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We aimed to assess the association between induction chemotherapy (CT) response and survivals and to explore an induction CT response-adapted treatment strategy for localized extranodal NK/T-cell lymphoma (NKTCL) receiving first-line sequential CT and radiation (RT).We retrospectively reviewed the data of patients with localized NKTCL receiving first-line CT+RT from 2010 to 2020 at two independent institutes (primary cohort,Patients with initial complete remission (CR) had higher final CR rate than the others (99.1% vs. 78.7%,Deep remission from induction CT was associated with favorable survivals in localized NKTCL receiving CT+RT, and an induction CT response-adapted individualized treatment strategy might be recommended in clinical practice.

Background The treatment outcomes and prognosis of lymphoma are affected by various factors such as hospital types. This study was to describe the temporal trend in the survival of lymphoma in an academic center in China. Methods A total of 3840 consecutive patients with lymphoma diagnosed between 1996 and 2015 were reviewed. Eighty patients were excluded, and finally, 3760 patients were analyzed in this study. The cohort was divided into four groups according to calendar periods at diagnosis: 1996‐2000, 2001‐2005, 2006‐2010, and 2010‐2015. The overall survival (OS) rates among the four groups were compared. Results The 5‐ and 10‐year OS for the whole cohort were 62% and 52%, respectively. The 5‐year OS of patient with classic Hodgkin lymphoma (cHL), mature B‐cell lymphoma (BCL), and peripheral T‐cell lymphoma (PTCL) were 79%, 63%, and 50%, respectively. Among mature BCL, the 5‐year OS was highest in follicular lymphoma (77.8%), followed by Burkitt lymphoma (76.5%), marginal zone lymphoma (74.1%), diffuse large B‐cell lymphoma (61.5%), small lymphocytic lymphoma/chronic lymphocytic leukemia (55.1%), and mantle cell lymphoma (44.3%). Among PTCL, the 5‐year OS was highest in ALK+anaplastic large cell lymphoma (79.0%), followed by ALK−anaplastic large cell lymphoma (63.1%), natural killer/T‐cell lymphoma (57.7%), angioimmunoblastic T‐cell lymphoma (34.9%, and peripheral T‐cell lymphoma not otherwise specified (27.6%). Significant improvement in the survival of lymphoma was observed, with the 5‐year OS increasing from 48% in 1996‐2000 to 65% in 2011‐2015 (P, Increase in overall survival of lymphoma from 1996 to 2015.

Background Extranodal natural killer (NK) cell/T-cell lymphoma (NKTCL), a rare type of non-Hodgkin's lymphoma, has strongly been associated with Epstein-Barr virus (EBV) infection. However, there are no EBV genomes isolated from NKTCL, and the roles the variations of EBV strains play in the pathogenesis of NKTCL are still unclear. Materials and Methods In this study, whole EBV genomes from eight primary NKTCL biopsy specimens were obtained using next-generation sequencing, designated NKTCL-EBV1 to NKTCL-EBV8. Results Compared with the six mostly referenced EBV strains, NKTCL-EBVs closely resemble the GD1 strain but still harbor 2,072 variations, including 1,938 substitutions, 58 insertions, and 76 deletions. The majority of nonsynonymous mutations were located in latent and tegument genes. Moreover, the results from phylogenetic analysis of whole NKTCL genomes and specific genes demonstrated that all the NKTCL-EBVs were related to Asian EBV strains. Based on the amino acid changes in certain residues of latent membrane protein 1 (LMP1) and EBV-determined nuclear antigen 1 (EBNA1), all the NKTCL-EBVs were sorted to China 1 and V-val subtype, respectively. Furthermore, changes in CD4+ and CD8+ T-cell epitopes of EBNA1 and LMP1 may affect the efficacy for a cytotoxic T lymphocyte (CTL)-based therapy. Conclusion This is the first large study to our knowledge to obtain EBV genomes isolated from NKTCL and show the diversity of EBV genomes in a whole genome level by phylogenetic analysis. Implications for Practice In this study, the full-length sequence of Epstein-Barr virus (EBV) isolated from eight patients with nasal natural killer/T-cell lymphoma (NKTCL) was determined and further compared with the sequences previously reported isolated from other malignancies. Phylogenetic analysis showed that NKTCL-EBV strains are close to other Asian subtypes instead of non-Asian ones, leading to the conclusion that EBV infections are more likely affected by different geographic regions rather than particular EBV-associated malignancies. Therefore, these data have implications for the development of effective prophylactic and therapeutic vaccine approaches targeting the personalized or geographic-specific EBV antigens in these aggressive diseases.

Background The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo. Methods NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry. Results CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7–21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients. Conclusions CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects. Trial registration The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421.

