Low-dose pegylated recombinant human granulocyte-colony stimulating factor as hematopoietic support for adjuvant chemotherapy in Chinese patients with breast cancer: An open-label, randomized, non-inferiority trial.

AIMS: The recommended dosage of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) for Western chemotherapy patients is 6 mg per cycle. However, for Eastern Asians, the optimal dose remains unknown. METHODS: This open-label, randomized, non-inferiority trial (NCT05283616) enrolled Chinese female breast cancer patients receiving adjuvant chemotherapy. Participants were randomized to receive either 3 or 6 mg of PEG-rhG-CSF per cycle, stratified by body weight (BW; ≤60 kg vs. >60 kg). The primary endpoint was timely absolute neutrophil count (ANC) recovery before the second cycle of chemotherapy. RESULTS: A total of 122 patients were randomized and 116 were included for efficacy analyses. The timely ANC recovery rate in the 3 mg arm was 89.8%, compared to 93.0% in the 6 mg arm (one-sided 95% confidence interval [CI] lower limit for difference: -11.7%), meeting the prespecified non-inferiority margin of 15%. The rate was 93.3% with PEG-rhG-CSF 3 mg and 96.6% with 6 mg in patients with BW ≤ 60 kg, and 86.2% and 89.3%, respectively, in those with BW > 60 kg. Although the incidence of severe neutropenia was similar across arms, the occurrence of excessively high ANC and white blood cell counts was higher in the 6 mg arm. No grade ≥3 adverse events related to PEG-rhG-CSF occurred. CONCLUSION: Three milligrams of PEG-rhG-CSF per cycle provided non-inferior neutrophil protection and attenuated neutrophil overshoot compared to 6 mg doses. This low-dose regimen could be a new supportive care option for Chinese breast cancer patients receiving anthracycline-based adjuvant chemotherapy.

Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

Treatment and prognosis of newly diagnosed advanced-stage extranodal natural killer / T cell lymphoma: a single-center real-world study across two decades.

INTRODUCTION: Although there is now a consensus on asparaginase-based chemotherapy regimens in treatment of advanced-stage extranodal natural killer / T cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified. METHODS: Newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations. RESULTS: The study included 83 newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase- compared to non-asparaginase-based regimens significantly prolonged PFS (P=0.007; HR=0.48, P=0.020) and showed a tendency to improve OS (P=0.064; HR=0.74, P=0.359). Gemcitabine-based regimens also exhibited a trend towards improved PFS (P=0.048; HR=0.59, P=0.164) and OS (P=0.008; HR=0.67, P=0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (P=0.020; HR=0.40, P=0.022) and slightly better OS (P=0.054; HR=0.79, P=0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (P=0.051) and OS (P=0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months. CONCLUSION: Asparaginase and gemcitabine alone brought favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs.

Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.

Decreased Prognostic Value of International Prognostic Score in Chinese Advanced Hodgkin Lymphoma Patients Treated in the Contemporary Era.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases.

BACKGROUND: To evaluate the antitumor activity and toxicity of icotinib as initial treatment in lung adenocarcinoma patients with brain metastases. METHODS: Twenty-one patients with histologically or pathologically documented brain metastatic lung cancer were administered icotinib as initial treatment from 2011 to 2015 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Chemotherapy response was assessed by Response Evaluation Criteria in Solid Tumors and toxicity was evaluated according to National Cancer Institute-Common Toxicity Criteria. Icotinib was administered three times per day at a dose of 125mg. RESULTS: The median overall and progression-free survival rates were 15.2 (1.2-31.5 months, 95% confidence interval [CI] 6.6-23.7 months) and 8.9 months (0.6-30.5 months, 95% CI 3.4-14.3 months), respectively. The overall response and disease control rates were 61.9% and 90.5%, respectively. Icotinib was well tolerated, and no grade 3/4 adverse events were observed. The most common grade 1/2 adverse events included acneiform eruptions (38.1%), diarrhea (19.0%), and stomatitis (9.5%). CONCLUSION: Icotinib is effective and well tolerated as initial treatment in lung adenocarcinoma patients with brain metastases.

GDP (Gemcitabine, Dexamethasone, and Cisplatin) Is Highly Effective and Well-Tolerated for Newly Diagnosed Stage IV and Relapsed/Refractory Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

This study was conducted to evaluate the effectiveness and tolerance of GDP (gemcitabine, dexamethasone, and cisplatin) regimen in patients with newly diagnosed stage IV and relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).The study enrolled 41 ENKTL patients who received GDP regimen at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2008 and January 2015.The disease status was newly diagnosed stage IV in 15 patients and relapsed/refractory in 26 patients. The median number of cycles of chemotherapy per patient was 6 (range, 2-8 cycles). The overall response rate and complete-remission rate were 83.0% (34/41) and 41.5% (17/41), respectively. After a median follow-up of 16.2 months, 1-year progression-free survival rate and 1-year overall survival rate for the whole cohort were 54.5% and 72.7%. Grade 3 to 4 adverse events included neutropenia (34.1%), thrombocytopenia (19.5%), and anemia (14.6%).Our study has suggested high efficacy and low toxicity profile of GDP regimen in patients with newly diagnosed stage IV and relapsed/refractory ENKTL.

Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.

Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis.

Chemotherapy is the current mainstay of treatment for patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC), whereas the role of locoregional radiotherapy remains to be defined. In this study, we retrospectively evaluated the outcome of systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy (IMRT) as first-line treatment for these patients. Forty-one patients with pathologically confirmed NPC with distant metastasis at initial diagnosis seen between March 2005 and February 2014 were included. All the patients were treated with platinum-based systemic chemotherapy followed by definitive IMRT to the primary head and neck region with or without concurrent chemotherapy. In addition, local treatment to metastatic lesions was given in 19 patients. With a median follow-up time of 25 months, 24 patients had died, and the estimated median overall survival time was 31.2 months. The 1-, 2-, 3- and 5-year estimated OS rates were 89.9, 67.4, 41.1 and 22.5%, respectively. Prognostic analyses showed that serum lactate dehydrogenase level (P = 0.021) and number of metastatic sites (single vs. multiple; P = 0.016) were significant prognostic factors. Five patients are still alive without evidence of disease after 52 to >101 months. All of them had a single metastatic lesion and received local treatment to metastatic sites. These results suggest that the use of definitive IMRT to treat the locoregional tumor in combination with systemic chemotherapy may prolong survival in patients with newly diagnosed metastatic NPC, making curability a possible consideration in selected patients with single metastasis. Further prospective clinical trials are warranted.

Evaluation of the boson chemiluminescence immunoassay as a first-line screening test in the ECDC algorithm for syphilis serodiagnosis in a population with a high prevalence of syphilis.

We developed a new Boson chemiluminescence immunoassay (CIA) and evaluated its application with cross-sectional analyses. Our results indicated that the Boson CIA demonstrated strong discriminatory power in diagnosing syphilis and that it can be used as a first-line screening test for syphilis serodiagnosis using the European Centre for Disease Prevention and Control algorithm or as a confirmatory test when combined with a patient's clinical history.

Bcl-2/IgH expression of diffuse large B-cell lymphoma cells in minimal bone marrow infiltration.

BACKGROUND: We sought to investigate the role of the Bcl-2 translocation at the chromosomal and protein levels in minimal bone marrow (BM) infiltration by diffuse large B-cell lymphomas (DLBCL). METHODS: The presence of the Bcl-2/IgH fusion gene was detected in BM samples and paraffin-embedded lymph node (LN) samples from 103 patients with DLBCLs using FISH. Bcl-2 protein levels in BM and paraffin-embedded tissues were quantified using immunocytochemistry (ICC) and immunohistochemistry (IHC), respectively. RESULTS: Bcl-2/IgH translocation in paraffin-embedded LN tissue sections was observed in 43 (41.7%) patients by FISH. Of the 43 patients, the Bcl-2/IgH rearrangement in the bone marrow specimens occurred in 34 patients. The Bcl-2/IgH recombination rate in stage III cancers was not significantly different compared to the rate observed in stage I/II cancers (p = 0.101), respectively showing no statistical differences between stage IV and I/II (p = 0.179). In 64.7% (22/34) of the cases with t(14;18), Bcl-2 was detected based on ICC analysis. Positive Bcl-2 ICC staining and the t(14;18) translocation were positively correlated (p < 0.001). We then applied our FISH method to slides with at least one abnormal cell and were subjected to FISH analysis after staining. During the follow-up, no infiltration by cytomorphology for 16 DLBCL patients whose bone marrow presented Bcl-2/IgH gene rearrangement at diagnosis, and two cases were positive by morphology compared to FISH-positive results 6 months later; 9 out of 16 patients (56.3%) presented with positive Bcl-2/IgH results earlier than the morphology evaluation after 12 months. CONCLUSIONS: Utilizing both FISH and cytologic morphology, the assessment of Bcl-2/IgH translocation status could contribute to the better detection of minimal bone marrow infiltration and relapse receiving treatment by DLBCL cells.

High-dose therapy and autologous stem cell transplantation in peripheral T-cell lymphoma: treatment outcome and prognostic factor analysis.

