Dong Zheng

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (32)43.63 Total impact

  • Xiuzhen Tong · Juan Li · Zhenhai Zhou · Dong Zheng · Junru Liu · Chang Su ·

    Leukemia and Lymphoma 11/2014; 56(6):1-11. DOI:10.3109/10428194.2014.986477 · 2.89 Impact Factor
  • B Huang · J Li · X Xu · D Zheng · Z Zhou · J Liu ·
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    ABSTRACT: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with renal light chain (AL) amyloidosis. Twelve newly diagnosed patients with renal AL amyloidosis were treated with a combination of bortezomib (1.3mg/m(2)/d iv, d1, 4, 8, 11) and dexamethasone (20mg/d iv drip, d1-4). Median follow-up time was 22.5months (range, 2.1-53.6). Ten patients were evaluable. Five out of 10 (50%) patients achieved complete hematologic responses (CHR), and totally 8/10 (80%) achieved hematologic responses (HR). Median time to hematologic response was 1month. All patients who received HR had no hematologic progression during follow-up period. Five patients (50%) had kidney responses and the other 5 patients (50%) were stable. Median time to kidney response was 3months. No patients presented renal progression during follow-up. One patient achieved PR after 4 cycles of VD and then received autologous peripheral blood stem cell transplantation. Two out of 10 evaluable patients without hematologic response had died with median overall survival of 8.2months. Eight of them who had HR were alive with median follow-up time of 28.5months. Infection (6/12) and fatigue (5/12) were the most frequent side effects. Three patients developed herpes zoster and had to discontinue therapy. VD produces rapid, deep and durable hematological responses and renal responses in the majority of patients with newly diagnosed renal AL. It is well tolerated. This treatment may be a good option as first-line treatment for renal AL amyloidosis patients. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Pathologie Biologie 11/2014; 63(1). DOI:10.1016/j.patbio.2014.10.001 · 1.20 Impact Factor
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    ABSTRACT: To evaluate the short-term and long-term effect of novel agents followed by autologous hematopoietic stem cell (ASCT) in Chinese multiple myeloma(MM) patients in order to find out the optimal therapeutic regimen for transplant-eligible patients. Clinical data of 100 active MM patients receiving bortezomib-based induction regimens followed by high-dose melphalan and ASCT were retrospectively analyzed from June 1, 2006 to January 30, 2014. The overall response rates(ORR) after induction therapy, transplantation and consolidation and maintenance therapy were respectively 90.0%, 97.0%, and 98.9%. The median progress free survival(PFS) was 42.3 months. The median overall survival(OS) was not reached. The cumulative near complete response (nCR)+complete respanse(CR) rate was no longer improved after 4 cycles of induction therapy for non-light chain type MM and two cycles for light-chain type. In newly-diagnosed light-chain type MM patients, the cumulative nCR+CR rate after 4 cycles of bortezomib plus dexamethasone (VD) regimen was similar to that of bortezomib, doxorubicin and dexamethasone (PAD). While for those non-light-chain types, three drug-based regimen was better than two drug-based. PFS of patients receiving early ASCT was longer than that of late ASCT (50.7 months vs 26.6 months, P = 0.023) . PFS in patients receiving autologous bone marrow stem cell transplantation (ABMSCT) was longer than that of autologous peripheral blood stem cell transplantation (APBSCT) (NA vs 36.1 months, P = 0.049) . Maintenance therapy was beneficial regardless of the response rate after ASCT. Patients with CR at any time during the therapy had longer PFS than those with nCR. Bortezomib-based therapy followed by ASCT is the first line therapy for transplant-eligible MM patients. Patients with different types of M protein require different induction regimens. Maintenance is beneficial to patients after ASCT, no matter whether a CR is reached or not. Patients with CR after induction or ASCT tend to have longer survival.
    Zhonghua nei ke za zhi [Chinese journal of internal medicine] 11/2014; 53(11):865-72.
