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Objective:To develop an ex vivo normothermic mechanical perfusion(NMP)and compare the effect of air-oxygenated NMP versus oxygen-oxygenated NMP on reducing renal injury from donor after cardiac death(DCD).Methods:All kidneys from DCD rats were subjected to 30 min in situ warm ischemia after cardiac attest.And harvested kidneys were stored for 8h under static cold preservation after NMP for 2h.In experimental groups, kidneys were subjected to either air-oxygenated NMP(group A, n=6)or oxygen-oxygenated NMP(group O, n=6). Sham operation(group C, n=6)and DCD kidneys under static cold preservation without NMP(group SCS, n=6)were employed as controls.The evaluation parameters included creatinine(Cr), aspartate amino transferase(AST)and lactate dehydrogenase(LDH)in perfusate, pathological changes by hematoxylin-eosin(HE)staining, histological criteria, expressions of myeloperoxidase and intercellular adhesion molecular-1(ICAM-1)by immunohistochemistry and Western blot, tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)by enzyme-linked immunoadsorbent assay and level of malondialdehyde(MDA)by thiobarbital method and activity of superoxide dismutase(SOD)by WST-8 in renal tissues.Differences between two groups were analyzed by two-tailed unpaired Student's test and differences among more than two groups by one-way ANOVA.Results:Renal arterial oxygen tensions in NMP perfusate were(576.3±68.2)mmHg with oxygen-oxygenation and(137.0±39.1)mmHg with air-oxygenation.There was significant difference( P<0.05). The pathological injury scores in groups SCS, O and A by HE staining were(7.0±0.1), (5.0±0.9)and(2.5±0.5); injury scores and the expressions of renal proximal tubular epithelial cell vacuolar degeneration in groups O and A were lower than those in group SCS( P<0.05)and injury score in group A was lower than group O( P<0.05). In perfusate, the levels of △Cr, △AST and △LDH in groups O and A were(43.9±52.8)μmol/L and(12.6±3.5)μmol/L, (532.3±52.8)U/L and(49.1±50.4)U/L and(9998.0±2014.4)U/L and(1477.0±810.4)U/L.There were significant differences( P<0.05). In perfused kidneys, the MDA level and SOD activity in groups O and A were(0.192±0.018)mmol/g, (0.162±0.023)mmol/g, (0.6±0.3)×10 3 U/g, (1.7±0.4)×10 3 U/g; TNF-α and IL-6 levels in groups O and A were(124.376±19.635)and(89.331±13.123)ng/g, and(4.038±1.026)×10 3 and(1.774±0.518)×10 3 ng/g.After air-oxygenated NMP, lower renal damage indices were characterized by a lower MDA level and a higher SOD activity, the lower levels of TNF-α and IL-6 and the lower expressions of MPO and ICAM-1 than those in oxygen-oxygenated NMP( P<0.05). Conclusions:NMP with air-oxygenation mimics renal perfusion under physiological conditions and decreases oxidative stress and inflammation injury.It may confer a better retrieval in DCD kidney against warm ischemia injury.
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BACKGROUND: Previous studies have shown that HLA-identical sibling allogeneic peripheral blood hematopoietic stemcelltransplantation (allo-HSCT) provides higher disease-free and overall survival rates for patients with intermediatecytogenetic risk acute myeloid leukemia (AML) in complete remission (CR). But prognosis factors have not been fullydefined.OBJECTIVE: To evaluate the outcome of patients with intermediate cytogenetic risk AML undergoing HLA-matchedallo-HSCT in CR, and to analyze the prognostic factors.METHODS: Fifty cases of intermediate cytogenetic risk AML in CR receiving HLA-matched allo-HSCT from January2009 to January 2015 were retrospectively analyzed. Primary outcome measures of the study included overall survival(OS), relapse rate and non-relapse mortality.RESULTS AND CONCLUSION: The 4-year OS of the study population reached to 64%, and the relapse rate and NRMreached to 18% and 20% respectively. Incidence of acute graft-versus-host disease was 26%. Different prognosis wasobserved between female donor/male recipient (FDMR) combination transplant and control (4-year OS: 50% vs. 71.9%,P=0.041), between patients requiring more than one course of induction chemotherapy to achieve CR and control(4-year OS: 40% vs. 70%, P=0.038), between older age (≥ 40 years) and control (4-year OS: 44.4% vs. 68.3%,P=0.056). The 4-year OS for matched sibling donor and matched unrelated donor was 63.2% and 66.7% (P=0.427),respectively. Further analysis revealed significantly high non-relapse mortality in FDMR combination transplant (P=0.024)and older age (≥ 40 years; P=0.043). Multivariate analysis revealed three negative prognostic factors: FDMRcombination (P=0.031, RR=1.38, 95% CI: 1.03-1.95), requiring more than one course of induction chemotherapy toachieve CR (P=0.016, RR=1.46, 95% CI: 1.10-1.98) and older age (≥ 40 years; P=0.024, RR=1.63, 95% CI: 1.32-2.12).To conclude, HLA-matched allo-HSCT is a choice for the intermediate cytogenetic risk AML case in CR. FDMRcombination, requiring more than one course of induction chemotherapy to achieve CR and older age (≥ 40 years) areconfirmed as risk factors of poor prognosis for HLA-matched allo-HSCT patients with intermediate cytogenetic risk AMLin CR. To these cases, the donor-recipient sex combination is more important than the donor type in donor selection.
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Objective To explore the expression of lymphoid-associated antigens in acute myloid leukemia and its clinical significance.Methods 84 patients with de nove (untreated) AML were classified by FAB classification and immunophenotype,of which 53 cases were analyzed by karyotype according to WHO standards.Patients were divided into 2 groups according to whether lymphoid antigen (Ly) was expressed or not.After all patients were treated with a standard remission-induction regimen for 1 course,bone marrow in 63 cases were re examined.Results 49 cases (58.3％) were classified into lymphoid surface antigen-positive acute myeloid leukemia (Ly+ AML) group,35 cases (42.7％) into lymphoid surface antigen-negative acute myeloid leukemia (Ly-AML) group.The incidences of hepatosplenomegaly and lymphadenopathy had significant differences between Ly+AML and Ly AML groups [55.1％ (27 cases) vs.22.9％ (8 cases),t=3.412,P=0.003].There were no significant differences in other indicators between the two groups.On the basis of equal intensity of chemotherapy,complete remission (CR) had no significant difference(x2 =1.995,P=0.158),the disease-free survival (DFS) in Ly + AML group was shorter than in Ly-AML group(t=2.427,P=0.019),the recurrence rate was higher in Ly + AML group than in Ly-AML group(x2 =4.132,P=0.044).Conclusions The expression of lymphoid associated antigens in acute myeloid leukemia is complex.Patients with Ly+AML show poor response to chemotherapy,and have poor prognosis.We should explore new chemotherapy for acute myeloid leukemia.