Peripheral T-cell lymphoma (PTCL) carries a poor prognosis with conventional treatment. We retrospectively analyzed data from 45 patients with PTCL who received high-dose therapy and autologous stem cell transplantation (HDT/ASCT) from 1990 to 2008 in our center. Eighteen patients underwent HDT/ASCT in complete remission to induction chemotherapy (CR1), and 27 patients underwent HDT/ASCT in other disease statuses. The median follow-up was 113.5 months (range 52.6-261.0) for surviving patients. The 5-year overall survival (OS) and progression-free survival (PFS) were 64 and 60 %, respectively. The 5-year OS for patients in CR1 and in other disease statuses was 89 and 47 %, respectively (P = 0.002), and 5-year PFS was 83 and 43 % (P = 0.007). In the subgroup excluding anaplastic large cell lymphoma, patients transplanted in CR1 also had significantly better 5-year OS (82 vs. 37 %, P = 0.009) and PFS (82 vs. 33 %, P = 0.008) than those transplanted in other disease statuses. Multivariate analysis showed that CR1 status was the only significant prognostic factor for OS (P = 0.040) and PFS (P = 0.040). These results support the use of HDT/ASCT consolidation in CR1 for PTCL patients. Prospective randomized trials are necessary to confirm the efficacy of this approach.

Gemcitabine-based combination regimen in patients with peripheral T-cell lymphoma.

This study was conducted to evaluate the efficacy and safety of gemcitabine-based combination regimen in patients with peripheral T-cell lymphoma (PTCL). Between May 2007 and August 2011, 26 consecutive patients with PTCL were enrolled in this study. Of these 26 patients, histology was extranodal NK/T-cell lymphoma, nasal type in 14 (53.9 %), peripheral T-cell lymphoma, not otherwise specified in nine (34.6 %), anaplastic large cell lymphoma, ALK negative in three (11.5 %). The majority of patients had newly diagnosed (65.4 %) and advanced (80.8 %) diseases. Treatment regimen was DIMG (dexamethasone, ifosfamide, methotrexate, and gemcitabine) given to the first 6 patients, and GDP (gemcitabine, dexamethasone, and cisplatin) given to the remaining 20 patients. The median follow-up time was 25 (range 7-60) months. The overall response rate was 88.5 %. Twelve (46.2 %) patients achieved complete remission, 11 (42.3 %) patients achieved partial remission, and 1 (3.8 %) patient had stable disease (SD), two (7.7 %) patients had progressive diseases. The 1- and 2-year progression-free survival rates were 58.7 and 45.9 %, while 1- and 2-year overall survival rates for all patients were 80.6 and 63.7 %, respectively. Adverse events included grade 3 or 4 neutropenia (35.0 %) and thrombocytopenia (15.0 %) from patients treated with GDP. Grade 3 or 4 neutropenia and thrombocytopenia were 100.0 and 66.7 %, respectively, for patients who received DIMG regimen. Our study has demonstrated that the gemcitabine-based combination regimen, especially GDP regimen, is safe and well tolerated with promising clinical activity in patients with PTCLs.

[Evaluation of the role of rhIL-11 on hematological recovery in lymphoma patients after autologous hematopoietic stem cell transplantation].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

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.

[Comparative analysis of liver function in HBsAg-/HBcAb+ patients with diffuse large B-cell lymphoma treated with CHOP and R-CHOP regimens].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

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.

Bcl-2/IgH expression in minimal bone marrow infiltration by follicular lymphoma cells.

The purpose of this study was to investigate the roles of bcl-2 chromosomal translocation and Bcl-2 protein expression in follicular lymphoma (FL) minimal bone marrow (BM) infiltration. We identified the same bcl-2/IgH fusion gene in paraffin-embedded lymph node (LN) samples and BM samples using immunohistochemistry (IHC), immunocytochemistry (ICC), cytologic morphology and fluorescence in situ hybridization (FISH). The presence of the Bcl-2/IgH fusion gene in the BM samples and paraffin-embedded LN samples from 56 patients with follicular lymphomas was detected using FISH. The Bcl-2 protein levels in BM and paraffin-embedded tissues were quantified using ICC and IHC, respectively. Approximately 78.6% (44/56) of the paraffin­embedded LN tissue sections that underwent FISH analysis had a bcl-2/IgH translocation. The primary lesion was also positive for the bcl-2/IgH fusion gene, as were the BM minimal infiltrates. The bcl-2/IgH rearrangement occurred in 88.6% (39/44) of the BM specimens. The bcl-2/IgH recombination rate in stage III/IV cancers was significantly different to that observed in stage I/II cancers (p=0.041). In 59% (23/39) of the cases with t(14;18), Bcl-2 was found to be present as assessed by ICC. Positive Bcl-2 ICC staining and the t(14;18) translocation (as detected using FISH) were positively correlated (p=0.028). We then applied the FISH method to slides that had previously been morphologically evaluated using Wright-Giemsa staining; any slides with at least one abnormal cell were subjected to FISH analysis following staining. The assessment of bcl-2/IgH translocation status may contribute to the better detection of minimal BM infiltration by FL cells. Utilizing FISH and cytologic morphology techniques allows for earlier and more accessible BM examination.