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    Juan Li · Ying Li · Beihui Huang · Dong Zheng · Mei Chen · Zhenhai Zhou ·
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    ABSTRACT: Bortezomib is effective in the therapy of multiple myeloma (MM), but causes infections that are different from those associated with conventional chemotherapy. It is important to identify the risk factors that facilitate infections associated with bortezomib therapy. In the present report, we sought to (1) define the features of the infections associated with this therapy and (2) identify the immune mechanisms responsible for the observed susceptibility to these infections. We first retrospectively analyzed the clinical data of 143 patients who had received bortezomib therapy for MM. We then prospectively assessed the modulation of T lymphocyte status during this therapy, and evaluated potential relationships between infections and T lymphocyte changes. The infection rates peaked during the first cycle of bortezomib therapy (47.6 %) in patients with MM (p < 0.05 vs. subsequent cycles). Bortezomib therapy was associated with higher incidence rates of viral and fungal infections (15.8 %, p < 0.05 vs. conventional chemotherapy). In addition, patients with the IgG immunophenotype showed higher bacterial and viral infection rates (respectively, p = 0.008 and 0.009). The T lymphocyte numbers significantly decreased after bortezomib therapy (p < 0.05), and the same was true for the Th1/Th2 ratio (p < 0.01). Patients with MM who have decreased lymphocyte counts, while on bortezomib therapy are more likely to develop bacterial or viral infections. In addition, an imbalance in T lymphocyte subsets is also associated with bacterial or viral infections in these patients.
    Cell Biochemistry and Biophysics 10/2014; 71(1). DOI:10.1007/s12013-014-0224-x · 1.68 Impact Factor
  • Juan Li · Beihui Huang · Ying Li · Dong Zheng · Zhenhai Zhou · Junru Liu ·
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    ABSTRACT: Abstract In order to investigate HBV reactivation and survival in MM patients receiving bortezomib-containing regimens, we analyzed 139 MM patients receiving bortezomib-containing regimens in our hospital. 27/139 patients were HBsAg+ with 9 of them having DNA levels > 500IU/ml including 4 > 1000 IU/ml. All but 5 HBsAg+ patients were treated with lamivudine or entecavir before chemotherapy until at least 6 months after chemotherapy or ASCT. HBV reactivation occurred in 6 HBsAg+ patients and 2 HBsAg- patients, including 6 who received an ASCT. OS and PFS of HBsAg- patients were significantly longer than HBsAg+ patients (both P values < 0.01). In view of these results, we confirmed that incidence of HBV reactivation was notable in MM patients receiving bortezomib-containing regimens, especially those underwent ASCT. HBsAg+ MM patients had poorer prognosis than HBsAg- patients. Prophylactic treatment should be prescribed to all HBsAg+ MM patients for a minimal duration of 12 months.
    Leukemia and Lymphoma 08/2014; 56(6):1-27. DOI:10.3109/10428194.2014.941833 · 2.89 Impact Factor
  • Juan Li · Han Ma · Xiuzhen Tong · Chang Su · Dong Zheng · Mei Chen · Chun Lu ·
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    ABSTRACT: Mantel cell lymphoma is one of the small B-cell non-Hodgkin's lymphomas and usually involves lymph nodes, bone marrow, spleen, liver, gastrointestinal tract, and Waldeyer's ring, but rarely skin and orbit. A 53-year-old man presented skin nodules and plaques on the head, trunk, and lower extremities for half a month, and the left periorbital region swelled 4 days ago. Serum calcium and lactate dehydrogenase were increased to 3.12 mmol/L (normal 2.03–2.65 mmol/L) and 853 U/L (normal 71–231 U/L), respectively. Histopathologic examination of the skin nodule revealed tumor cells infiltrated nodular distribution in the dermis and subcutaneous tissue. Immunophenotyping of the abnormal lymphocytes indicated positive reactions for L26, CD79a, Bcl-2, Cyclin D1, and Ki-67 (>80%), but negative for CD5, CD21, CD23, CD38, CD3, CD10, UCHL-1, TdT, MPO, CD30, ALK, CD117, and CD34. Fluorescence in situ hybridization analysis with the CCND1/IGH probe revealed a fusion signal on the abnormal lymphocytes. The final diagnosis was a rare case of blastoid mantle cell lymphoma involving skin and orbit with hypercalcemia. Following the R-Hyper-CVAD treatment plan, the patient achieved a quick and excellent recovery on the 6th day. Unfortunately, the patient eventually died of pneumonia one month later.
