The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon （1.6%-37.5%） and of these, the majority of patients will have widespread disease.1-7 Isolated...The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon （1.6%-37.5%） and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen. Resection of metastatic tumors of the pancreas has been reported, but its role in improving survival rates or quality of life is not clear.7,8 However,展开更多
There are two arms in the management of aplastic anemia,one allogeneic bone marrow transplantation(BMT) and the other immunomodulation therapy with antilymphocyte globulin(ALG).
Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leu...Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.展开更多
In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC...In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC) from BALB/c mouse (H-2 d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrovirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2 d×b) as one way mixed lymphocyte reaction (OWMLR). The cytotoxicity of treated BAC mouse SMNC against Na 2 51CrO 4 labeling SMNC from BALB/c mouse was observed. The bone marrow mononuclear cells (BMMNC) from BAC mouse treated by the above methods were transplanted into lethally-irradiated congenic BALB/c mice to observe the occurrence of GVHD. The results showed that the SMNC from BAC mouse after OWMLR with exogenous mFasL cDNA gene-transduced hematopoietic cells (HC) from BALB/c mouse in a ratio of 1 to 5 exhibited an obvious inhibition of the cytotoxicity against the BALB/c mouse spleen cells at different effector/target ratios as compared to the control group (P<0.01). The gradeⅠ GVHD or no GVHD and the 80 % survival rate at day 60 post-BMT were observed in the BALB/c mouse receiving BAC mouse BMMNC treated with similar way, while the grade Ⅱ-Ⅲ GVHD and the 20 % survival rate were noted in the control group (P<0.01). It is suggested that the attenuation of GVHD in allo-BMT recipient could be successfully achieved through FasL-Fas pathway in an H-2 haplotype disparate mouse combination.展开更多
Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effe...Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 on the reconstitution of T-cell immunity in allo-BMT mice Methods The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system T lymphocyte subset counts per spleen were analyzed by flow cytometry Lymphocyte proliferation response to ConA was examined to evaluate T-cell function CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation Results Gene engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 could express IL-2 and IL-3 (1300 ng·day -1 ·10 -6 cells and 1100 ng·day -1 ·10 -6 cells, respectively) under the control of doxycycline QXMSC1-IL-2+IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD4 + and CD8 + T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group ( P <0.01); make CD4 +/CD8 + ratio return to normal level at week 4; enhance splenocytes mitotic response to ConA ( P <0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice ( P <0.05) KH*2/5DConclusion The gene transduced stromal cell line QXMSC1-IL-2+IL-3 is able to accelerate T-cell immunity in allo-BMT mice展开更多
文摘The occurrence of metastatic lesions in the pancreas of patients with cancer, including hematological cancers,is uncommon （1.6%-37.5%） and of these, the majority of patients will have widespread disease.1-7 Isolated potentially resectable pancreatic metastases are rarely seen. Resection of metastatic tumors of the pancreas has been reported, but its role in improving survival rates or quality of life is not clear.7,8 However,
文摘There are two arms in the management of aplastic anemia,one allogeneic bone marrow transplantation(BMT) and the other immunomodulation therapy with antilymphocyte globulin(ALG).
文摘Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.
基金ThisprojectwassupportedbyagrantfromNationalNaturalSciencesFoundationofChina (No .39770 76 7)
文摘In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC) from BALB/c mouse (H-2 d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrovirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2 d×b) as one way mixed lymphocyte reaction (OWMLR). The cytotoxicity of treated BAC mouse SMNC against Na 2 51CrO 4 labeling SMNC from BALB/c mouse was observed. The bone marrow mononuclear cells (BMMNC) from BAC mouse treated by the above methods were transplanted into lethally-irradiated congenic BALB/c mice to observe the occurrence of GVHD. The results showed that the SMNC from BAC mouse after OWMLR with exogenous mFasL cDNA gene-transduced hematopoietic cells (HC) from BALB/c mouse in a ratio of 1 to 5 exhibited an obvious inhibition of the cytotoxicity against the BALB/c mouse spleen cells at different effector/target ratios as compared to the control group (P<0.01). The gradeⅠ GVHD or no GVHD and the 80 % survival rate at day 60 post-BMT were observed in the BALB/c mouse receiving BAC mouse BMMNC treated with similar way, while the grade Ⅱ-Ⅲ GVHD and the 20 % survival rate were noted in the control group (P<0.01). It is suggested that the attenuation of GVHD in allo-BMT recipient could be successfully achieved through FasL-Fas pathway in an H-2 haplotype disparate mouse combination.
基金ThisworkwassupportedbyagrantfromtheNationalNaturalScienceFoundation (No 3 0 170 895 )
文摘Background After T-cell depleted allogeneic bone marrow transplantation, impaired immune reconstitution is a major cause of morbidity and mortality in the recipient The purpose of this study was to observe the effects of the gene-engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 on the reconstitution of T-cell immunity in allo-BMT mice Methods The bone marrow stromal cell line QXMSC1 was co-transfected with IL-2 and IL-3 genes using a Tet-on gene expression system T lymphocyte subset counts per spleen were analyzed by flow cytometry Lymphocyte proliferation response to ConA was examined to evaluate T-cell function CDR3 spectratyping techniques were performed to evaluate TCR repertoire diversity at various time points post-transplantation Results Gene engineered bone marrow stromal cell line QXMSC1-IL-2+IL-3 could express IL-2 and IL-3 (1300 ng·day -1 ·10 -6 cells and 1100 ng·day -1 ·10 -6 cells, respectively) under the control of doxycycline QXMSC1-IL-2+IL-3 in combination with allogeneic bone marrow could significantly increase the counts of CD4 + and CD8 + T cell, 1.72 and 1.27-fold respectively at week 3 compared with TCD-BMT group ( P <0.01); make CD4 +/CD8 + ratio return to normal level at week 4; enhance splenocytes mitotic response to ConA ( P <0.01), and accelerate restoration of TCR repertoire diversity in the lethally irradiated mice ( P <0.05) KH*2/5DConclusion The gene transduced stromal cell line QXMSC1-IL-2+IL-3 is able to accelerate T-cell immunity in allo-BMT mice