Evaluation of a colloidal gold immunochromatography assay in the detection of Treponema pallidum specific IgM antibody in syphilis serofast reaction patients: a serologic marker for the relapse and infection of syphilis.

Syphilis remains as a worldwide public health problem; hence, it is necessary to develop a new diagnostic approach that is easier and faster than conventional tests. A new testing method to detect Treponema pallidum IgM (TP-IgM), named colloidal gold immunochromatography assay (GICA), is presented in place of fluorescent treponemal antibody absorption (FTA-Abs). TP-IgM was detected using GICA developed on syphilis-specific recombinant proteins TPN17 and TPN47. The FTA-Abs IgM test was set as the gold standard. A GICA TP-IgM test was performed to detect syphilis in 1208 patients who received recommended therapy for syphilis for more than 1 year at the Xiamen Center of Clinical Laboratory in China from June 2005 to May 2009. One hundred blood donors were set up as control. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 98.21%, 99.04%, 93.75%, 99.73%, 102.3, and 0.018, respectively. Detection on 500 interference specimens indicated that the biological false-positive rate of the GICA test was extremely low and was free from other biological and chemical factors. The patients were divided into the following experimental groups based on the results of toluidine red unheated serum test (TRUST) and treponemal pallidum particle agglutination (TPPA): (1) the syphilis serofast reaction (SSR) group consisted of 411 cases with (+) TRUST and (+) TPPA, which exhibited no clinical manifestations of syphilis after 1 year of recommended syphilis treatment; (2) the serum cure group, which was further subdivided into group A, a group that consisted of 251 cases with (-) TRUST and (+) TPPA, and (3) group B, a group that consisted of 546 cases with (-) TRUST and (-) TPPA; and (4) the blood donor control group, which consisted of 100 healthy persons with (-) ELISA-TP and (-) TPPA. We used the FTA-Abs method and the GICA method to detect TP-IgM; the positive rate of TP-IgM in 411 SSR patients was 34.55% and 36.01%, respectively. However, in serum cure group A, the positive rate of TP-IgM was 10.36% and 11.16%, respectively. The χ(2) test revealed that there is a significant difference in the positive rate between these 2 groups (P < 0.01). The TP-IgM positive rate in the same group, as detected by the GICA method and the FTA-Abs method, had no significant difference in statistics. However, as detected by the GICA method and the FTA-Abs method, all the samples in serum cure group B and the control group were negative for TP-IgM. The TP-IgM-positive result demonstrated that active T. pallidum remained in the bodies of SSR patients. In summary, the characteristics of GICA TP-IgM correspond to that of FTA-Abs TP-IgM; this can be used as a serologic marker for the relapse and infection of syphilis in place of the conventional FTA-Abs IgM test.

Development of a colloidal gold-immunochromatography assay to detect immunoglobulin G antibodies to Treponema pallidum with TPN17 and TPN47.

Syphilis remains a worldwide public health problem; it is necessary to develop a new diagnostic approach that is easier and faster than conventional tests. Here, we report a new testing method named colloidal gold-immunochromatography assay (GICA) to detect syphilis instead of fluorescent treponemal antibody-absorption (FTA-Abs). Syphilis-specific immunoglobulin G (IgG) antibody was detected with GICA established on syphilis-specific recombinant proteins, TPN17 and TPN47. FTA-Abs Treponema pallidum (TP)-IgG was set as the gold standard. A GICA test was performed to detect the serum of 14 967 subjects who took a serologic test for syphilis at the Xiamen Center of Clinical Laboratory, Fujian, China, from March 2009 to February 2010, among which 1326 cases were diagnosed as syphilitic. The results showed that the sensitivity, specificity, and positive predictive value were 99.38% (1279/1287), 99.96% (12,975/12,980), and 99.61% (1279/1284), respectively. The positive rate between the 2 test methods had no significant difference (χ(2) = 0.003, P > 0.05). Detection on 500 interference specimens indicated that the biologic false-positive rate of the GICA test was extremely low and free from other biologic and chemical factors. The characteristics of GICA TP-IgG correspond to that of FTA-Abs TP-IgG (EUROIMMUN Medizinische Labordiagnostika, Germany). The GICA test is convenient, fast, and inexpensive, and it can be used both as a confirmatory test and a screening indicator, instead of FTA-Abs TP-IgG.