    Dermatologica Sinica 06/2013; 31(2):98–101. DOI:10.1016/j.dsi.2012.08.006 · 0.88 Impact Factor
  • Bo Lu · Juan Li · Jingxuan Pan · Beihui Huang · Junru Liu · Dong Zheng ·
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    ABSTRACT: Bendamustine is a bifunctional alkylating agent with some efficacy in the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Everolimus, an mammalian target of rapamycin (mTOR) inhibitor, is an additional promising chemotherapeutic agent that has efficacy in a variety of cancers. We investigated the individual and combinational cytotoxic effects of these drugs in MM cell lines (RPMI8226 and MM1.S) and primary MM cells. Our results demonstrated a synergistic effect of these drugs, which was effective for both p53-wild-type and p-53-deleted MM cells, but was minimal in mononuclear cells from a healthy donor. Combination treatment with the two agents inhibited proliferation and promoted cytotoxicity and apoptosis as assessed by Annexin-V/PI staining, caspase-3 degradation, and PARP cleavage. Cell death was associated with the up-regulation of the pro-apoptotic protein Bax and the down-regulation of the anti-apoptotic proteins Mcl-1 and survivin. The combination drug treatment also promoted a decrease in the levels of the downstream target proteins of the mTOR pathway, p70s6k, and 4EBP-1, as well as an increase in the level of phosphorylation of the tumor suppressor protein p53 in MM1.S cells. p21 was also down-regulated upon treatment with the two drugs, suggesting a mechanism of sensitization through the release of cell cycle arrest. Our results demonstrate a network of regulatory factors that may contribute to the synergistic cytotoxicity of everolimus and bendamustine, and provide a rationale for application for the combinatorial treatment of MM with alkylating agents and mTOR inhibitors in future clinical practice.
    Acta Biochimica et Biophysica Sinica 05/2013; 45(8). DOI:10.1093/abbs/gmt054 · 2.19 Impact Factor
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    ABSTRACT: In our study, we determined the efficacy of bortezomib-based induction therapy followed by autologous stem cell transplant (ASCT) in newly diagnosed and relapsed/refractory (R/R) multiple myeloma (MM) patients and compared the advantages of early versus late transplant. We used a retrospective analysis to examine 62 patients, including 46 cases of newly diagnosed MM (early transplant group) and 16 cases of relapsed/refractory MM (late transplant group). All of these patients received bortezomib-based induction therapy followed by ASCT. The efficacy and side effects of the treatment regimen were analyzed. Patients' overall survival (OS) and progression-free survival (PFS) times were determined. The ratio of complete remission to near-complete remission (CR/nCR) was 69.5% versus 56.2% (P=0.361), respectively, for the early transplant group versus the late transplant group, respectively, after receiving bortezomib-based induction therapy; the overall response rates of the two group were 91.3% and 81.2%, respectively (P=0.369). After receiving ASCT, the CR/nCR of the two groups increased to 84.8% and 81.3%, respectively. The median time required for neutrophil engraftment of the early transplant group and the late transplant group was 11 and 14.5 days, respectively (P=0.003); the median time required for platelet engraftment was 13 and 21.5 days (P=0.031), respectively. There were no significant differences in the toxic side effects observed during induction therapy and ASCT between the two groups. The OS of the two groups was not statistically different (P=0.058). The PFS of the early transplant group and the late transplant group was 41.6 and 26.5 months, respectively (P=0.008). Multivariate analysis demonstrated that the time of receiving ASCT, the types of M protein, and the International Staging System (ISS) stage were all independent factors that influenced PFS. In conclusion, patients in a suitable condition for ASCT should be recommended to have an early ASCT immediately after diagnosis.
