Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment. 相似文献
Background: The level of the systemic inflammatory marker C-reactive protein (CRP) is elevated in many patients with malignant disease and may be related to nutritional status.
Objective: To analyze the association between serum CRP levels in patients with malignant tumors and their nutritional status.
Method: A total of 3,692 cases were analyzed and the serum CRP levels were determined using an immunometric assay. Nutritional status was assessed by using patient-generated subjective global assessment (PG-SGA). The biochemical evaluation of prealbumin (PA), albumin (ALB), cholesterol (CHOL), and triglycerides (TG) were assayed within 48?h admission to the hospital. The association between serum CRP concentration and the nutritional status, the stage of the tumor and other factors was analyzed by univariate and multivariate logistic regression analysis.
Result: Elevated serum CRP was observed in 47.6% (1,548/3,269) of patients compared with the reference value, and the median CRP concentration was 18.29?mg/l. Patient serum CRP concentrations in the malnourished group (PG-SGA B?+?C) were higher than in the well-nourished (PG-SGA A) patients (P?<?0.05). The serum CRP level was related to the patients' age, gender, tumor stage, and was affected by hepatitis, liver cirrhosis, diabetes, but it has no effect on hypertension. The CRP high patients had lower PA and ALB levels, lower Karnofsky performance status scores, and higher PG-SGA scores (P?<?0.05), and there was no relationship with CHOL and TG levels. Weight loss in the previous 1?mo was seen with CRP positive patients (P?<?0.05).
Conclusion: Almost 50% of malignant tumor patients had elevated serum CRP levels indicating a systemic inflammatory state. The nutritional status was worse in cancer patients with higher concentrations of serum CRP. The level of CRP was associated with the tumor stage, and, as stage is a prognostic factor, so can CRP be used as a prognostic maker in malignant tumors patients. 相似文献
Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) have poor prognosis, and the efficacy of chemotherapy plus tyrosine kinase inhibitors (TKIs) followed by mismatched donor stem cell infusion (microtransplantation, MST) has not been determined. We retrospectively summarized 45 patients including 11 undergoing MST with TKIs, 17 receiving allogeneic transplant and 17 undergoing chemotherapy with TKIs. Improved 4-year overall survival rate was observed in the MST group (91%) compared with either transplant group (31%, P = .005) or chemotherapy group (36%, P = .013). The MST group also had higher 2-year and 4-year leukemia-free survival rates (91% and 72%, respectively) compared with either transplant group (33%, P = .005 and 33%, P = .021, respectively) or chemotherapy group (41%, P = .017 and 31%, P = .023, respectively). 2-year and 4-year cumulative incidences of hematologic relapse were lower in the MST group (9% and 28%, respectively) compared with those in the chemotherapy group (56%, P = .025 and 67%, P = .034, respectively). In patients undergoing MST, donor microchimerism was detected (1.07 × 10-5 to 6.6 × 10-4 copies from 9 to 1499 days) in 7 patients, and donor/patient-derived HLA*0201/2402+WT1+CD8+ T cells were found from 0.05% to 0.67% in 6 patients. MST may provide a favorable treatment for patients with Ph+ ALL. 相似文献
Objective To screen Oxalobacter formigenes (OxF) from fresh feces of healthy adults, and study its effect on the the prevention of calcium oxalate kidney stones. Methods OxF was screened and cultured from fresh feces of healthy adults. The rat model of calcium oxalate stone was established by esophageal gavage of 0.8% of ethylene glycol. Rats were divided into a control group and four groups of rats with ethylene glycol-induced calcium oxalate kidney stones according to random number table. Three groups were treated with 106 CFU, 107 CFU, 108 CFU viable OxF every day, respectively, for 4 weeks. The blood and 24-hour urine samples were collected to detect the serum creatinine, urea nitrogen, serum and urine calcium, phosphorus, magnesium and urine oxalate every week. At the end of the 4th week, the rats were sacrificed and the kidney tissues were stained with HE and Yasue. The deposition and content of calcium oxalate crystals were observed under a light microscope. Results The bacteria strain isolated from fresh feces of healthy adults was 100% as same as the known ATCC35274 bacteria strain, which means the strain screened is OxF. Among the 5 groups, there were no significant differences in body weight, Scr, BUN, serum calcium, blood magnesium, blood phosphorus, urinary magnesium and urinary phosphorus. The 24-hour urinary calcium excretion in the model group was significantly lower than that of the control group (P<0.05). After intervention with OxF solution, the 24-hour urinary calcium excretion in the 108 CFU OxF group was significantly higher than that in the model group (P<0.05), while there was no significant difference between the other intervention groups and the model. The oxalic acid excretion of 106 CFU OxF group and 107 CFU OxF group was lower than that of the model, but the difference did not reach statistical significance (P>0.05). The 24 h oxalic acid excretion in the 108 CFU OxF group was significantly lower than that of the model at the end of first week (P<0.05), and continued to decrease for the next 3 weeks. After 4 weeks of intervention, no crystal formation was observed in the control group under the deflection microscope, but a large amount of calcium oxalate crystals were formed in the renal cortex and renal medulla. The crystals were piled up and connected to each other. Yasue staining coincided with the calcium oxalate crystal in the same part of the kidneys. Compared with the model, there was no significant change in the score of calcium oxalate crystal in the kidneys of 106 CFU OxF group and 107 CFU OxF group, while the score of calcium oxalate crystal in the kidneys of 108 CFU OxF group was significantly lower (P<0.05). Conclusions OxF are successively screened from healthy adults. Daily administration of 108 CFU OxF can safely and effectively reduce the urinary oxalic acid excretion, prevent the formation of calcium oxalate crystals and inhibit the formation of stones in kidneys of rats. 相似文献