Comparison of clinical efficacy between first-generation and second-generation tyrosine kinase inhibitors based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia / 中华血液学杂志

Objective: To explore the clinical efficacy and prognostic factors of first-generation and second-generation tyrosine kinase inhibitors (TKI) based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia (ALL) . Methods: Retrospectively analyze the clinical characteristics and prognostic factors of 89 patients with BCR-ABL positive ALL from April 2012 to June 2018 in our hospital, the clinical efficacy of first-generation and second-generation TKI was compared. Results: 60 patients were classified into the first-generation TKI (imatinib) group, and 29 patients were in the second-generation TKI (dasatinib) group. There were no significant differences in gender, age, WBC, hemoglobin concentration, PLT, chromosomal karyotype, the types of fusion genes, allogeneic hematopoietic stem cell transplantation (allo-HSCT) and TKI initiation time between the two groups. The first-generation and second-generation TKI groups, for which the complete remission (CR) rate at the fourth week of induction therapy was 83.3% and 89.7% (P=0.637) , respectively, and the complete molecular remission (CMR) was 48.3%and 58.6% (P=0.363) , respectively, the difference was not statistically significant. The 2-year overall survival (OS) rate of first-generation and second-generation TKI group was 34.9% and 64.0% (χ(2)=4.743, P=0.029) , the 2-year relapse free survival (RFS) rate was 17.2% and 55.0% (χ(2)=8.801, P=0.003) , respectively. Multivariate analysis showed that complete molecular remission (HR=0.281, 95%CI 0.151-0.523, P<0.001) was independent favorable prognostic factor for overall survival (OS) , complete molecular remission (HR=0.209, 95%CI 0.112-0.390, P<0.001) and second-generation TKI (HR=0.318, 95%CI 0.158-0.641, P=0.001) were independent favorable prognostic factors for RFS. Conclusion: For TKI-based regimen of BCR-ABL positive ALL, second-generation TKI is superior to first-generation TKI in OS and RFS time.

Hyperthermia increases the sensitivity of RPMI 8226 cells to adriamycin / 中国实验血液学杂志

This study was purposed to explore the effect of hyperthermia on sensitivity of multiple myeloma cells RPMI 8226 to adriamycin (ADM) and its mechanism. The working concentration of ADM against RPMI 8226 cells was defined by MTT assay. RPMI 8226 cells were divided into 4 groups: control group, hyperthermia (42°C) group, chemotherapy (ADM) group and combination group (42°C + ADM), the survival rate of RPMI 8226 cells in 4 groups was detected by trypan blue exclusion, the inhibitory effect of hyperthermia on proliferation of RPMI 8226 cells was detected by MTT assay, the cell cycle distribution, apoptosis rate of cells, intracellular ADM concentration and P-gp expression level were measured by flow cytometry. The 1/4 IC(50) of ADM was defined as the working concentration in the experiment. The results indicated that the hyperthermia promoted the entering the cells from in G(0)/G(1) phase into S and G(2)/M phases, the expression of P-gp protein on cells in hyperthermia and combination groups was down-regulated, the intracellular ADM concentration in combination group obviously increased. It is concluded that the hyperthermia combined with ADM obviously enhance the inhibitory effect on proliferation of RPMI 8226 cells. The hyperthermia increases the sensitivity of RPMI 8226 cells to chemotherapy through down-regulating the expression of P-gp protein on cells and increasing the intracellular ADM concentration.

The efficacy of high-dose cytarabine for patients with t(8;21) AML and with normal karyotype AML / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy of high-dose cytarabine (HD-Ara-C) based chemotherapy for post-remission treatment in patients with t(8;21) (q22;q22) AML-M2 and those with normal karyotype AML-M2.</p><p><b>METHODS</b>AML-M2 patients were grouped into with (21 cases) or without (23 cases) t(8;21) (q22;q22) karyotype groups. After achieved remission by induction therapy, all patients received four cycles of HD-Ara-C (3 mg/m2 per 12 hours by three-hour infusion day 1 to day 3) with either mitoxantrone (7 mg m(-2) d(-1)) or aclarubicin (30 mg m(-2) d(-1)) or etoposide (70 mg m(-2) d(-1)) for 3d as post-remission treatment.</p><p><b>RESULTS</b>Relapse rate in the t(8;21) and the normal karyotype groups was 29% and 57% respectively (P<0.05); 3 year disease-free survival (DFS) rate was 71% and 43% respectively (P < 0.05). and 3 year over-all survival (OS) rate was 76% and 65% respectively (P >0.05).</p><p><b>CONCLUSION</b>Four cycles of high-dose cytarabine based combination chemotherapy as post-remission treatment improves long-term disease-free survival in patients with t(8;21) (q22;q22) AML-M2.</p>

