Clinical analysis of 70 chronic lymphocytic leukemia patients with trisomy 12 detected by FISH / 中华血液学杂志

Objective@#To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12).@*Methods@#Clinical data of 330 CLL patients were analyzed retrospectively by using FISH (CEP12) to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients (70 cases) were compared with those CEP12 negative patients (260 cases).@*Results@#Compared with CEP12 negative CLL patients, the proportion of hepatomegaly (13.6% vs 4.0%, P=0.011) and LDH>247 U/L (43.3% vs 18.5%, χ2=15.892, P<0.001) in CEP12 positive CLL patients were much higher, respectively. There were no significant differences between age, sex, clinical stage, β2-microglobulin level, IGHV mutation ratio and splenomegaly/lymphadenopathy in these two subgroups. However, compared with CEP12 negative patients, CEP12 positive patients had higher ratio of FMC7 (23.8% vs 12.7%, χ2=4.730, P=0.030), and lower ratio of CD23 (95.2% vs 99.6%, P=0.033). The overall response rates (ORR) in Fludarabine (without Rituximab), Rituximab (with or without Fludarabine) and the traditional chemotherapy group (chlorambucil, CHOP or CHOP-like) were 77.5% (31/40), 84.8% (56/66) and 45.4% (50/110), respectively. The ORR of the traditional chemotherapy group was lower than that of the Fludarabine group and Rituximab group. For CEP12 positive patients, the ORR was inferior to CEP12 negative patients when only using Fludarabine (P<0.05). However, when using Rituximab, the difference could be eliminated, and the ORR was even a little higher in CEP12 negative patients (91.7% vs 81.0%, P=0.306). Compared with CEP12 negative patients, there were no significant differences in progression-free survival (PFS) (χ2=0.410, P=0.478) and overall survival (OS) (χ2=0.052, P=0.180) for CEP12 positive patients whom the median time from diagnosis to start treatment and OS time was 22.6 (95%CI 15.4-31.7) and 118.5 (95%CI 74.5-162.4) month while the 5-year PFS and OS were (52.9±7.6)% and (74.8±6.6)%.@*Conclusions@#CEP12 positive CLL patients are more common in hepatomegaly and higher level of LDH. The traditional chemotherapy treatment had the lowest efficacy, and the curative effect of single use of fludarabine is not as good as that of CEP12 negative patients, however, when using Ritaximab, the efficacy could be comparable.

Clinical and laboratory features of B-cell chronic lymphocytic leukemia: a retrospective analysis of 503 cases / 白血病·淋巴瘤

Objective To investigate the clinical and laboratory characteristics of patients with chronic lymphocytic leukemia (CLL). Methods 503 patients with CLL admitted from October 1998 to February 2015 were retrospectively analyzed. Baseline characteristics were compared using Chi-square test and Kaplan-Meier methodology was undertaken for survival analyses. Results The median age was 58 years (26-86 years):335 cases were male and 168 cases were female. 204 cases (40.5%) were at the clinical stage of Binet A, followed by Binet B (148 cases, 30.1%) and Binet C (151 cases, 29.3%). 108 cases (21.1%) had anemia at diagnosis, while 113 cases (26.5 %) had an elevated level of lactate dehydrogenase and the expression of CD38 was detected among 100 cases (29.1 %). Clonal abnormalities were observed using fluorescence in situ hybridization (FISH) analysis. Those involving 13q deletion were the most frequent (156 cases, 47.3 %), followed by IgH translocation (22.4 %), trisomy 12 (21.2 %) and 17p deletion (14.5 %). The mutational status of immunoglobulin heavy chain variable region was determined among 230 cases, 165 cases (71.7%) of which were found to be with mutated status. The most frequently encountered gene was V4-34 (28 cases, 12.4 %). The median progression-free survival (PFS) was 89.0 months (95 %CI 75.0-103.0 months), while the median overall survival was 129.0 months (95 %CI 106.9-151.1 months). Conclusion Compared with patients in the western world, CLL patients in this study are younger at diagnosis and have longer overall survival, which, to some extent, could reflects the characteristics of CLL patients in China.