    Chinese Journal of Cancer Research 04/2013; 25(2):166-174. DOI:10.3978/j.issn.1000-9604.2013.02.02 · 1.94 Impact Factor
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    ABSTRACT: Objective: To study the humoral immunity reconstitution and its relationship with infection in patients with multiple myeloma (MM) after undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). Methods: Forty-two MM patients undergoing auto-HSCT were included in this study. Peripheral blood were obtained for immunoglobulin detection, including IgG, IgA and IgM before transplantation and 1, 3, 6, 12, 18 and 24 months after transplantation. The time, type, pathogen of infection between 1 and 24 month after transplantation were analyzed. Results: The level of IgA at 6 month [(0.75±0.59) g/L] after auto-HSCT was lower than that of pre-auto-HSCT [(1.04±0.70) g/L], and reached the level of pre-auto-HSCT at 9 months [(0.99±0.52) g/L] after auto-HSCT. The level of IgM reached the level of pre-auto-HSCT [(0.45±0.26) g/L] at 3 months after auto-ASCT [(0.50±0.26) g/L]. The level of IgG reached the level of pre-auto-HSCT [(9.80±2.98) g/L] at 1 month after auto-HSCT [(11.09±2.69) g/L], and higher than that of pre-auto-HSCT at 9 months after auto-HSCT [(12.07±3.57) g/L]. The level of IgG with IgG-type MM was higher than that of patients with light-chain type and IgD-type MM at 6, 9 and 12 months after auto-HSCT. The IgA level of patients who obtained complete remission (CR) is much higher than that of patients who obtained nCR in IgG-type patients. The incidence of infection in 6 month after auto-HSCT was higher than that of (6-12) month and >12 month after auto-HSCT. The incidence of infection was strongly negative correlated with IgA (r =-0.943, P=0.005) and IgG (r=-0.943, P=0.005) level. The frequency of viral infection was also negatively correlated with IgA and IgG. Conclusion: The reconstitution time of IgG, IgA and IgM was different in MM patients after auto-HSCT. IgG recovered first, then IgM, and IgM the last. The incidence of infection was negatively correlated with IgA and IgG. With the recovery of IgG and IgA, the incidence of infection was decreased accordingly.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 04/2013; 34(4):317-22. DOI:10.3760/cma.j.issn.0253-2727.2013.04.015
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    ABSTRACT: Objective: To study the clinical significance of abnormal protein bands (APB) in multiple myeloma (MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation (ASCT). Methods: Sixty-eight MM patients submitted to bortezomib-based induction therapy and ASCT from January 2007 to July 2012 were retrospectively studied. Monoclonal protein was detected by immunofixation electrophoresis (IFE). Results: Of all 68 patients, 33 (48.5%) patients had APB. At the first emergence of an APB, two patients with light chain type achieved CR and before transplantation, and thirty-one patients were after transplantation with median time of 104 (ranged 33-404) days. The median duration of APB appearance was 105 (ranged 35-801) days. Patients who developed APB compared with those without APB, had a significantly higher CR plus very good partial response (VGPR) rates (100.0% vs 85.7%%, P=0.017) and CR rates (87.9% vs 62.9%) (P=0.03). There were no significant differences in gender, age, HGB, ALB, β2-microglobulin, M protein type, Durie-Salmon and ISS stages, the case number of first line or second line treatment, induction courses of bortezomib-based regimen, and the mode of ASCT. With a median follow-up of 33.4 (ranged 7.0-71.7) months, patients with APB tended to have a longer overall survival (OS) versus non-APB patients, although no significant difference obtained (P>0.05). Among APB patients, OS was longer in patients whose appearance of APB occurred <6 months after transplantation than those ≥ 6 months, but the significant difference was not obtained yet (P>0.05). Conclusions: Patients who developed APB had a significantly better response to bortezomib-based induction regimen followed ASCT. APB emergence has a good prognostic significance.
    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 04/2013; 34(4):327-31. DOI:10.3760/cma.j.issn.0253-2727.2013.04.017
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    ABSTRACT: The purposes of this study were to evaluate the infection by hepatitis B virus (HBV) and its impact on survival and to provide a clinical reference for monitoring and treating HBV during and after autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A retrospective analysis of HBV infections was performed in 70 MM patients who received a sequential bortezomib-containing induction therapy and ASCT in our department from June 2006 to February 2012. Among the 70 patients in our study, 11 cases (15.7 %) were hepatitis B surface antigen positive (HBsAg+), and 23 cases (33.3 %) were hepatitis B core antibody positive (HBcAb+). Eight cases were HBsAg, hepatitis B e antibody (HBeAb), and HBcAb positive, while one case was HBsAg, hepatitis B e antigen (HBeAg), and HBcAb positive. The median follow-up times for the HBsAg+ group and the HBsAg-negative (HBsAg-) group were 27.0 (7.6-85.2) months and 28.7 (7.1-111.0) months, respectively. The 1-year, 2-year, and 3-year overall survival rates of the HBsAg+ group were 90.9, 80.8, and 34.6 %, respectively, and the median survival time was 31.2 months (95 % CI, 24.8-37.6). The 1-year, 2-year, and 3-year overall survival rates of the HBsAg- group were 98.2, 94, and 84.6 %, respectively, while the median survival time was not yet available. There was a statistically significant difference (p = 0.008) in the overall survival rate between the two groups. By Cox regression analysis, we found that the HBsAg+ status was a prognostic factor, which could independently influence the overall survival rate for ASCT. In conclusion, the HBsAg+ status is an independent risk factor for patients with MM receiving ASCT. The application of standard antiviral treatment might help to overcome this risk factor.
