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Nk Cells Of Donor Alloreactive And Correlation Of Gvhd & The Gvl And In Cr1 Al Autologous And Allogeneic Hematopoietic Stem Cell Transplantation Efficacy Comparison

Posted on:2005-08-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:H H WangFull Text:PDF
GTID:1114360185973259Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective The strategy of preventing graft-versus-host disease (GVHD) and concomitantly amplifying graft-versus-leukemia (GVL) effects can enhance the efficacy and safety of allogeneic hematopoietic stem cell transplants (allo-HSCT). A recently published study demonstrated that KIR ligand incompatibility in the graft-versus-host (GVH) direction was associated with better outcomes in haplo-identical, T-cell-depleted HSCT from a relative. Alloreative NK cells not only can eliminate residual leukemic cells, but also prevent the development of acute GVHD. This present study included three aspects as follows. Firstly, investigating the expression of NK cells HLA-I-specific inhibitory receptors in healthy donors and patients with leukemia. Secondly, examining the reconstitution of NK cells receptor repertoire and the cytotoxicity of reconstituted NK cells. Finally, exploring the role of donor-versus-recipient NK cell alloreactivity on GVHD and GVL effects. Methods Flow cytometry analyzes the expression of NK cell HLA class- I -specific inhibitory receptors in peripheral blood (PB) of donors and patients and in vitro cultured NK cells. NK cell cytotoxicity was measured by a standard 4-hour 51Cr release assay. Using PCR- sequence-specific primer analysis of DNA determines HLA type. In clinical full haplo-identical family HSCT, donor granulocyte colony-stimulating factor (G-CSF)-mobilized PB stem cells was used as a source of hematopoietic stem cells (HSCs) in 11 patients, and G-CSF-mobilized bone marrow stem cells were transplanted in 2 cases. Conditioning regimen mainly consisted of total-body irradiation (TBI) follwed by cyclophosphomide and cytosine arabinoside. Cyclosporin or FK506, short-term methotrexate and anti-CD25 monoclonal antibody was given for GVHD prophylaxis. Some patients also received mycophenolate...
Keywords/Search Tags:natural kill cell, alloreactivity, receptor, hematopoietic stem cell transplantation, HLA, haplotype, Leukemia, first complete remission, Hematopoietic stem cell transplantation, autologous, allogeneic
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