Analysis of Clinical Characteristics for 24 Cases of Nodal Marginal Zone Lymphoma / 中国医学科学院学报

Objective To summarize and investigate the characteristics of nodal marginal zone lymphoma (NMZL). <strong>Method</strong> The clinical data and laboratory characteristics of of NMZL patients admitted in our hospital between January 2002 and September 2013 were analyzed retrospectively. <strong>Results</strong> Twenty-four patients were enrolled in the study. The median age was 54.4 (28-70) years,and the male/female ratio was 1:1. Most of the patients (95%) had bone marrow involvement,40.9% (9/22) had elevated lactate dehydrogenase level,8.3% (2/24) had the positive expression of hepatitis C virus antibody,33.3% (6/18) had positive autoimmune antibodies,and 33.3% (8/24) had monoclonal immunoglobulins in the serum. All of the patients expressed CD19 and CD20 cell markers,whereas none of them expressed CD10 cell marker. The positive rate of CD5 marker was 10% (1/10),the positive rate of CD23 marker was 50% (5/10),whereas no patient had the expressions of both CD5 and CD23 at the same time. The total overall remission rate was 81.25%,and the total complete remission rate was 56.2%. The separate overall remission and complete remission rate had increasing trends in rituximab subgroup than subgroups without using rituximab(P=0.136,P=0.262).<strong>Conclusion</strong> NMZL has a low incidence and can be seen in both males and females. It often invades bone marrow. Rituximab may increase the response rate and even improve the progression free survival.

Application and resistance mechanism of B-cell receptor signaling pathway inhibitors in lymphoma:reports from the 57th American Society of Hematology annual meeting / 白血病·淋巴瘤

With the recent success of B-cell receptor (BCR) signaling pathway inhibitor in the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL), a number of new agents targeting the BCR signaling pathway are in a clinical research stage. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. Studies have also found the drug resistance of BCR signaling pathway inhibitors, drawing attention of the mechanism and the way to overcome the drug resistance. Combined with the research progress reported in 57th American Society of Hematology (ASH) annual meeting, this article summarized the recent progress of BCR signaling pathway inhibitors and their resistance mechanism to provide new information on clinical therapy.

Correlation analysis of indolent B-cell non-Hodgkin lymphoma and hepatitis virus / 中国肿瘤临床

Objective:To differentiate hepatitis B virus (HBV) infection from hepatitis C virus (HCV) infection among different indolent B-cell non-Hodgkin lymphoma (B-NHL) subtypes. The correlation between indolent B-NHL and hepatitis viral infection was also investi-gated. Methods:A total of 733 indolent B-NHL patients from January 1994 to January 2014 with integrated clinical information were retrospectively investigated. We compared the hepatitis viral infection between the general population and indolent B-NHL patients. We analyzed the infection rate of hepatitis virus in the different indolent B-NHL subtypes and examined their correlations. Results:The HBs-Ag positive rate of the indolent B-NHL was 7.9%, which was not significantly different with that of the general population (7.9%vs. 7.2%, P=0.548). Among the different indolent B-NHL subtypes, the 48 splenic marginal zone lymphoma (SMZL) patients exhibited the highest HBs-Ag positive rate, which was significantly higher than those of the general population (18.8%vs. 7.2%, P=0.002), other indo-lent B-NHL subtypes (18.8%vs. 7.2%, P=0.004), and other marginal zone B-cell lymphoma (MZL) patients (18.8%vs. 7.1%, P=0.005). The HBs-Ag positive rates between other B-NHL subtypes and the general population were not significantly different. The coexpression of HBs-Ag, HBe-Ag, and anti-HBc-Ab exhibited no significant difference among the various B-NHL subtypes. However, the co-expres-sion of HBs-Ag, HBe-Ab, and anti-HBc-Ab was significantly higher in the SMZL group than the other B-NHL subtypes (16.7%vs. 4.7%, P<0.001).The positive rate of the anti-hepatitis C virus antibody (HCV-Ab) was 1.9%in 733 indolent B-NHL patients, which was significant-ly higher than in the general population (1.9%vs. 0.4%, P<0.001). The HCV-Ab positive rates in the chronic lymphocytic leukemia, lym-phoplasmacytic lymphoma/Waldenstr?m macroglobulinemia, SMZL, hairy cell leukemia, nodal marginal zone B-cell lymphoma group were 2.2%, 2.5%, 4.2%, 3%, and 3.7%, respectively. These values were significantly higher than those of the general population. Preva-lence rates of HCV in B-cell lymphoproliferative disorders, unclassified, extranodal marginal zone B-cell lymphoma of mucosa-associat-ed tissue lymphoma, B-cell prolymphocytic leukemia, and follicular lymphoma groups were not significantly different compared with the general population. Conclusion:Prevalence rate of HBV was higher in the SMZL group than other indolent B-NHL groups, which suggests that HBV infection may play an etiologic role in SMZL.

