Decreased Prognostic Value of International Prognostic Score in Chinese Advanced Hodgkin Lymphoma Patients Treated in the Contemporary Era / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The International Prognostic Score (IPS) was developed based on the data of Western advanced Hodgkin lymphoma (HL) patients treated before 1992. Only a few studies ever evaluated the application value of IPS in Chinese population or in patients treated in the contemporary era whose outcomes has improved significantly than before.</p><p><b>METHODS</b>We conducted a retrospective study involving 208 previously untreated Chinese advanced HL patients, who were admitted to Cancer Hospital Chinese Academy of Medical Sciences from January 1, 1999 to April 30, 2015 and received uniform first-line treatment. The prognostic value of both IPS and the seven IPS factors for freedom-from progression (FFP) and overall survival (OS) was assessed in this population. The statistical methods included Kaplan-Meier methodology, log-rank testing, and Cox proportional hazard regression analysis.</p><p><b>RESULTS</b>With a median follow-up time of 79 months (range, 15-210 months), the 5-year FFP and OS were 78.8% and 86.0% respectively, which improved obviously compared with the original IPS study. The IPS remained prognostic for both FFP (P = 0.041) and OS (P = 0.013), but the range narrowed obviously, with 5-year FFP ranging from 87.2% to 61.5%, 5-year OS ranging from 94.1% to 69.2%, and the separation of survival curves was not as good as before. Only two of the seven IPS factors showed a significant independent prognostic value in the multivariate analysis: Stage IV (for FFP, hazard ratio [HR] = 2.219, 95% confidence interval [CI]: 1.148-3.948, P = 0.016; for OS, HR = 2.491, 95% CI: 1.159-5.355, P = 0.019) and hemoglobin <105 g/L (for FFP, HR = 2.136, 95% CI: 1.123-4.060, P = 0.021; for OS, HR = 2.345, 95% CI: 1.099-5.042, P = 0.028). A simple prognostic score calculated by adding one point each for any of the two factors was prognostic both for FFP (P < 0.001) and OS (P < 0.001) with the survival curves separating very well, but the range still narrowed.</p><p><b>CONCLUSIONS</b>The IPS has decreased the prognostic value in Chinese advanced HL patients treated in the contemporary era. More prognostic factors are needed to supplement this original scoring system so as to identify different risk populations more accurately.</p>

Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma.</p><p><b>METHODS</b>From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis.</p><p><b>RESULTS</b>The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 10 6 CD34 + cells/kg and 68% had at least 5 × 10 6 CD34 + cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively.</p><p><b>CONCLUSION</b>ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.</p>

Comparative analysis of liver function in HBsAg-/HBcAb+ patients with diffuse large B-cell lymphoma treated with CHOP and R-CHOP regimens / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the liver function in patients with diffuse large B-cell lymphoma(DLBCL), who are hepatitis B surface antigen negative/antibody to hepatitis B core antigen positive (HBsAg-/HBcAb+), treated with CHOP and R-CHOP regimens.</p><p><b>METHODS</b>In this retrospective study, 86 DLBCL patients, who were HBsAg-/HBcAb+, were collected from Cancer Hospital of Chinese Academy of Medical Sciences between January 2005 and December 2008. The patients were given at least two cycles of chemotherapy using CHOP-like or R-CHOP-like regimen without anti-HBV treatment, and followed-up for at least 12 months after completion of therapy.</p><p><b>RESULTS</b>Forty-seven patients received CHOP-like regimen while 39 patients received R-CHOP-like regimen. There were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group after the 1st, 2nd, 3rd, 4th and 6th cycles (22.7% - 46.7% with CHOP and 17.6% - 34.2% with R-CHOP, respectively, (all P > 0.05), except for the 5th cycles (28.6% vs. 6.2%, P = 0.026). Liver function in most patients in CHOP group and R-CHOP group was normal after every cycle (53.3% - 77.3% and 65.8%-93.8%, respectively). Meanwhile, there were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group in the 1st-3rd month, 4th-6th month, 7th-9th month and 10th-12th month after completion of therapy (7.7% - 40.0% with CHOP and 7.4% - 32.0% with R-CHOP, respectively, all P > 0.05).</p><p><b>CONCLUSIONS</b>The present study reveals a low incidence of liver dysfunction in HBsAg-/HBcAb+ DLBCL patients, both in CHOP group and in R-CHOP group. It may indicate a potential low incidence of HBV reactivation in these groups, and Rituximab do not increase the rate of liver dysfunction. Therefore, these data may not support regularly prophylactic antiviral therapy during chemotherapy, but close monitoring of liver function, HBV serum markers and HBV DNA level are demanded.</p>