    Tumor Biology 02/2013; 34(3). DOI:10.1007/s13277-013-0709-z · 3.61 Impact Factor
  • Dong Zheng · Juan Li · Bei-Hui Huang · Jun-Ru Liu · Wai-Yi Zou · Chang Su ·
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    ABSTRACT: Whether the sequential treatment with bortezomib plus dexamethasone (BD) followed by autologous hematopoietic stem cell transplantation (ASCT) could extend the overall survival period in multiple myeloma patients is still not clear. Few large case studies about this therapeutics in multiple myeloma were reported in China. Our purpose was to assess the efficacy and adverse effects of sequential treatment with BD chemotherapy and ASCT in patients with multiple myeloma. Fifty-three patients with newly diagnosed or relapsed/refractory multiple myeloma received BD as induction therapy before ASCT. Stem-cell mobilization was undertaken with cyclophosphamide 3 - 5 g/m(2) plus granulocyte colony-stimulating factor 300 µg/d. Target yield was 2.0×10(6) CD34(+) cells/kg. Conditioning for ASCT consisted of melphalan 200 mg/m(2). Thalidomide and/or a-interferon was used as post-transplantation maintenance treatment. The BD chemotherapy before transplantation was effective in 86.7% of the 53 patients, including 22.6% with complete remission (CR), 39.6% with near complete remission (nCR), and 24.5% with partial remission (PR). The best effect was achieved after two treatment courses. Most bortezomib-related adverse effects were classes 1 - 2. All patients were successfully mobilized after BD for autologous peripheral blood stem cell transplantation. The ASCT was effective in 96.3% of patients, including 49.1% with CR, 32.1% with nCR, and 15.1% with PR. The CR rate was significantly increased (49.1% vs. 22.6%, P < 0.05) by sequential ASCT. Within 27 (range, 6 - 53) months of follow-up, the efficacy of ASCT was maintained in 29 patients and further enhanced by post-transplantation maintenance treatment in four patients. Eleven patients died after transplantation. Among the patients undergoing BD/ASCT treatment, overall survival (OS) was significantly better in newly diagnosed patients in comparison to relapsed/refractory patients (P = 0.046). BD chemotherapy can be used as an induction therapy prior to ASCT in patients with multiple myeloma. Its rate of effectiveness is high and it alleviates symptoms quickly without affecting peripheral blood stem cell collection. The majority of adverse effects are mild (tolerable). Sequential BD with ASCT is the preferred option for transplant patients. First-line ASCT could prolong survival of newly diagnosed patients rather than delayed ASCT.
    Chinese medical journal 12/2012; 125(24):4454-9. DOI:10.3760/cma.j.issn.0366-6999.2012.24.024 · 1.05 Impact Factor
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    ABSTRACT: Background Splenectomy is the most effective treatment for patients with primary immune thrombocytopenia (ITP) who fail to respond to steroid therapy. Thus far, there is no effective means to predict the long-term haematological response of the procedure. The purpose of this study was to identify serum biomarkers as predictors of long-term response based on a proteomics approach. Methods The serum samples of ITP patients were collected before splenectomy and seven days after surgery. After depletion of the abundant serum proteins, pooled preoperative serum samples from four responders to splenectomy, four nonresponders and four healthy controls were subjected to two-dimensional gel electrophoresis (2-DE). Nine protein spots with at least a five-fold alteration in expression between responders and nonresponders were all identified as haptoglobin (Hp) by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometer (MS) analysis. The validation of serum Hp expression was performed using enzyme-linked immunosorbent assays (ELISA) in thirty-seven responders, thirteen nonresponders and twenty-one healthy controls. Results The preoperative serum levels of Hp in the nonresponders (925.9 ± 293.5 μg/ml) were significantly lower than those in the responders (1417.4 ± 315.0 μg/ml, p <0.001) and the healthy controls (1409.1 ± 354.2 μg/ml, p <0.001), while there was no significant difference between the latter two groups. The postoperative serum levels of Hp in responders and nonresponders were (1414.1 ± 225.0 μg/ml) and (952.9 ± 202.4 μg/ml), respectively. There were no significant differences between the serum Hp levels before and after surgery in both responders and nonresponders (p>0.05). The preoperative serum levels of Hp did not significantly correlate with preoperative platelet count of the same blood samples (r = 0.244, p = 0.087), while it positively correlated with postoperative peak platelet count (r = 0.622, p < 0.001). The optimal cutoff value of preoperative serum Hp levels (1173.80 μg/ml) derived from the receiver operating characteristic (ROC) curve led to 78.4% sensitivity and 84.6% specificity. Conclusions These results suggest that serum Hp levels may serve as a favourable predictor for the long-term response to splenectomy in ITP and may help to understand the pathophysiological differences between responders and nonresponders.