Prognostic effects of novel agents on cytogenetic abnormalities of multiple myeloma / 白血病·淋巴瘤

Multiple myeloma (MM) is a heterogeneous disease with certain cytogenetic abnormalities [1q21 gains,t(4;14),del 17p] associated with worse outcome.The extensive use of thalidomide,lenalidomide and bortezomib has dramatically improved the outcome for patients with MM and some cytogenetic abnormalities.It is also widely proved that bortezomib can partly overcome the harmful affects of t (4;14).However,till now,there are many controversies about the effects of some novel agents worked on certain cytogenetic abnormalities.In this review,the effects of novel agents in cytogenetic abnormalities were summaried to provide new information on clinical treatment of this disease.

Rituximab combined with second line regimens for treatment of seven relapsed and refractory Hodgkin lymphoma patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of Rituximab combined with second line regimen for treatment of relapsed and refractory Hodgkin lymphoma.</p><p><b>METHODS</b>Seven patients with relapsed and refractory Hodgkin lymphoma were treated with Rituximab combined with second line regimen. Among them, two patients were treated with R-GDP (E) [rituximab, gemcitabine, cisplatin, dexamethasone (etoposide)] regimen, another two patients with R-IGVP (rituximab, ifosfamide, gemcitabine, vinorelbine, prednisone)regimen, and the left three patients with R-BEACOPP (rituximab, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)regimen. The efficacy and safety were evaluated during and after chemotherapy.</p><p><b>RESULTS</b>There're three male and four female patients, whose median age was 21 years (range 12-36 years) old. One patient was diagnosed as nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), and the other six patients as classical HL (four nodular sclerosis HL, one lymphocyte-rich classical HL and one hmixed cellularity HL). The median cycles of salvage therapy were 4(1-4), and the median follow-up was 29 months (24-58 months). Among these 7 patients, the complete remission was observed in 4 patients, stable disease in 2 patients, but one patient died during salvage therapy. The two-year survival rates were 85.7% and the major toxic effects were bone marrow suppression.</p><p><b>CONCLUSION</b>These results indicate that the Rituximab combined with second line regimen is an effective therapy for relapsed and refractory Hodgkin lymphoma.</p>

Synergistic effect of vorinostat and melphalan on human multiple myeloma cell lines / 肿瘤研究与临床

Objective To observe the anti-tumor effect on human multiple myeloma cell lines U266 and KM3 with a combination of varinostat and melphalan in vitro.Methods The cell proliferation of U266 and KM3 was datected with MTT assay when treated them with vorinostat alone and melphalan alone,then calculate their IC50 values respectively.Fixed the concentrations of vorinostator melphalan,the cell proliferation was datected in combination with melphalan/vorinostat in seriesly concentrations by MTr assay.Then to calculate drug combination index(CI).Results The IC50 value of U266 was 5.0-7.5 μmol/L and that of KM3 was 2.5-5.0 μmol/L when treated by vorinostat alone,the IC50 value of U266 was 40-60 μmol/L and that of KM3 was 60-80 μmol/L treated by melphalan alone.When fixed the concentration of vorinostat(in U266 the concentration was 1.25 μmol/L,in KM3 the concentration was 1.0 μ mol/L),Synergism(CI＜0.9)was observed when the concentrations of melphalan were 20 μmol/L,40 μmol/L,60 μ mol/L and 80 μ mol/L in U266,40 μmol/L,60 μmol/L,80 μmol/L and 100 μmol/L in KM3;When fixed the concertration of melphalan (in U266,was 10 μmol/L,in KM3 was 20 μmol/L),synergism(CI＜0.9)was observed when the concentrations of vorinostat were 1.0 μmol/L,2.5 μmol/L,5.0 μmol/L and 7.5 μmol/L in U266,and 1.0 μmol/L,2.5μmol/L,5.0 μmol/L in KM3.An additive effect was observed with the czombination of vorinostat 7.5 μmol/L plus melphalan 20 μmol/L in KM3(CI=0.93).Conclusion Vorinostat had potential anti-myeloma effect alone,and had synergistic anti-tumor effect with melphalan in vitro.