Evaluation of the role of rhIL-11 on hematological recovery in lymphoma patients after autologous hematopoietic stem cell transplantation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of recombinant human interleukin 11 (rhIL-11) on hematological recovery after autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma.</p><p><b>METHODS</b>A retrospective study was carried out on 73 patients with lymphoma after AHSCT. The patients were divided into two groups. The study group (n = 35) received rhIL-11 1.5 mg daily from the fifth day after AHSCT to the day when platelets recovering to 80.0×10⁹/L. The control group (n = 38) did not receive rhIL-11 after AHSCT.</p><p><b>RESULTS</b>All the 73 patients finished AHSCT from Mar 2003 to Dec 2008 in our department. Thirty-five patients received rhIL-11 and 38 patients did not. In the rhIL-11 group and control group, the nadir of platelet was (18.9 ± 5.0)×10⁹/L and (21.5 ± 6.0)×10⁹/L, respectively, with a significant difference (P = 0.04). The median time of platelet recovering to 50.0×10⁹/L was (14.3 ± 5.5) d and (13.2 ± 4.5) d (P = 0.37) in the two groups. There was no significant difference (P = 0.82) in the median numbers of platelet transfusion in the two groups. The curves of the mean of daily absolute platelet counts of the two groups were similar (P = 0.22). Adverse events related to rhIL-11 were not found in the rhIL-11 group.</p><p><b>CONCLUSION</b>The results of this study do not show obviously accelerating effect of rhIL-11 on the platelet recovery in lymphoma patients after AHSCT and obvious increase of adverse events after rhIL-11 administration.</p>

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma / 癌症

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center / 癌症

Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1-167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.

Primary subcutaneous panniculitis-like T-cell cutaneous lymphoma: clinical presentation, treatment and prognosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the clinical presentation, treatment and prognosis study of primary subcutaneous panniculitis-like T-cell cutaneous lymphoma (SCPTCL).</p><p><b>METHODS</b>Ten cases of SCPTCL, treated in our hospital from January 1999 to January 2009, were included in this study. Their clinicopathological data were reviewed and analyzed retrospectively.</p><p><b>RESULTS</b>the median age was 50.5 years (range: 10 - 58), 4 males and 6 females. There were seven CD56 positive, two negative cases and 1 unclear case. Four cases had repeatedly nodules regressed spontaneously without treatment before diagnosis and new nodules appeared at different sites. Seven patients presented with multiple subcutaneous nodules or deeply seated plaques, most commonly on the extremities and trunk. Ulceration of nodules occurred in 3 cases, and the lesions were painful in five cases. The lesions appeared nodules at the beginning, and then gradually grew into tumors. Four patients had abnormal liver function and one patient had hemophagocytic syndrome (HPS), four patients had lymphadenopathy or visceral involvement. Three cases with single lesion underwent surgical excision in combination with chemotherapy or chemotherapy/radiotherapy. One case lost follow up, and two cases live without disease. Among the seven patients with multiple lesions, lymphadenopathy or visceral involvement, one underwent local surgical excision and is alive without disease, six of them received chemotherapy or multi-modality treatment mainly with chemotherapy. Three of these 6 cases are alive without progression, one used histone deacetylase inhibitors after progression and obtained partial regression, and 2 died. The median follow-up for all the 10 patients was 44 months (range: 14 - 99). The progression free survival was 66.7% (6/9), and overall survival was 77.8% (7/9).</p><p><b>CONCLUSION</b>SPTCL has an indolent course, some lesions can regress spontaneously and relapse again. Patients with single lesion may live long-term without disease after multimodality therapy. Patients with multiple lesions or extracutaneous involvement are sensitive to CHOP-like regimen, but the duration of remission is short. Histone deacetylase inhibitors may be a promising drug in the treatment for SCPTCL relapse.</p>