Background GLS-010 (zimberelimab) is a novel, fully human, anti-programmed death-1 monoclonal antibody that shows promising efficacy and safety in advanced solid tumors. This trial aimed to evaluate the efficacy and safety of GLS-010 (zimberelimab) in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r-cHL). Methods This phase II, single-arm, open-label, multicenter clinical trial was conducted at 24 centers in China and enrolled patients with r/r-cHL after two or more lines of therapy. The patients were administered intravenous GLS-010 (zimberelimab) (240 mg, once every 2 weeks) until progression, death, unacceptable toxicity, or consent withdrawal. The primary end-point was the objective response rate assessed by an independent radiology review committee (IRC). This study was registered (NCT03655483). Results Eighty-five patients were enrolled between August 2018 and August 2019. The median follow-up was 15.8 months. Seventy-seven patients (90.6%; 95% confidence interval [CI] 82.3–95.9) had an IRC-assessed objective response. The complete response rate was 32.9% (n = 28). The 12-month progression-free survival and overall survival rates were 78% (95% CI 67.5–85.6) and 99% (95% CI 91.9–99.8), respectively. Treatment-related adverse events (TRAEs) were observed in 92.9% of participants. Grade III or IV TRAEs occurred in 24 (28.2%) of the 85 participants. The most common grade III or IV TRAEs were abnormal hepatic function (5.9%), hyperuricemia (4.7%), decreased neutrophil count (3.5%), and increased weight (3.5%). Only one grade V AE, gastrointestinal infection, occurred. Conclusions GLS-010 (zimberelimab) appears to be effective and safe for the treatment of Chinese patients with r/r-cHL. Long-term follow-up is required to confirm these clinical benefits.

Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-020-01282-7.

The combination of chemotherapy and L-asparaginase (L-ASP) treatment significantly increased survival rate in an adult patient with extranodal natural killer (NK)/T-cell lymphoma (NKTCL). However, hypersensitivity reactions of L-ASP in some patients limited its application. Polyethylene glycol-conjugated asparaginase (PEG-ASP) has a lower immunogenicity and longer circulating half-life than unconjugated L-ASP, and has been reported to be effective and well-tolerated in children with acute lymphoblastic leukemia. Cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisolone (CHOP) is the most common chemotherapy for non-Hodgkin lymphoma. In this report, we sought to study the efficacy and safety of PEG-L- CHOP in NKTCL in adult Chinese patients. Our study is a prospective, multi-center, open-label clinical trial. Patients with newly diagnosed adult NKTCL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included six cycles of PEG-L-CHOP regimen. Radiotherapy was scheduled after 2–4 cycles of PEG-L-CHOP regimen, depending on the stage and primary anatomic site. We enrolled a total of 33 eligible patients. All 33 patients completed 170 cycles of chemotherapy combined with radical radiotherapy. The overall response rate was 96.9% (32/33) with 75.8% (25/33) achieving complete responses and 21.2% (7/33) achieving partial responses. The overall survival (OS) at 1, 2, 3-year were 100, 90.61 and 80.54%, respectively. The major adverse effects were bone marrow suppression, reduction of fibrinogen level, liver dysfunction, and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded. PEG-L-CHOP chemotherapy in combination radiotherapy is safe and durably effective treatment for adult extranodal NK/T-cell lymphoma with fewer allergic reactions. This study was approved by the Peking University Beijing Cancer Hospital Ethics Review Committee (reference number: 2011101104). The clinical trial registration number ChiCTR1800016940 was registered on July 07, 2018 at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ). The clinical trial was registered retrospectively.

Background: For peripheral T-cell lymphomas (PTCLs) patients, high-dose therapy combined with autologous peripheral blood stem cell transplantation (HDT/ASCT) has been an alternative treatment option, due to the lack of efficacy from conventional chemotherapy. While not all PTCLs could have benefit in survival from HDT/ASCT. The aim of this study was to evaluate the value of high-dose therapy combined with autologous peripheral blood stem cell transplantation (HDT/ASCT) in Chinese patients with Peripheral T-cell Lymphomas (PTCLs), in order to determine the cohort most suitable to receive HDT/ASCT. Methods: A total of 79 patients with PTCLs who received HDT/ASCT in Peking University Cancer Hospital & Institute from January 2001 to august 2016 were retrospectively analyzed. Results: At a median follow-up time of 23.6 months, the 2-year progression-free survival (PFS) and 2-year overall survival (OS) of the entire cohort were 75.2% and 83.6% respectively. Patients with first complete remission (CR1) (2-year PFS 85.8%, 2-year OS 94.2%) were superior to others in survival. Patients with second complete remission (CR2) had no advantage in survival compared with those with first partial remission (PR1) (2-year PFS: 43.8% vs. 76.2%, p=0.128; 2-year OS: 72.9% vs. 77.1%, p=0.842). In multivariate analysis, response before HDT/ASCT (p=0.001) and LDH before HDT/ASCT (p=0.047) were highly predictive for PFS, while no factors could independently predict OS. Subgroup analysis revealed that HDT/ASCT could improve the survival of patients with angioimmunoblastic T-cell lymphoma (AITL), especially in patients with chemosensitivity. Patients with natural killer / T-cell lymphoma (NKTCL) who received HDT/ASCT with CR1 also had benefit in survival from HDT/ASCT, while nearly 90% of non-CR1 patients appeared bone marrow involvement after HDT/ASCT. Conclusion: Patients who achieved complete remission after first-line therapy, especially with AITL and NKTCL, should strongly be recommended to receive HDT/ASCT. The future prospective trial is warranted.

