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Objective@#To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) .@*Methods@#In this study we retrospectively analyzed 158 Ph+ ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy.@*Results@#Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ2=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ2=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ2=7.908, P=0.005) .@*Conclusions@#Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph+ ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.
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Objective@#To investigate the relationship between donor chimerism and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#The clinical data of 105 patients with acute myeloid leukemia (AML) who underwent allo-HSCT and recurrence-free survival>90 days from January 2010 to January 2019 were retrospectively analyzed. The bone marrow samples were collected at 15, 30, 60, 90, 180, 270, 360 days after transplantation. Donor chimerism was detected by single nucleotide polymorphism (SNP) -PCR.@*Results@#Of the 105 patients, 43 cases were male and 62 cases were female, with a median age of 38 (16-60) years. Till April 2019, the median follow-up was 843 (94-3 261) days. Ninety days after transplantation, 18 cases relapsed, 33 cases died, and 72 cases survived. The 3-year overall survival (OS) rate was (66.8±5.1) %, and the recurrence-free survival (RFS) rate was (65.1±5.0) %. Pre-transplant disease status, pre-transplant minimal residual disease (MRD) , and 90 day post-transplantation chimerism were independent risk factors related to RFS. The risk of recurrence was significantly increased in patients with a donor chimerism rate ≤97.24% at 90 days after transplantation[HR=6.921 (95%CI 2.669-17.950) , P<0.001], which was considered as a sign of early relapse.@*Conclusion@#SNP-PCR is an applicable method for detecting donor chimerism in patients after allo-HSCT. Chimerism rate equal or less than 97.24% at 90 days after transplantation predicts a higher risk of relapse.
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Objective To determine the effect of cardiomyopeptidin on transient outward potassium current(I_(to) of rat ventricular myocytes and its action mechanism on the ion channels of myocardium.Methods Single ventricular myocytes of rats were obtained by enzymatic dissociation.The whole-cell patch-clamp recording technique was used to record the change of transient outward potassium current(I_(to) by different dosages of cardiomyopeptidin.Results Cardiomyopeptidin decreased I_(to) in a dose-dependent manner.Cardiomyopeptidin in dose of 10,50,100,250 and(500 mg/L) decreased I_(to %) by 4,13,22,32 and 38 respectively.Cardiomyopeptidin 50 mg/L moved the current density-voltage curve of I_(to) down,but the shape of the curve had no changes.Cardiomyopeptidin 50 mg/L did not change the steady state activation curve of I_(to).Conclusions Cardiomyopeptidin decreases the I_(to) of rat ventricular myocytes,which might be one of the mechanisms of its antiarrhythmic effect.
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Objective To study the effect of ketamine on L-type calcium currents (ICa-L) in guinea pig ventricular myocytes. Methods Adult guinea pigs of both sexes were anesthetized with pentobarbital. The hearts were immediately removed and ventricular myocytes were prepared by the technique described by Liu et al. The whole-cell patch clamp technique was used to study the ICa-L in isolated guinea pig ventricular myocytes. The changes in ICa-L produced by ketamine 100 ?mol?L-1 with different holding potentials or by different concentrations of ketamine with holding potential of + 10 mV were analyzed. Results Ketamine dose-dependently inhibited ICa-L evoked by a voltage step from a holding potential of - 40 mV to + 10 mV. The 4 concentrations of ketamine (100, 500, 1 000, 5 000 ?mol?L-1) reduced 1Ca-L by 28.7%?5.7% , 34.7%?1.4%, 58.7%?6.4% and 81.7%?6.7% respectively, with a mean IC50 concentration of 926.6 ?mol?L-1 . When the cells were exposed to ketamine 100 ?mol?L-1, the steady-state activation curve was not significantly affected, while the steady-state inactivation curve was shifted to more negative potentials.V1/2 decreased from ( - 14.8?0.8 ) mV to ( - 19.6?0.7) mV (P0.05) in control and drug-affected cells respectively. Ketamine slowed the rate of recovery from inactivation. Conclusion Ketamine can inhibit ICa-L in guinea pig ventricular myocytes in a concentration-dependent manner. This inhibitory effect of ketamine may explain its negative inotropic effect. Ketamine inhibits L-type calcium channel in its inactivated state.
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Objective To study the effect of ketamine on inward rectifier potassium currents(I_k1)in isolated rat ventricular myocytes using whole-cell patch clamp technique.Methods Adult Wistar rats of both sexes were anesthetized with pentobarbital.The hearts were removed and ventricular myocytes were prepared by the technique described by Liu et al.Whole-cell patch clamp technique was used to study I_(k1) in isolated rat ventricular myocytes The changes in I_(KI) produced by 100 ?mol?L~(-1) with different holding potentials or by different concentrations of ketamine with holding potential of-120 mV were analyzed.Results Ketamine 100 ?mol?L~(-1) inhibited the Ira without any significant effects on reverse potential (-50--60 mV)and the shape of the Ⅰ-Ⅴ curve.Ketamine inhibited I_(k1) evoked by a holding potential of-120 mV in a dose-dependent manner with a mean IC_(50) value of (162.3?8.4)?mol?L~(-1).Conclusion Ketamine significantly inhibits I_(k1) in ventricular myocytes. This may explain the prolonged duration of action potential of ventricular myocyte produced by ketamine.