Clinical features and prognostic factors of angioimmunoblastic T cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the clinical features and prognostic factors of patients with angioimmunoblastic T-cell lymphoma (AITL).</p><p><b>METHODS</b>The clinicopathological and follow-up data of 18 AITL patients undergoing integrated treatment from Feb. 1998 to April 2009 in our department were retrospectively analyzed. All of the patients received CHOP-like regimens as initial chemotherapy, including 4 once treated with radiotherapy and 1 with high dose therapy followed by autologous stem cell transplantation (HDT-ASCT) as upfront consolidation therapy. B-cell, T-cell and NK-cell subgroup proportions in the peripheral blood were tested by flow cytometry in 6 patients.</p><p><b>RESULTS</b>The median age of the 18 patients was 55 years, male and female ratio was 2.6:1. Seventy-two percent of the patients were in an advanced stage. 72% of them had B symptoms, 69% hypergammaglobulinemia, 60% elevated LDH and 47% anemia. Forty-four percent achieved CR after initial treatment with CHOP-like regimens. With the median follow-up of 26 months, the overall 2-year survival and disease free survival (DFS) rates were 62.2% and 44.4%, respectively. In the univariate analysis, only age > 30 years and primary refractory disease adversely affected overall survival (OS); age > 30 years, advanced stage, B symptoms and splenomegaly adversely affected DFS. Four patients suffered from severe pneumonia during treatment, 2 of them died of respiratory failure. Flow cytometry of peripheral blood lymphocytes showed that 5 of the 6 tested cases had decreasing proportion of CD3(+)CD4(+) T cells, B cells and NK cells but elevated CD3(+)CD8(+) T cells. Two heavily treated patients achieved partial and complete response by thalidomide therapy, with a progression free survival (PFS) of 2 and 6+ months, respectively.</p><p><b>CONCLUSION</b>AITL patients do not response well to CHOP-like regimens chemotherapy. Age < 30 years and sensitive to initial chemotherapy are associated with prolonged OS. Effectiveness of thalidomide in the treatment of AITL deserves further investigation. Peripheral blood lymphocytes test indicates that AITL patients suffered from both natural and acquired immune defects.</p>

Comparison of the efficiency of CHOP-based regimen with or without high dose consolidation treatment combined with hematopoietic stem cell transplantation in 63 lymphoblastic lymphoma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively analyze and compare the treatment efficiency of CHOP-based regimens with or without high-dose consolidation treatment combined with hematopoietic stem cell transplantation (HDT-HSCT) in the patients with lymphoblastic lymphoma (LBL).</p><p><b>METHODS</b>From 1989 to 2004, totally 63 patients with LBL were initially treated with a standard CHOP-based regimen. Forty-two of the 63 patients achieved complete response (CR), 26 of those subsequently received consolidation HDT-HSCT, while the other 16 had 6-8 cycles of standard CHOP-based treatment only.</p><p><b>RESULTS</b>Of the 63 patients, 57 had a T-LBL and 6 B-LBL, with a median age of 20 years, 19 (30.2%) had a stage I-II diseases and 44 (69.8%) stage III-IV diseases, 61.9% presented with a mediastinal mass. Bone marrow involvement presented in 28.6% of the patients. Fourteen percent had central nervous system involvement. The median follow-up period was 24 months, and the estimated 5-year overall survival and disease-free survival of this series was 31.2% and 29.3%, respectively. Of the 42 patients who achieved CR, the 5-year OS rate of the patients who received HDT-HSCT as a consolidation therapy was 59.8% versus 14.6% of the patients treated by CHOP-based regimens alone (P=0.004). Bone marrow involvement, age > or =20 years, short response duration and primary refractory disease were factors significantly associated with poor outcome. Among the 18 patients with bone marrow involvement, 3 received allogeneic HSCT and were all still alive at the follow up time of 22, 32 and 37 months, respectively, while another 4 received auto-HSCT and all died of the disease within 14 months.</p><p><b>CONCLUSION</b>Short term treatment with a CHOP-based regimen is not sufficient for the patients with lymphoblastic lymphoma. High-dose consolidation treatment and hematopoietic stem cell transplantation may improve overall survival and disease free survival. Bone marrow involvement, age >20 years, and short response duration and primary refractory disease are all the factors significantly associated with poor outcome. For the patients with bone marrow involvement, allohematopoietic stem cell transplantation is superior to auto-hematopoietic stem cell transplantation.</p>