Extranodal natural killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (HPS) (NK/T-LAHS) is a heterogeneous and life-threatening disease, which warrants investigation of its risk factors and clinical features. We retrospectively analyzed the clinical records of 202 patients with extranodal NK/T cell lymphoma and compared the characteristics and survival of extranodal NK/T cell lymphoma patients with and without HPS. The cumulative incidence of NK/T-LAHS was 11.4 % (23/202). In a multivariate logistic regression model, younger age (p = 0.012), bone marrow involvement (p = 0.012), and reduced serum albumin (p 0.001) were independent risk factors for developing HPS in patients with extranodal NK/T cell lymphoma. The survival of extranodal NK/T cell lymphoma patients was aggravated when complicated with HPS, with an overall 2-year survival of 72.1 and 30.4 %, respectively (p 0.001). Six patients with HPS onset at lymphoma diagnosis tended to have a poor performance status (p = 0.040), while the rate of elevated bilirubin was significantly higher in 17 patients with HPS onset at lymphoma relapse (p = 0.045). After HPS onset, treatment response was poor (response rate, 17.4 %) and survival was dismal with a median of 26 days. Univariate analysis showed that patients with lactate dehydrogenase1000 U/L (p = 0.048) and disseminated intravascular coagulation (p = 0.004) had shorter survival time. Extranodal NK/T cell lymphoma was frequently complicated with HPS, and survival was discouraging in this circumstance. Intensive chemotherapy regimens including L-asparaginase or pegaspargase and allogeneic stem cell transplantation should be investigated.

Background Oncologic immunotherapy is a form of therapy intended to reactivate the immune response to tumor cells using agents that modulate immune checkpoints, such as programmed cell death protein 1 and its ligand (PD-1/PD-L), and cytotoxic T-lymphocyte-associated antigen 4. Along with activation of the immune system to tumors, immune-mediated kidney side effects have been reported, most of which are cases of interstitial nephritis. Glomerular disease, however, appears rare. Case presentation Herein, we describe a patient with nephrotic syndrome related to treatment with an anti-PD1 antibody for Hodgkin lymphoma. Following the third dose of anti-PD1 antibody, the patient developed massive proteinuria and nephrotic syndrome. Kidney biopsy showed diffuse podocyte foot process effacement upon electron microscopy, which was consistent with minimal change disease. Corticosteroid treatment yielded full and rapid remission of nephrotic syndrome in 1 month. Conclusion The present case suggests an association between anti-PD1 therapeutic immune activation and the development of nephrotic syndrome. Given the increasing prevalence of oncologic immunotherapy, patients should be routinely monitored for kidney side effects associated with these agents.

// Lijuan Deng 1 , Yuqin Song 1 , Ken H. Young 2 , Shimin Hu 2 , Ning Ding 1 , Weiwei Song 1 , Xianghong Li 3 , Yunfei Shi 3 , Huiying Huang 1 , Weiping Liu 1 , Wen Zheng 1 , Xiaopei Wang 1 , Yan Xie 1 , Ningjing Lin 1 , Meifeng Tu 1 , Lingyan Ping 1 , Zhitao Ying 1 , Chen Zhang 1 , Yingli Sun 1 , Jun Zhu 1 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China 2 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China Correspondence to: Jun Zhu, e-mail: lymphoma2015@hotmail.com Keywords: hepatitis B virus, diffuse large B-cell lymphoma, hepatitis B surface antigen, B-cell receptor, complementarity determining region 3 Received: April 30, 2015 Accepted: July 09, 2015 Published: July 22, 2015 ABSTRACT While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known more than this epidemiologic evidence. We studied a cohort of 587 patients with DLBCL for HBV infection status, clinicopathologic features, and the immunoglobulin variable region in HBV surface antigen (HBsAg)-positive patients. Eighty-one (81/587, 13.8%) patients were HBsAg-positive. Compared with HBsAg-negative DLBCL, HBsAg-positive DLBCL displayed a younger median onset age (45 vs. 55 years), more frequent involvement of spleen or retroperitoneal lymph node (40.7% vs. 16.0% and 61.7% vs. 31.0% respectively, both p < 0.001), more advanced disease (stage III/IV: 76.5% vs 59.5%, p = 0.003), and significantly worse outcome (2-year overall survival: 47% versus 70%, p < 0.001). In HBsAg-positive DLBCL patients, almost all (45/47, 96%) amino acid sequences of heavy and light chain complementarity determining region 3 exhibited a high homology to antibodies specific for HBsAg, and the majority (45/50, 90%) of IgHV and IgLV genes were mutated. We conclude that 13.8% of DLBCL cases are HBV-associated in HBV-endemic China and show unique clinical features and poor outcomes. Furthermore, our study strongly suggests that HBV-associated DLBCL might arise from HBV antigen-selected B cells.

