An Experimental And Clinical Study On Graft-versus-Host-Disease

Objective:To analyze the difference of the rate of graft-versus-host disease (GVHD) between different condition regimens,stem sourses,prophylaxis of GVHD and the effect to prognosis; to research CD4+CD25+ T cells in the pathogenesis of acute (aGVHD) and chronic (cGVHD) GVHD ,and to observe the effect of anti-CD25 monoclonal antibody(mAb) in the prophylaxis and treatment of GVHD.Methods.From July 1996 to April 2003,fifty six patients received observation two to twenty five months long following allogeneic stem cell transplantation (AlloHSCT); Cyclosporine A (CsA) was replaced by anti-CD25 mAb because of renal toxicity in two patients,and in the other ten patients, anti-CD25 mAb was used to treat steroids-resistent GVHD.Twenty nine patients following AlloHSCT,nineteen idiopathic thrombocytopenic purpura (ITP) patients and thirteen normal people were sleeted,3 ~ 5mL fresh anti-coagulative peripheral blood were prepared,mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation,then washed ,stained with PE-anti-CD4 and FTTC-anti-CD25,and analyzed with flow cytometry.Results: ( 1 ) The effect of steroids is more poor in patients of II ~ IV aGVHD(P<0.05),and the prognosis of those refractory to steroids is more poor (P<0.05); (2) There is no significant difference (P>0.05) of the rate of aGVHD and cGVHD among nonmyeloablative peripheral blood stem cell transplantation (NST), unrelated and related bone marrow transplantation (R-BMT),although the rate of II ~ IV aGVHD is higher in the former (P>0.05),while the ratio of steroids-resistent aGVHD is significantly higher in patients of NST than that in those of R-BMT(P<0.05);(3) The creastine in the two patients became normal rapidly,but none of them was free from aGVHD.In the nine patients with aGVHD,two of them were complete response, four partial response,but to the patients of cGVHD,both of them were no response;(4)The rate of CD4+CD25+ T cells and the ratio of those cells in CD4+ T cells decreased significantly after the mobilization with G-CSF(P<0.05);(5)Compared to healthy volenteers,the rate and ratio in ITP patients of first diagnosis were lower(P<0.05),after effective treatment,the rate of CD4+CD25+ T cells increased significantly(P<0.05), otherwise, no significant variation (P>0.05); (6)There's no significant difference of the rate or the ratio among healthy volunteers, patients with or without aGVHD;(7)When compared to patients without cGVHD, the rate or the ratio were lower in those during the treatment of cGVHD (P<0.05),after effective treatment,significant variation were observed(P<0.05);the rate or the ratio was higher in healthy volunteers than that in those without cGVHD(P<0.05).Conclusion: (1) GVHD is one of the major facors that affected the prognosis of NST,prophylaxis in these patients and the treatment of steroids-resistent aGVHD need more attention ;(2) Probably, anti-CD25mAb can't be used to replace CsA in the prophylaxis of aGVHD,but some effect was found in the treatment of aGVHD,when it comes to cGVHD,much more evaluation was needed;(3)There's no relation between CD4+CD25+ T cells and the pathogenesis of aGVHD,but those cells might play a role in the pathophysiology of cGVHD.