Changes of T Cell Subsets and Their Relationship with Clinical Features and Prognosis in Patients with Acute Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the relationship between T cell subsets and clinical data.</p><p><b>METHODS</b>mononuclear cells were collected from 103 patients with acute leukemia (AL) and 28 healthy volunteers, and percentage changes of CD3CD4, CD3CD8 and CD4 CD25 Foxp3 cell subsets were assayed by flow cytometory. Relationship between the T subsets and clinical features of the patients was analyzed.</p><p><b>RESULTS</b>Ratio of CD3 T cells decreased more significantly in patients with >50% blast cells than that in patients with <50% blast cells, while the ratio of Treg between the 2 groups was not significantly different. Treg increased more statistically significantly in the patients with CD34 leukemia cell than that with CD34 leukemia cells. In constrast to the relationship between prognosis and immune cells in the patients from 3 groups (low, intermediate and high-risk group) it was found that Treg cells increased more significantly in high-risk group than that in low-risk group. By continuously monitoring immune cells in 18 patients, it was found that Treg cells gradually increased during the first 3 courses of chemotherapy, then began to decreased in the 4th course, finally approached gradually to the normal value in the 6th course, and this change correlated with the clinical remission after chemotherapy. Treg cell number in the patients with AL was significantly higher than that in healthy controls, and Treg cell number during the onset and recurrence was significantly higher than that in the period of complete remission (continuous remission for over 6 months). Compared with the changes of immune cell number between different types of disease, it was found that Treg cells were increased more significantly in acute myeloid leukemia (AML) than that in acute lymphoblastic leukemia (ALL). Proportion of Treg cells, Treg/CD4 decreased more significantly after the 1st course of chemotherapy in the group with complete remission (CR) than that in the group without CR. The complete remission rate and recurrence rate were 68.9% and 20% respectively in the group with >10% Treg cells, while the complete remission rate and recurrence rate were 85.7% and 7.69% respectively in the group with.<10% Treg cells. In comparison of the 6 recurrent patients with 32 patients with sustained CR, it was found that the ratio of Treg cells and Treg/CD4 was increased more significantly in the patients with relapse than that with CR and in control group.</p><p><b>CONCLUSION</b>Dynamic change of Treg cells in the peripheral blood was closely related with clinical feature, recurrence and prognosis in the patients with acute leukemia.</p>

HBeAg seroconversion achieved by sequential peginterferon alfa-2a therapy in chronic hepatitis B patients with unsatisfactory end point following entecavir treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of peginterferon alfa-2a (Peg-IFNa-2a) therapy for treating chronic hepatitis B (CHB) in patients who failed to achieve a satisfactory end point with entecavir (ETV) treatment.</p><p><b>METHODS</b>Fifty-seven CHB patients with positivity for hepatitis B e antigen (HBeAg) who had completed a standard ETV monotherapy course, of at least 96 weeks, and who had achieved a virological response (defined as HBV DNA less than 500 copies/ml) but without HBeAg seroconversion (defined as 0.227 PEI U/ml less than HBeAg less than or equal to 50 PEI U/ml) were enrolled in the study. The patients were randomly assigned to receive a 48-week treatment with Peg -IFNa-2a (experimental group, n = 27) or continued ETV therapy (control group, n = 30). Serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. Inter-group differences were statistically evaluated by t-test or Chi-squared test.</p><p><b>RESULTS</b>The baseline levels of alanine aminotransferase, hepatitis B surface antigen (HBsAg), and HBeAg were similar between the patients comprising the experimental and controls groups. At treatment week 48, the experimental group showed significantly higher rates of HBeAg clearance (Peg-IFNa-2a: 40.7% vs. ETV: 16.7%, x2 = 4.079, P less than 0.05) and seroconversion (37.0% vs. 13.3%, x2 = 5.110, P less than 0.05). The experimental group also showed higher rates of HBsAg clearance (7.4% vs. 0%) and HBV DNA relapse (11.1% vs. 0%), but the differences did not reach statistical significance (x2 = 2.307 and 3.519, both P more than 0.05). However, the level of HBsAg was significantly lower in the experimental group (2866.0+2580.4 vs. 4335.8+2650.0 IU/ml, t = 5.11, P less than 0.05).</p><p><b>CONCLUSION</b>HBeAg-positive CHB patients with unsatisfactory response to initial ETV monotherapy achieved HBeAg seroconversion and clearance following sequential Peg-IFN a-2a treatment.</p>

