The treatment of Epstein-Barr virus (EBV)associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable chall...
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The treatment of Epstein-Barr virus (EBV)associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD, These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.
A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal ...
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A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection (abbreviated as 5.5 Gy x 2 + PY + IV). AII recipients survived more than 1 year after this treatment (more than 64 weeks after birth), Abnormal T cells (Thy1.2(+)/B220(+)/CD3(+)/CD4(-)/CD8(-)) present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells, The treated mice are free from autoimmune diseases, Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved among T cells, B cells, and antigen-presenting cells (APCs) of the treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses. Newly developed T cells are tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex (MHC) determinants. These findings clearly indicate that severe autoimmune diseases in MRL/lpr mice are completely ameliorated by the treatment without recourse to immunosuppressants, and that the treated MRL/ lpr mice show normal immune functions, strongly suggesting that this strategy would be applicable to humans. (C) 2000 by The American Society of Hematology.
To evaluate the response rate and potential toxicities, a phase II trial was conducted of fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated low grade and select intermediat...
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To evaluate the response rate and potential toxicities, a phase II trial was conducted of fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated low grade and select intermediate grade lymphoid malignancies. Symptomatic patients with preserved end organ fu notion received cyclophosphamide 600 mg/m(2) intravenous (iv) day 1 and fludarabine 20 mg/m(2) iv days1 through 5, followed by filgrastim 5 mu g/kg subcutaneous starting approximately day 8. Treatment was repeated every 28 days until maximum response or a maximum of 6 cycles. Sixty patients, median age 53.5 years, were enrolled. Thirty-seven patients with non-Hodgkin lymphoma (NHL) were stage IV and 6 were stage ill, Eleven of 17 patients with chronic lymphocytic leukemia (CLL) were Rai intermediate risk end 6 were high risk. The overall complete response (CR) rate was 51% and the partial response (PR) rate was 41%. Of patients with CLL, 47% achieved a CR and the remaining 53% achieved a PR. Of patients with follicular lymphoma, 60% achieved CR and 32% achieved a PR. Although the toxicity of this regimen was mainly hematologic, significant nonhematologic toxicities, including infections, were seen. Twenty-four patients subsequently received an autologous or allogeneic stem cell transplant. Engraftment was rapid, and there were no noticeable procedure toxicities in the immediate posttransplant period attributable to the fludarabine and cyclophosphamide regimen. Fludarabine, cyclophosphamide, and filgrastim make up a highly active and well-tolerated regimen in CLL and NHL. (Blood. 2000;96:71-75) (C) 2000 by The American Society of Hematology.
Immunochemical and serologic studies of cold agglutinins in patients with chronic cold agglutinin disease (CCAD) showed the almost exclusive occurrence of Ig[immunoglobulin]M .kappa. antibodies with specificity for th...
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Immunochemical and serologic studies of cold agglutinins in patients with chronic cold agglutinin disease (CCAD) showed the almost exclusive occurrence of Ig[immunoglobulin]M .kappa. antibodies with specificity for the I antigen of red cells. An unusual subgroup of patients was delineated in which the cryoprotein is IgM .lambda., frequently lacks I specificity and often cryoprecipitates. Studies of such a protein from a patient with an unusual array of immunoproliferative disorders including Grave''s disease with exophthalmos and Waldenstrom''s macroglobulinemia indicate that the cryoprecipitating and cold agglutinating properties probably derive from the same protein. The occurrence of this type of antibody should suggest the presence of a more aggressive lymphoproliferative disorder than simple CCAD.
Rosai-Dorfman病(窦组织细胞增生伴巨大淋巴结病,Sinus histiocytosis with massive lymphadenopathy,SHML)是一种良性的淋巴组织增生性疾病,临床上属罕见病,易漏诊和误诊。现将我院诊断和治疗的5例Rosai-Dorfman病患者作如下分析。[第...
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Rosai-Dorfman病(窦组织细胞增生伴巨大淋巴结病,Sinus histiocytosis with massive lymphadenopathy,SHML)是一种良性的淋巴组织增生性疾病,临床上属罕见病,易漏诊和误诊。现将我院诊断和治疗的5例Rosai-Dorfman病患者作如下分析。[第一段]
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