| Objective:1To establish a stable model of acute graft-versus-host disease (aGVHD) after murine allogeneic bone marrow transplantation (allo-BMT).2Infusion of the donor bone marrow mesenchymal stem cells (MSCs) into recipient mice, explore the role of bone marrow MSCs in the prevention of aGVHD after allo-BMT.Methods:Established murine allo-BMT model of C57BL/6(H-2b)â†'BALB/c (H-2d). The major histocompatibility antigen (MHC) of the donor and recipient mice was completely mismatched. The recipient mice were randomly divided into six groups:the first group was the control group (the B+S group), who did not receive donor bone marrow MSCs during transplantation; the second, third and forth group were the experiment groups, who received different doses of donor bone marrow MSCs during different times of transplantation, the d0group received5×105donor bone marrow MSCs in the day of transplantation, the d2-1group and the d2-5group received1×105,5×105donor bone marrow MSCs in2days after transplantation respectively; the fifth group was no-transplantation group (the PBS group), who only received irradiation group; the sixth group only received donor bone marrow cells (the BM group). The aGVHD after bone marrow transplantation and survival time of recipient were observed in each group. T lymphocyte subsets and implantation rate in peripheral blood of each group were detected by flow cytommeter after bone marrow transplantation. The serum levels of Thl-type cytokine such as IL-2and Th2-type cytokine such as IL-4of each group were detected by ELISA after bone marrow transplantation.Results:1The recipient mice were injected with4×106donor bone marrow cells plus7×10splenocytes by caudal veins within about4-6hours after received8.5Gy total body irradiation (TBI) of137Cs, and began to appear typical aGVHD clinical manifesta-tions in about2weeks after transplantation. 2The mean survival time of control group (the B+S group) was (22.25±4.18) d. In three experiment groups:the mean survival time of the d0group was (19.73±2.61) d; the mean survival time of the d2-1group was (26.44±3.47) d; the mean survival time of the d2-5group was (27.62±5.28) d. The survival time of the mice in the d2-5group was significantly longer than the B+S group, there was a significant statistical difference between the two groups (P=0.006).3The clinical score of GVHD in the d2-5group and the d2-1group was always lower than the B+S group. In the16th day after transplantation, there was a significant difference in the clinical score of GVHD between the d2-1group and the B+S group (1.89±0.33VS2.57±0.79, P=0.037), and there was a significant difference in the clinical score of GVHD between the d2-5group and the B+S group (1.92±0.28VS2.57±0.79, P=0.017); In the20th day after transplantation, there was a significant difference in the clinical score of GVHD between the d2-1group and the B+S group (3.78±0.83VS5.43±0.78, P=0.006); In the27th day after transplantation, there was a significant difference in the clinical score of GVHD between the d2-5group and the B+S group (7.00±1.5VS8.50±0.71, P=0.038).4Allogeneic H-2b positive cells were higher than95%in peripheral blood in each group after transplantation, allogeneic bone marrow cells implanted successfully.5After transplantation the percentage of CD3+CD4+T cell reduced and the percentage of CD3+CD8+T cell increased in peripheral blood in each group, resulting in the ratio of CD4+/CD8+inverted. In2weeks after transplantation, the percentage of CD3+CD4+T cell in peripheral blood of the d2-5group was lower than the B+S group, and the percentage of CD3+CD8+T cell was higher than the B+S group, the ratio of CD4+/CD8+inverted more obviously. But there was no significant statistical difference between the two groups (P=0.057).6After transplantation2weeks, the serum level of IL-2in the d2-5group was lower than the B+S group, and the serum level of IL-4was higher than the B+S group. But there were no significant statistical differences between the two groups at each time point.Conclusions:1Established a stable aGVHD model of murine allo-BMT from C57BL/6(H-2b)â†'BALB/C (H-2d) successfully.2Donor bone marrow MSCs infusion in2days after transplantation could alleviate GVHD symptoms and prolong the survival time of the recipient mice that occurred aGVHD. 3Donor bone marrow MSCs infusion in the day of transplantation did not prolong the survival time of the recipient mice that occurred aGVHD. Objective:1Observe the efficacy of autologous stem cell transplantation (auto-HSCT) for adult patients with acute lymphoblastic leukemia (ALL) retrospectively.2Explore the related prognostic factors.Methods:A total of86adult ALL patients underwent auto-HSCT in transplant center of our hospital from November2001to January2012were followed up. Clinical characteristics and treatment outcomes of all patients were retrospectively analyzed. Survival and univariate prognosis was analyzed by the Kaplan-Meier method and multivariate analysis by COX regression model.Results:1Treatment outcomes were assessed in81adult ALL patients who underwent auto-HSCT, including of47standard-risk patients and34high-risk patients.21-,3-,5-, and10-year leukemia free survival (LFS) of standard-risk patients were (82.3±5.7)%,(76.9±6.5)%,(74.1±6.8)%,(67.4±8.9)%respectively, and relapse rate(RR) were (13.6±5.2)%,(21.6±6.4)%,(24.5±6.8)%,(31.3±9.0)%respectively.1-,3-,5-, and10-year leukemia free survival (LFS) of high-risk patients were (55.8±8.9)%,(39.8±9.3)%,(39.8±9.3)%,(39.8±9.3)%respectively, and relapse rate (RR) were (38.8±9.2)%,(56.4±10.0)%,(56.4±10.0)%,(56.4±10.0)%respectively.3T-ALL, white blood cell count(WBC) more than30×109/L when first visited, increased LDH, positive fusion gene of TCR and bone marrow transplantation were the adverse prognostic factors. Multivariate analysis showed bone marrow transplantation was an independent adverse prognostic factor.Conclusion:Auto-HSCT was a choice for adult ALL patients when suitable donors were unavailable. |
PDF Full Text Request