    Journal of Translational Medicine 10/2012; 10(1):208. DOI:10.1186/1479-5876-10-208 · 3.93 Impact Factor
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    ABSTRACT: This study was purposed to investigate the B cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) levels in bone marrow, and the BAFF receptor expression level on B cells in multiple myeloma (MM) patients, in order to explore the characteristics of B cells in bone marrow of MM patients. MM patients were studied before treatment (newly diagnosed group, 19 patients) and after treatment with improvement (stable group, 17 patients), 10 non-hematologic patients were selected as control (control group). The BAFF receptors (BAFF-R) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) on B cell (CD19(+)), naive B cell (CD19(+)IgD(+)) and memory B cell (CD19(+)CD27(+)) of bone marrow in all groups were detected by flow cytometry. The BAFF, APRIL level in bone marrow supernatant were tested with ELISA. The results showed that the BAFF-R expression level on CD19(+) cells in newly diagnosed group were higher than that in stable group and control group; there was no significant difference between the BAFF-R expression level on CD19(+)IgD(+) cells in newely diagnosed group and stable group, but BAFF-R expression level on CD19(+)IgD(+) cells in newely diagnosed group was higher than that in control group; the BAFF-R expression level on CD19(+)CD27(+) cells in newely group was higher than that in stable group and control group; there was no significant difference between the BAFF-R expression level on CD19(+) cells, CD19(+)IgD(+) cells or CD19(+)CD27(+) cells in stable group and control group. There was no significant difference among the TACI expression level on CD19(+) cells, CD19(+)IgD(+) cells or CD19(+)CD27(+) cells in newly diagnosed group, stable group and control group. The bone marrow supernatant BAFF level in newely diagnosed group was higher than that in stable group and control group, but there was no significant difference between stable group and control group. There was no significant difference among the bone marrow TACI levels in newly diagnosed group, stable group and control group. It is concluded that both the bone marrow BAFF level and the BAFF-R expression level on CD19(+) cell, CD19(+)IgD(+) cells and CD19(+)CD27(+) cells in MM patients increase, which may help to stimulate B cells, thereby may relate with to MM pathogenesis.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 10/2012; 20(5):1131-4.
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    ABSTRACT: To investigate the efficacy and safety of bortezomib-based induction regimen followed by autologous hematopoietic stem cell transplantation (ASCT) in pationts with multiple myeloma (MM). A retrospective analysis was performed upon clinical data of 62 MM patients who received bortezomib-based induction regimen followed by ASCT from June 2006 to June 2011. All patients were followed up to September 30, 2011. Overall response rate [complete remission (CR) + near complete remission (nCR) + partial remission (PR)], ≥ nCR rate (CR/nCR) and CR rate of post-induction with bortezomib-based regimen were 88.7%, 66.1% and 24.2%, respectively. After ASCT, CR rate and CR/nCR rate were increased to 50.0% and 82.3%, respectively, with significant differences (P = 0.003 and P = 0.032). The median time of neutrophil and platelet engraftment was 12.0 (9 - 43) days and 13.5 (0 - 120) days, respectively. Significances were found in neutrophil and platelet engraftment between MM patients with and without prior exposure to alkylating agents. Furthermore, engraftment of neutrophil and platelet in patients receiving peripheral blood stem cell transplantation were faster than those receiving bone marrow transplantation. No unexpected side effects occurred. The median time of follow-up was 26.5 (7-61) months. The median overall survival (OS) was not reached and the median progression-free survival (PFS) was 30 months. There were significant differences in OS and PFS between patients obtaining CR/nCR and those with ≤ PR before ASCT. Bortezomib-based induction regimen can improve the efficacy of ASCT in MM patients. The side effects are tolerant. Higher response quality before ASCT can translate to high rates of OS and PFS following high-dose therapy and stem cell transplantation.
    Zhonghua nei ke za zhi [Chinese journal of internal medicine] 04/2012; 51(4):279-83.
