Search

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen., Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT., Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group., Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Su, Wang, Li, Li, Jing, Xu, Wang, Zheng, Gao, Hu, Gao and Liu.)

Aim: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury., Methods: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of sham-operation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histological alterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously., Results: Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150'groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60'R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60'R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047)., Conclusion: Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.

Objective: To explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and investigate the roles of leptin and orexin-A in acute inflammatory responses., Methods: An intestinal I/R injury rat model was established, and the rats were grouped according to duration of the reperfusion time following a 60-min ischemia. Radioimmunoassay was used to examine the protein levels of leptin in the serum and adipose tissue, and the protein levels of orexin-A in the plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was also performed to detect the mRNA expressions of adipose leptin and hypothalamus orexin-A., Results: Compared with that before injury, serum leptin level of 60-min ischemia with 30-min reperfusion (I60'R30') group decreased significantly and that of I60'R360' increased significantly. Compared with the sham-operation group (sham) after injury, serum leptin level of I60'R360' group increased significantly, and adipose leptin protein levels of I60'R30' and I60'R90' groups decreased significantly, whereas that of I60'R360' group increased obviously. Compared with sham group after injury, adipose leptin mRNA expressions of I60'R30', I60'R240' and I60'R360' groups all increased significantly, while that of I60'R150' showed significant decrease. No significant changes were noted in the protein levels of orexin-A either in the plasma or hypothalamus after I/R injury. In comparison with sham group after injury, hypothalamus orexin-A mRNA expressions of I60'R30' and I60'R90' groups showed gradual but significant decrease, and till 150 min of reperfusion, the expression reached its lowest, followed then by slow recovery at 240 and 360 min, though still remaining significantly lower than that of sham group., Conclusion: Leptin and orexin-A have a time-dependent response to intestinal I/R injury, but the former appears to exhibit a faster response, and they may play a certain role in the metabolic disorders of acute inflammation.