Prevalence and clinical characteristics of thyroid disease induced by chronic hepatitis B treated with polyethylene glycol (peg) interferon-alpha / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the prevalence and clinical characteristics of thyroid disease induced by chronic hepatitis B treated with polyethylene glycol (peg) interferon-alpha.</p><p><b>METHODS</b>Totally 210 patients with chronic hepatitis B were monitored for thyroid function and thyroid antibodies before application of polyethylene glycol (peg) interferon-alpha therapy and every 3 months during and after the treatment.</p><p><b>RESULTS</b>After treatment with polyethylene glycol (peg) interferon-alpha, 6.7% (14/210) of patients had thyroid disease, in which 5.2% (11/210) had hyperthyroidism and 1.4% (3/210) had hypothyroidism. The proportion of the hyperthyroidism and hypothyroidism in women were 11.8% (6/51) and 3.9% (2/51), higher than 3.1% (5/159) and 0.6% (1/159) in male (P < 0.05). In women subjects, higher proportion of those who developed thyroid disease were positive for antibody against thyroid peroxidase (TPOAb) before treatment and positive for antibody against thyroid globulin (TgAb) during the treatment as compared with those who did not develop thyroid disease (P < 0.05).</p><p><b>CONCLUSION</b>Patients with chronic hepatitis B treated with polyethylene glycol (peg) interferon-alpha therapy are prone to develop thyroid disease. Women positive for TPOAb and TgAb may be at increased risk for developing thyroid disease.</p>

Efficacy of lamivudine and adefovir de novo combination therapy or after mono-therapy in chronic hepatitis B patients / 中华肝脏病杂志

To investigate the efficacy of 104 weeks of lamivudine (LAM) and adefovir (ADV) de novo combination therapy, as compared to optimized combination therapy administered after 48 weeks of treatment with lamivudine or adefovir mono-therapy, in chronic hepatitis B (CHB) patients. A total of 174 patients with CHB were equally divided among three treatment groups: LAM mono-therapy; ADV mono-therapy; and LAM + ADV combination therapy. The patients in the LAM + ADV group were treated with LAM plus ADV for 104 consecutive weeks. The patients in the LAM or the ADV groups were first treated for 48 weeks with LAM or ADV, respectively, after which the patient's virological response was assessed. According to the results, the patient was continued on mono-therapy or switched to combination therapy for the subsequent 56 weeks. Virological and biochemical examinations were carried out at weeks 48 and 104. The rates of undetectable HBV DNA in the LAM mono-therapy, ADV mono-therapy, and LAM-ADV combination therapy groups at week 48 were 68%, 50%, and 84%, and at week 104 were 80%, 72%, and 95%, respectively. For the same groups, the virus breakthrough rates at week 48 were 15%, 0%, and 0%, and at week 104 were 18%, 2%, and 0%, respectively. Statistical analysis showed significant differences for the rate of undetectable HBV DNA between LAM + ADV group and LAM group at week 48 (x2 = 4.473, P= 0.034) and at week 104 (x2 = 5.795, P = 0.016), LAM + ADV group and ADM group at week 48 (x2 = 14.802, P less than 0.001) and week 104 (x2 = 5.547, P = 0.001). The hepatitis B e antigen (HBeAg) seroconversion rates at week 48 were 15% (x2 = 4.543, P = 0.033), 13% (x2 = 4.035, P = 0.045) and 38%, and at week 104 were 21% (x2 = 4.438, P = 0.035), 17% (x2 = 4.223, P = 0.04) and 44%, respectively, among patients positive for HBeAg. Statistical analysis showed that the differences among the three groups for each of these parameters were statistically significant (all, P less than 0.05). When compared with LAM or ADV mono-therapy followed by LAM+ADV at week 48, the LAM plus ADV de novo combination therapy for 104 weeks provided CHB patients with better virological and serological responses and a lower drug resistance rate.