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    ABSTRACT: It is of clinical importance to find methods to overcome bortezomib resistance. In the current study, we clarified the relationship between resistance to bortezomib and the differentiation status of myeloma cells, and explored the feasibility of induction of differentiation in overcoming bortezomib resistance in myeloma. Cell morphology, immunoglobulin light-chain protein secretion levels, and XBP-1 expression were used to evaluate the differentiation status of myeloma cells. Low dose 2-ME2 alone or in combination with ATRA was used to induce differentiation in myeloma cells. The differentiation status of myeloma cells was related to myeloma sensitivity to bortezomib. After successful induction of differentiation, the myeloma cells were more sensitive to bortezomib with decreased growth and an increased rate of apoptosis. Induction of differentiation increased the proteasome workload in myeloma cells by increasing immunoglobulin secretion, while reducing proteasome capacity by decreasing proteasome activity. The imbalance between increased proteasome workload and decreased proteasome capacity is a possible mechanism by which induction of differentiation overcomes myeloma resistance to bortezomib. The current study demonstrated, for the first time, that myeloma differentiation status is associated with myeloma sensitivity to bortezomib and that induction of differentiation can overcome myeloma resistance to bortezomib.
    Biochemical and Biophysical Research Communications 03/2012; 420(3):644-50. DOI:10.1016/j.bbrc.2012.03.056 · 2.30 Impact Factor
  • Juan Li · Jia-hui Cai · Bei-hui Huang · Jun-ru Liu · Dong Zheng ·
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    ABSTRACT: To explore the efficacies and toxicities in multiple myeloma (MM) patients on the maintenance therapies of thalidomide and interferon-α so as to seek the optimal chemotherapeutic regimen. A retrospective analysis was conducted for 57 MM patients on the maintenance therapies of thalidomide and interferon-α after introduction and consolidation. And 56 MM patients without maintenance therapy were enrolled as the control group. The values of progression-free survival (PFS) and overall survival (OS) were significantly longer in the maintenance group and this translated into an improved estimated 3-year PFS of 75.4% (71.8%, 83.3%) versus 23.2% in the control group (P < 0.01). The estimated 4-year OS was higher in the maintenance group [89.5% (89.7%, 88.9%) vs 33.9%, P < 0.01]. No statistically significant differences existed among different maintenance groups in terms of PFS and OS. The administration of maintenance therapy extended both PFS and OS for MM patients of various M-proteins (P < 0.05). However, in the thalidomide group, PFS and OS were extended only in MM of immunoglobulin G (IgG) and immunoglobulin A (IgA) but not in light-chain patients. Furthermore, the MM patients of Durie-Salmon (DS) stages II and III and international staging system (ISS) stages II and III extended PFS and OS through maintenance (P < 0.05). While in those of ISS stage I, the differences were insignificant in terms of PFS and OS between two groups. The results were similar between the thalidomide and control groups. The patients achieving a partial remission (PR) or higher response level benefited from the maintenance therapy in terms of PFS and OS (P < 0.05). In the thalidomide group, the patients with below PR prolonged OS (P = 0.031) but did not achieve a longer PFS (P = 0.091). Both PFS and OS were extended through maintenance therapy after either stem cell transplantation or consolidation chemotherapies (P < 0.05). There was no significant difference in terms of PFS and OS between MM patients without maintenance therapy after transplantation and those without transplantation. The adverse effects of thalidomide, milder than those of interferon-α, could be tolerated in most patients. The incidence and severity of adverse effects showed no significant difference between the combination maintenance and single agent therapies. The maintenance therapies of thalidomide and interferon-α could improve the profiles of PFS and OS in MM patients. And there was no significant difference between them in terms of PFS and OS. However, the maintenance therapy of thalidomide is a better option due to its convenient application, milder adverse effects, reasonable cost and better efficacies in MM patients not achieving PR or receiving induction therapy without bortezomib or without transplantation.