Inhibitional effect of small hairpin RNA on expression of MRPI gene in K562/AS2 cell line resistant to As2O3 / 白血病·淋巴瘤

Objective To investigate the inhibitional effect of MRPI-shRNA on expression of MRP1gene in K56.2/AS2 cells resistant to arsenic trioxide. Methods Three pieces of MRPI-shRNA were designed,synthesized and transfected into K562/AS2 cells with lipesome. Expression level of MRPI mRNA were determined by real time fluorescent quantitative PCR. MRPI protein expression and intracellular accumulation of DNR were assayed with flow cytometry. Results After treated with MRPI-shRNA, the expression level of MRPI mRNA and MRPI protein in K562/AS2 cells decreased significantly(79.1±0.07) % and (62.48±0.86) %,respectively (P <0.05). The intracellular accumulation of DNR increased significantly(P < 0.05). Conclusion MRPI-shRNA can down-regulate the expression of MRPI gene in K562/AS2 cell line.

Treatment of BXSB With Allogeneic Hematopoietic Stem Cell Transplantation / 中华皮肤科杂志

Objective To investigate the efficacy,safety of allogeneic hematopoietic stem cell transplantation(Allo-HSCT)in lupus mice.Methods22BXSB was pre-treated with myleran and cyclophosphamide,12BXSB were treated with CTX and prednisone as the control group.Peripheral blood stem cells of doner mouse(C57BL/6)after mobilizing with G-CSF were infused into recipients after pretreatment.Hematopoietic and immune reconstitution after transplantation were measured by blood cell analysis and flowcytometry.Recipients' renal pathological changes were measured with direct immunofluorescence after transplantation,proteinuria and anti-dsDNA antibody were also determined.Complications and mortality were compared between the two groups.Recipients'genetic map was analysed with PCR.Results Recipients'complete chimerism was observed after60days of transplantation.The lowest value of WBC declined to0.2?0.1?10 9 /L in Allo-HSCT group.The duration of WBC increased from the lowest value up to1.0?10 9 /L was47.5?12.8d in Allo-HSCT group.Early immune reconstitution could not be found in Allo-HSCT group.After transplantation reduction of proteinuria occurred in95.5%BXSB,anti-ds-DNA antibody turned to negative in54.5%BXSB,decrease of kindey immunofluorescence in90.9%BXSB,there was a significant difference between the two groups.There was no significant difference in the incidences of complication of bleeding,pneumonia and mortality between the Allo-HSCT group and the control group.Conclusions Allo-HSCT is an effective treatment method for lupus mice.It may be helpful in improving proteinuria and anti-dsDNA antibody and renal pathological changes of lupus mice.But the incidences of complication and mortality related to transplantation in Allo-HSCT group are higher than those in control group,so the value of Allo-HSCT in the treatment lupu mice has to be further studied.

Influence of Fludarabine on lupus activity of BXSB mice / 中国免疫学杂志

Objective:To investigate influence of Fludarabine to lupus activity of lupus mice and the effectiveness and safety of Fludarabine on the treatment of BXSB lupus mice and their possible methanism Methods:Fludarabine of 30 mg/(m 2?d) was injected into BXSB by tail vein,3 days continuously Results of treatment was observed through counting number of peripheral blood WBC Anti ds DNA and anti nuclear antibody in BXSB serum was measured by ELISA Pathologic transformation of kidney or urine protein was measured by immunofluorescence or urine protein test paper after treated by Fludarabine Expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte were measured by flowcytometry Results:The number of peripheral blood WBC of BXSB mice began to decline from the third day after treated by Fludarabine The lowest value 〔0 5?0 2)?10 9 L -1 〕of the number of peripheral blood WBC appeared on the seventh day and on the nineteenth day the number of peripheral blood WBC was up to 1 0?10 9 L -1 after treated by Fludarabine The falling of anti ds DNA and anti nuclear antibody in BXSB serum appeared on the fourteenth and twentieth one day after treated by Fludarabine, respectively Reduction of from +～++ turning?kindey immunofluorescence were 72 7% in group of Fludarabine Reduction of protein urine from ++～+++ turning ?～ - appeared on the twentieth one and twentieth eight days Reduction of expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte was obvious after treated by Fludarabine Conclusion:Fludarabine can evidently reduce the serum level of anti ds DNA and anti nuclear antibody of BXSB and reduce injury of kidney and formation of protein urine So Fludarabine may have good curative effect to severe SLE Fludarabine can reduce expression of CD4 +Fas +?CD8 +Fas +?CD45RO + Fas + on T lymphocyte,which may be one of methanism of Fludarabine to SLE