Detection and screening for human cytomegalovirus infection in allogeneic hematopoietic stem cell transplantation recipients by different methods / 中国实验血液学杂志

The aim of study was to explore the better detection method for cytomegalovirus (CMV) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients and to compare the efficiency of fluorogenic quantitative PCR (FQ-PCR), flow cytometry (FCM) and ELISA. The plasma DNA loading and serum level of IgM antibody against CMV in 214 clinical specimens from 19 allo-HSCT patients were detected by real-time FQ-PCR and ELISA respectively, the pp65 antigen in 118 peripheral blood leukocyte samples were measured by FCM. The results showed that the positive rates of pp65 antigen, IgM antibody and DNA load were 30.85% (58/188), 13.08% (28/214) and 35.51% (76/214) respectively, the coincidence between their sequential detection positive rates and clinical diagnosis were 7/8, 7/8 and 3/8 respectively. There was no statistical significant difference between the positive rate of pp65 antigen and of DNA amount (P > 0.05), and they have manifested relationships (P < 0.05). The positive rate of IgM antibody detected by ELISA was obvious lower than that of DNA quantitated by FQ-PCR and pp65 antigen detected by FCM, but the difference between them showed statistical significance (P < 0.05), Smaller relativity was found between IgM antibody detection and the other two methods (P > 0.05). It is concluded that FQ-PCR and FCM are sensitive, rapid, suitable and reliable methods for monitoring recipient reactive CMV infection of allo-HSCT recipients and are worthy to extensively use for guiding antiviral therapy.

Application of all-trans retinoic acid combining chemotherapy and As4S4 in the maintenance treatment of patients with acute promyelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy of all-trans retinoic acid (ATRA) combining chemotherapy and As4S4 with ATRA combining chemotherapy for the maintenance treatment of patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Sixty patients with APL induced to complete remission by ATRA and consolidated by chemotherapy were randomly divided into two groups. Thirty patients as As4S4 group received ATRA + As4S4 + chemotherapy, and another thirty patients as non-As4S4 group were treated only with ATRA + chemotherapy as maintenance therapy. The therapeutic effects, side effects and PML-RARalpha gene expression were analyzed.</p><p><b>RESULTS</b>The three-year continuous complete remission (CCR) rate was 90.0% for As4S4 group and 61.1% for non-As4S4 group, the difference being statistically significant. Significant difference was also found in the positive rate of PML-RARalpha fusion gene between the two groups. The side effects were mild.</p><p><b>CONCLUSION</b>APL patients in maintenance therapy with ATRA + 6-MP + MTX + As4S4 can obtain a higher CCR.</p>

MEKK2 regulates the production of interleukin 2 / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the role of MEKK2 on the production of IL-2 in Jurkat cells stimulated by PHA/anti-CD28 antibody.</p><p><b>METHODS</b>The MEKK2 and JNK kinase activities were measured in both dominant negative MEKK2 Jurkat (dnMEKK2 Jurkat) cells and parental Jurkat cells. The AP(1) and IL-2 promotor activities were measured by luciferase activity assay. The IL-2 mRNA and protein were detected by RT-PCR and Western blot.</p><p><b>RESULTS</b>After stimulation by PHA/anti-CD28, JNK was activated in parental Jurkat cells but not in dnMEKK2 Jurkat cells. The luciferase report gene activities of AP1 and IL-2 promotors were increased by 4- and 5-folds in parental cells whereas only by 1 fold in dnMEKK2 Jurkat cells. The level of IL-2 mRNA and IL-2 protein were increased in parental Jurkat cells but not in dnMEKK2 Jurkat cells.</p><p><b>CONCLUSION</b>MEKK2 plays an important role on the production of IL-2 in Jurkat cell stimulated with PHA/anti-CD28 antibody. It is a potential drug target for the treatment of GVHD and autoimmune disease.</p>