    Zhonghua yi xue za zhi 12/2011; 91(48):3417-20. DOI:10.3760/cma.j.issn.0376-2491.2011.48.009
  • Beihui Huang · Juan Li · Zhenhai Zhou · Dong Zheng · Junru Liu · Mei Chen ·
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    ABSTRACT: The aim of the present study was to verify the potential association between multiple myeloma (MM) and hepatitis B/C virus (HBV/HCV) infection. This retrospective case-control trial included 299 patients with MM and 299 patients with acute leukemia (AL). Age and sex were matched between the two groups. The hepatitis B surface antigen (HBsAg) positivity rate was significantly higher in the MM group (19.4% vs. 12.0% in patients with AL; p = 0.014). The rate of HCV infection did not differ between the two groups. The incidence of cirrhosis was significantly higher in HBsAg+ patients (17.2% vs. 6.2% in HBsAg- patients; p = 0.011). The rate of hepatitis E virus (HEV) infection was also significantly higher in HBsAg+ patients (5.2% vs. 0.4% in HBsAg- patients; p = 0.025). Hepatic damage was much more common in HBsAg+ patients than in HBsAg- patients both prior to (22.4% vs. 8.7%; p = 0.006) and during chemotherapy for MM (67.2% vs. 28.6%; p < 0.001). ISS stage, HBsAg+, the use of bortezomib and thalidomide and autologous stem cell transplant were significant factors for overall survival in univariate analysis. In the Cox regression analysis, ISS stage (p = 0.027), HBsAg+ (p = 0.042) and the use of thalidomide (p = 0.001) showed a significant effect on the OS of these patients. The prevalence of HBV infection is higher in patients with MM than in subjects with other hematological malignancies such as AL. Hepatic injury is more common in patients with MM with HBV infection, particularly during chemotherapeutic treatment. HBsAg positivity may be a prognosis factor in patients with MM in HBV endemic areas.
    Leukemia & lymphoma 08/2011; 53(2):270-4. DOI:10.3109/10428194.2011.610013 · 2.89 Impact Factor
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    ABSTRACT: High anatomic location, fragility, and generous blood supply of the spleen makes laparoscopic splenectomy (LS) difficult to master, and few patients need splenectomy for benign disorders. The aim of this research was to assess operative outcomes and hematological results of a large series of patients treated with LS for chronic immune thrombocytopenic purpura (ITP) and to determine which clinical variables predict favorable hematological outcome. LS was successfully performed for 154 patients with chronic ITP from September 1999 to April 2009 at the First Affiliated Hospital of Sun Yat-sen University. Operative outcomes were assessed retrospectively. Long-term follow-up data were obtained from outpatient medical records and phone interviews. Clinical and laboratory variables (including gender, age, disease duration before surgery, previous response to steroids, preoperative platelet count, and postoperative peak platelet count) were evaluated by univariate analysis to identify potential predictors of hematological outcome. Multivariate Logistic regression model was used to determine independent predictors of hematological outcome. One patient died from subphrenic abscess and postoperative sepsis. The overall major morbidity rate was 8.4%. None of the patients required a second surgery for complications. Of the 127 patients available for a mean follow-up of 43.6 months (range 9 - 114 months), the overall initial response (i.e., at two months after LS) and long-term response to LS were achieved in 89.0% and 80.3%, respectively. Five patients (3.9%) developed pneumonia 3 - 35 months after LS. Univariate analysis showed a significant difference in mean age between responders (29.1 years) and nonresponders (38.8 years; P < 0.05). Patients who responded to steroid therapy had better hematological outcome than those who did not respond (P < 0.05). Compared to nonresponders, responders to LS had a significantly higher postoperative peak platelet count (404 × 10(9)/L versus 213 × 10(9)/L, P < 0.001). Multivariate Logistic regression analysis identified postoperative peak platelet count as the only independent predictor of favorable response to LS (P < 0.001). LS is a safe and effective treatment for chronic ITP. Postoperative peak platelet count may serve as a major predictor of long-term response.
    Chinese medical journal 04/2011; 124(8):1175-80. DOI:10.3760/cma.j.issn.0366-6999.2011.08.009 · 1.05 Impact Factor
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    ABSTRACT: To explore the clinical features of infection in multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (ASCT). Thirty-seven patients with MM undergoing ASCT were retrospectively analyzed for type and time of infection, pathogen, and outcome. Fifty-nine cases of infectious complications occurred in 33 patients (89.2%) after ASCT, with 34 cases (57.6%) of bacterial infections in 30 patients, 15 cases (25.4%) of fungal infections in 12 patients, 4 cases (6.8%) of cytomegalovirus (CMV) infection, 3 cases (5.1%) of herpes zoster virus infection and 3 cases (5.1%) of HBV reactivation. The proportion of bacterial infection, fungal infection and virus infection were 62.8%, 28.6% and 8.6% respectively in the early stage after ASCT, and 50.0%, 20.8% and 29.3% respectively in the median stage. Response to first-line antibiotic therapy was seen in 38 cases (64.4%). Infection-related mortality was 8.1% (3 cases). The incidence of infection in MM patients undergoing ASCT is high and they are susceptible to all pathogens. It is important to choose the right antifungal agents as quickly as possible to reduce infection-related mortality.
    Zhonghua nei ke za zhi [Chinese journal of internal medicine] 01/2011; 50(1):44-7.