Study on the efficacy and HBeAg seroconversion related factors of telbivudine and entecavir therapy in HBeAg positive chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of Telbivudine and Entecavir for therapy of HBeAg positive chronic hepatitis B for 52 weeks.</p><p><b>METHODS</b>In this random and control study, the efficacy of Telbivudine and Entecavir treatments were compared in 180 patients with HBeAg positive chronic hepatitis B.The patients were randomly assigned to a daily 600 mg Telbivudine treatment group or daily 0.5 mg Entecavir group for 52 weeks.</p><p><b>RESULTS</b>At week 52, HBV DNA undetectable rate was better in the Entecavir-treated group than in the Telbivudine-treated group, but didn't reach statistical significance. The viral breakthrough rates were significantly lower in the Entecavir-treated group than in the Telbivudine-treated group (x2 = 4.09, P <0.05). The clearance and seroconversion of HBeAg and the mean reductions of HBeAg from baseline at week 52 were significantly greater in the telbivudine-treated group than in the entecavir-treated group (x(2) clearance = 4.63, x(2) seroconversion = 4.80, (t-mean) reductions = 2.02; P < 0.05). The HBeAg seroconversion rates were not associated with both baseline ALT and baseline HBV DNA in both groups (P more than 0.05). In Telbivudine-treated group, the HBeAg decline is more than 2 log at week 24, HBeAg decline is more than 1 log at week 12 and the HBeAg baseline were independent factors correlated to HBeAg seroconversion rates at week 52 by Binary Logistic analysis, and also in entecavir-treated group the HBeAg decline is more than 2 log at week 24, HBeAg decline is more than 2 log at week 36 and the HBeAg decline is more than 2 log at week 12 were independent factors correlated to HBeAg seroconversion rates at week 52.</p><p><b>CONCLUSION</b>Significant difference of HBeAg seroconversion rates at week 52 existed between Telbivudine-treated group and Entecavir-treated group. Entecavir is significantly superior to Telbivudine with less resistance to nucleosides. HBeAg decline is more than 2 log at week 24 is the best predicting factor for HBeAg seroconversion at week 52.</p>

Individualized respond guidance treatment of chronic hepatitis C with combination of peginterferon α-2a and ribavirin / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study individualized treatment of chronic hepatitis C (CHC) genotype 1 patients using respond guided therapy (RGT) of peginterferon α-2a in combination with ribavirin.</p><p><b>METHODS</b>140 patients with CHC genotype 1 received peginterferon α-2a 180 microg injection once a week in combination with ribavirin 800-1200 mg/d. Patients achieved RVR after 4 weeks treatment (group A) were randomized into 2 subgroups and proceeded with 24 and 48 weeks treatments (subgroups A1 and A2) respectively. Patients who had not received RVR but achieved cEVR at week 12 (group B) were further divided into 2 subgroups randomly and treated for 48 and 72 weeks (subgroups B1 and B2), respectively. Patients with PVR at week 24 were treated for 72 weeks (group C1), while patients without PVR at week 24 discontinued treatment (group C2). All Patients were followed-up for 24 weeks after the end of treatment.</p><p><b>RESULTS</b>For patients treated for 24 weeks, the ETR rate was 100%, the SVR rate was 65.9%, and the relapse rate was 34.1%. For those treated for 48 weeks, the ETR, SVR and relapse rate were 95.3% , 82.8% and 12.5% respectively. For those treated for 72 weeks, the above rates were 82.1%, 67.9% and 14.3% respectively. SVR rates of subgroup A1 and A2 were 65.9% and 84.4% respectively and the difference was statistically significant (P<0.00). The HCV RNA loads were less than 1x10(6) copy/ml in group A and the SVR were 72.7% and 100% respectively with 24 and 48 weeks treatment, and the difference was insignificant statistically (P>0.05). SVR in subgroup B1 and B2 were 78.9% and 73.7% respectively and the difference was statistically insignificant (P>0.05). The SVR in group C1 was raised to 55. 6%.</p><p><b>CONCLUSIONS</b>RVR and cEVR were respond guided prediction factors for CHC treatment. SVR among patients with RVR was higher in 48-week treatment than those with 24 weeks treatment. For patients with baseline virus load less than 1x10(6) copy/ml and achieved RVR, treatment duration can be shortened to 24 weeks. Treatment extension to 72 weeks can not result in SVR increase among patients without RVR but with cEVR. However, treatment extension to 72 weeks can increase SVR among those patients with PVR.</p>