Gene construction, expression and activities analysis of human leptin / 生物工程学报

Six 89bp primers were designed on the base of the cDNA sequence encoding the human leptin reported on the NCBI. The synthetic gene with 464bp encoding rhLep was obtained by SOE ( splicing by overlap extension) PCR. The expression vector pET22b(+)/rhLep was constructed and transformed into E. coli BL21 (DE3). The rhLep protein was expressed as inclusion bodies with the yield of more than 50% of total bacterial proteins after IPTG induction. The rhLep protein, which has a molecular weight about 16kD, was purified by Ni2+ affinity chromatography column and identified by SDS-PAGE. The MTT Assay shows that rhLep promotes EC304 cells growth at the low concentration of 10ng/mL to 30 ng/mL, and rhLep appears cytotoxic to EC304 cells with the high dose of 50ng/mL to 225ng/mL. The viability of EC304 cells decreases to 1.2% with the concentration of 225ng/mL of rhLep. The massive apoptosis of rhLep on EC304 cells is observed by AO-staining under fluorescent microscope. All these results would lay the foundation for the further study of its biological functions in vitro and in vivo.

Mobilization of autologous peripheral blood stem cells with etoposide and recombinant human granulocyte colony stimulating factor in malignant tumor patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the combined effect of etoposide (Vp-16) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) on mobilization of autologous peripheral blood stem cells (APBSC) in malignant tumor patients and find out the suitable dose of Vp-16.</p><p><b>METHODS</b>Thirty patients were randomly divided into two groups, 15 in each group. In group A, Vp-16 1000 mg/m(2) was injected intravenously in six divided doses, for 2 hours every 12 hours on day 1, 2 and 3. In group B, Vp-16 1500 mg/m(2) was injected intravenously in six divided doses for 3 hours every 12 hours on day 1, 2 and 3. rhG-CSF was given as a single daily injection subcutaneously at the dose of 300 microg.body(-1).day(-1) from the day of the nadir of white blood cell (WBC) to the day before the end of APBCS harvest. APBSC harvest started when WBC > or = 5.0 x 10(9)/L and finished when accumulated mononuclear cells (MNC) > or = 5 x 10(8)/kg or CD34+ cells > or = 2 x 10(6)/kg.</p><p><b>RESULTS</b>There was no significant difference between the time of nadir, nadir of WBC, absolute neutrophil count (ANC), the beginning time and continuous time of rhG-CSF given, the beginning time and continuous time of APBSC harvest. When the blood volume, flow rate and continuous time of apheresis were similar in each apheresis in the two groups, the number of APBSC in each harvest and total number of APBSC were also not significantly different between the two groups. The side effects induced by Vp-16 were also not significant different between the two groups.</p><p><b>CONCLUSION</b>Vp-16 combined with rhG-CSF is a safe and highly effective method for APBSC mobilization, 1000 mg/m(2) and 1500 mg/m(2) of Vp-16 possess similar efficiency and side effects for APBSC mobilization.</p>

Clinical and pathological features of 23 patients with primary lymphoma of the testis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the clinical and pathological features of primary lymphoma of the testis and try to find out the rational treatment modality.</p><p><b>METHODS</b>Retrospective and follow-up analysis was conducted in 23 patients with primary lymphoma of the testis. Survival analysis was performed by Kaplan-Meier process.</p><p><b>RESULTS</b>The primary clinical symptom was painless tumefaction. 78.3% lesions were Stage I(E) on diagnosis. Most of them were intermediate grade B cell lymphoma. All patients received orchiectomy followed by chemotherapy and some followed by radiotherapy. The median survival time was 42 months. The overall survival rates at 1, 3 and 5 years were 100.0%, 59.8% and 36.5%, respectively. The disease-free survival rates at 1, 3 and 5 years were 66.7%, 42.3% and 36.3%, respectively.</p><p><b>CONCLUSION</b>Primary lymphoma of the testis is preferably treated by multi-modality treatment. More than 6 cycles of chemotherapy is rational after orchiectomy. Regional radiotherapy tends to reduce the local relapse.</p>