Hematopoitic cell transplantation (HCT) with extensive T cells depletion in vitro. However, many analytical results of the haploidentical and unrelated mismatched transplantation appeared to be inconsistent with Perugia’s work. The disputes in the inconsistent roles of KIR ligand mismatch seem to be caused by the different transplant protocols with different extent of T cells depletion in vitro or in vivo. In recent years, we successfully established a novel protocol—conditioning including antithymocyte globulin followed by un-manipulated HLA-mismatched/haploidentical blood and marrow transplantation, which can achieve comparable outcomes to HLA-identical sibling transplantation. Following the contradictory results about the KIR ligand mismatch in the haploidentical related and mismatched unrelated HCT, we have evaluated the roles of the KIR ligand mismatch in 94 leukemia patients undergoing unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation. Multivariate analysis showed that both KIR ligand mismatch (HR 2.833, CI, 1.286–6.241, p=0.01) and doses of T cells (HR 3.059, CI, 1.292–7.246, p=0.011) were independent risk factors causing the acute graft versus host disease (aGVHD). In addition, compared to patients without KIR ligand mismatch, KIR ligand mismatch worsened the adverse effect of ‘high’ dose T cells (>1.48×108/kg) on aGVHD (100% vs 63.3%, p=0.036), and increased the incidence of aGVHD in patients with HLA-C mismatch (80% vs 57.4, p=0.056). Since multivariate analysis demonstrated that high risk leukemia is the only predictor for TRM, relapse and OS, we further analyzed the effect of KIR ligand mismatch on prognosis in standard and high risk patients. The differences in TRM (50% vs 7.6%, p=0.005) and OS (50% vs 88.4%, p=0.014) between patients with and without KIR ligand mismatch were most striking for standard risk. Therefore we conclude that due to the presence of large dose T cells in the allograft, the alloreactivity of NK cells had been inhibited and KIR ligand mismatch directed alloreactive T cells played crucial roles in our model.

The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2754-2759 ◽  
Author(s):  
Geoffrey R. Hill ◽  
James L. M. Ferrara
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Gi Tract ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT), limits the application of this curative but toxic therapy. Studies of inflammatory pathways involved in GVHD in animals have shown that the gastrointestinal (GI) tract plays a major role in the amplification of systemic disease. Damage to the GI tract increases the translocation of inflammatory stimuli such as endotoxin, which promotes further inflammation and additional GI tract damage. The GI tract is therefore critical to the propagation of the “cytokine storm” characteristic of acute GVHD. Experimental approaches to the prevention of GVHD include reducing the damage to the GI tract by fortification of the GI mucosal barrier through novel “cytokine shields” such as IL-11 or keratinocyte growth factor. Such strategies have reduced GVHD while preserving a graft-versus-leukemia effect in animal models, and they now deserve formal testing in carefully designed clinical trials.

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