Study on relationship between chemical castration and thymic function following hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Murine model of MHC mismatched allogeneic HSCT (C57BL/6-->BALB/c) was established. The severity of acute graft-versus-host-disease (GVHD) was assessed according to a clinical scoring system. The intra-cellular levels of IFN gamma, TNFalpha and IL-1 beta in thymocyte were analyzed by protein array and thymic function by quantification of signal-joint TCR rearrangement excision circles (sjTRECs).</p><p><b>RESULTS</b>All recipients in group A (allogeneic mice), B (allogeneic LHRH castrated-mice) and C (syngenic mice) achieved hematopoietic reconstitution. White blood cell (WBC) over 1.0 x 10(9)/L in groups A, B and C were on day (11.2 +/- 1.4), day (9.8 +/- 0.6) and day (9.7 +/- 0.7), respectively (P = 0.003, 0.002). The onset of acute GVHD in group B was (14.1 +/- 0.7) d and in group A was (11.4 +/- 1.2) d (P = 0.000). All mice in groups A and B developed acute GVHD. No mice occurred aGVHD in group C. The average scores of acute GVHD in groups A and B were (9.1 +/- 0.7) and (5.1 +/- 1.0), respectively (P = 0.000). The levels of IFN gamma, TNFalpha and IL-1 beta in control group were (2.3 +/- 2.5) ng/ml, (1.7 +/- 1.1) pg/ml and (1.8 +/- 1.2) pg/ml, respectively. The IFN gamma levels in groups A, B and C were (10.5 +/- 2.1) ng/ml, (6.7 +/- 2.1) ng/ml and (5.2 +/- 3.3) ng/ml, TNFalpha levels were (7.0 +/- 2.6) pg/ml, (4.3 +/- 0.8) pg/ml and (3.0 +/- 1.8) pg/ml, and IL-1 beta levels were (24.9 +/- 9.0) pg/ml, (17.4 +/- 3.9) pg/ml and (10.8 +/- 3.1) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P = 0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those in control group (P = 0.000, 0.003, 0.000). The levels of IFN gamma and IL-beta in group C were significantly higher than those of in control group (P = 0.015, 0.013), and so did in group A than in group B (P = 0.002, 0.002, 0.004), and in group A than in group C (P = 0.000, 0.000, 0.000). The analysis of linear regression showed that the average levels of IFN gamma and TNFalpha paralleled with aGVHD scores (r(2) = 0.359, P = 0.045; r(2) = 0.228, P = 0.019). The average sjTRECs copies/1000 PBMNCs were (39.4 +/- 44.7) in the control group and (12.3 +/- 13.0), (58.0 +/- 71.8) and (19.6 +/- 14.6) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P = 0.468).</p><p><b>CONCLUSION</b>IFN gamma, TNFalpha and IL-1 beta might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intra-cellular levels of IFN gamma in thymocyte.</p>