| Human cytomegalovirus, of the β-herpesviridae family, present in approximately 90 % of the population of Chinese. CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells. After infection the virus cannot be completely eliminated, latent in certain CD34+ hematopoietic progenitor cells, when the cell differentiated, the virus can be preserved. When the patients were immunocompromised, the latent virus can be actived again.Allogeneic hematopoietic stem cell transplantation for treatment of hematological alignancies has been widely used at present, but infections remain the major complications after hematopoietic stem cell transplantation. Cytomegalovirus is one of the common source of opportunistic infections after hematopoietic stem cell transplantation. Multivariate model identified myeloablative preparative regimen and acute graft-versus-host disease prior to infection as risk factors for first CMV infection. Multivariate analysis identified the diagnosis of lymphoma/myeloma and GVHD as risk factors for subsequent CMV infection. Some research analysised the risk factors for progression from cytomegalovirus viremia to cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation, and identified several risk factors for progression to CMV disease, including high initial viral load,leukopenia, and neutropenia at the time of detection of CMV viremia. On multivariate analysis, leukopenia remained an independent predictor. This indicates that leukopenia initially documented with CMV viremia is related to lower viral response to preemptive therapy and is a notable risk factor for progression from CMV viremia to CMV disease.Despite the efficiency of pharmacotherapy with ganciclovir and foscarnet, the use of pharmacotherapy also cause myelosuppression and renal toxicity. Antiviral drugs can lead to late-onset disease, that may be worse than the original reactivation, because of the use of the pharmacotherapy can delay virus-specific immune recovery.The controlling of the virus depends on the virus-specific cytotoxic T lymphocytes, and adoptive transfer virus-specific cytotoxic T lymphocytes may be one of the most attractive and innovative approaches. Several other groups begin to develop different method to generate the virus-specific cytotoxic T lymphocytes. The approaches to generate the CTL are the classic ex vivo expansion, the use of multimers to select the CTL, and the gamma-capture technique to isolate the CTL. In the ex vivo expansion, there are the virus lysate, peptide, protein of virus, and nucleofection of APC as the source of antigen to generate the CTL. The period of ex vivo culture have been shortened with the use of cytokine combinations to expand virus specific T cells. The tetramers selection, in which the active T cell are selected using magnetically labeled peptide tetramers, is limited by the restriction of HLA alleles and the large volume of blood needed. The gamma-capture, in which T cell stimulated by APCs expressing virus antigen to product IFN-γ are selected, is not restricted to certain HLA types, but still need large volume of donor blood.We aimed to analysis the incidence of cytomegalovirus infection and related risk factors after allogeneic hematopoietic cell transplantation and to develop a rational strategy for the preemptive treatment of CMV infection. The clinical data involving 398 patients undergoing allogeneic hematopoietic cell transplantation from December 2011 to December 2014 were analyzed retrospectively using a Kaplan Meier analysis and Logistics model. We found that 233 of the 398 patients had developed post-transplant CMV reactivation(58.5%). Among all tested factors, we found the following risk factors in univariate analysis to be associated with first CMV infection: HLA mismatch, ATG administration, acute graft versus host disease(aGVHD), the use of prednisone≥1 mg/kg body weight or equivalent. In multivariate analysis, HLA mismatch(HR=2.765, p=0.000), ATG administration(HR=3.866, p=0.000), using prednisone≥1 mg/kg body weight or equivalent(HR=4.767, p=0.000) maintained significance. In conclusion, HLA mismatch, ATG administration, using prednisone≥1 mg/kg were risk factors for first CMV infection.We aimed to generate CMV-specific T cell isolated from G-CSF mobilized hemopoietin progenitor cell products. Monocyte-derived dendritic cells were enriched by adherence, which pulsed with CMV peptides. The mo-DC were used to stimulate donor T cells at an effector–tostimulator ratio of 10:1. By analyzing the cell phenotype,IFN-γ gamma detection in cells, cytokine secretion to identify the biological characteristics of cells of generated cells. It is concluded that the number of cultivated lymphocytes increased, the proportion of CD3 cells increased obviously, and secretion of IFN- gamma inside the cells was detected.Compared with negative control group, cytokine secretion increased significantly. The above all demonstrated the specific cell killing activity of cell-products from this manufacturing method.The experiment involved 6 post-transplant CMV infection patients(enrolled from Apr. 2015 through Mar. 2016) who were treated with our manufactured cells with the plan of a single dose of 2×107cells/m2 once a week till negative CMV or inefficiency after 4 consecutive injections. The inspection of CMV was with Q-PCR twice a week. The analyzed result showed efficiency and no adverse event in the control of CMV infection.In conclusion, HLA mismatch, ATG administration, using prednisone≥1 mg/kg are risk factors for first CMV infection. G-CSF mobilized hemopoietin progenitor cell products can successfully be used to isolate antigen-specific T cells, widening the accessibility of this therapy in the unrelated donor setting. Adoptively transfusion donor-derived cytomegalovirus specific cytotoxic T lymphocytes did not increase in acute or chronic graft-versus-host disease attributable to CTL infusion. |
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