The introduction of rituximab has improved the overall prognosis of diffuse large B-cell lymphoma (DLBCL). However, the impact of rituximab on central nervous system (CNS) involvement in DLBCL remains a matter of debate. Patients with DLBCL and no CNS involvement at initial diagnosis were eligible for this analysis. Patients must have received treatment either with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP). We analyzed the incidence, clinical features and outcomes of CNS involvement that developed during or after completion of therapy. A cohort of 599 patients was eligible for this analysis. With a median follow-up of 26 and 21 months, respectively, 19 of 294 (6.5 %) in the CHOP group and 13 of 305 (4.3 %) in the R-CHOP group developed CNS involvement. Rituximab did not significantly reduce the risk of CNS involvement either in the univariate (P = 0.354) or in the multivariate analysis (RR 0.632, 95 % CI 0.301–1.327, P = 0.225). No patient developed CNS disease after 19 months in the R-CHOP group whereas four patients (21.1 %) in the CHOP group developed CNS disease 2 years after initial diagnosis (range 34–83 months). Systemic disease prior to or coincident with CNS occurrence was more common in the CHOP group than in the R-CHOP group (73.7 versus 38.5 %, P = 0.046). Isolated CNS events were more common in the R-CHOP group than those in the CHOP group (53.8 versus 10.5 %, P = 0.015). This study indicates that isolated CNS events are more common in DLBCL patients treated with R-CHOP than those treated with CHOP alone. Our data also suggest that the time and pattern of CNS events and systemic disease status differ with the addition of rituximab. Better methods for earlier detection and prophylaxis of CNS involvement are needed in the rituximab era.

To compare the prognostic value of different models in patients with early-stage diffuse large B-cell lymphoma (DLBCL).Early-stage DLBCL patients diagnosed from January 2000 to December 2012 were analyzed retrospectively. All patients received with at least 2 cycles of immunochemotherapy R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with or without radiotherapy. The prognostic value of international prognostic index (IPI) , revised IPI (R-IPI) and enhanced IPI (NCCN-IPI) was compared.Ninety-seven cases of early-stage DLBCL were included in the study. The median age was 58 years (15-88 years) with a median follow-up of 34.7 months (range 7.3-77.4 months). The expected 5-year overall survival (OS) for entire group was 82%. There was no patient in the high risk group according to IPI or NCCN-IPI. According to IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 95%, 38% and 60%, respectively. According to R-IPI, the 5-year OS in the very good, good, and poor risk groups were 93%, 75% and 60%, respectively. According to NCCN-IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 92%, 85% and 29%, respectively.NCCN-IPI would be of an ideal prognostic model for early-stage DLBCL patients.

Glioblastoma is universally fatal because of its propensity for rapid recurrence due to highly migratory tumor cells. Unraveling the genomic complexity that underlies this migratory characteristic could provide therapeutic targets that would greatly complement current surgical therapy. Using multiple high-resolution genomic screening methods, we identified a single locus, adherens junctional associated protein 1 (AJAP1) on chromosome 1p36 that is lost or epigenetically silenced in many glioblastomas. We found AJAP1 expression absent or reduced in 86% and 100% of primary glioblastoma tumors and cell lines, respectively, and the loss of expression correlates with AJAP1 methylation. Restoration of AJAP1 gene expression by transfection or demethylation agents results in decreased tumor cell migration in glioblastoma cell lines. This work shows the significant loss of expression of AJAP1 in glioblastoma and provides evidence of its role in the highly migratory characteristic of these tumors. Mol Cancer Res; 10(2); 208–17. ©2012 AACR.

The aim of this study was to evaluate the outcomes using the dose-adjusted Berlin–Frankfurt–Munster (BFM-90) regimen without radiotherapy in adolescents and adults with T cell lymphoblastic lymphoma (T-LBL) at Beijing Cancer Hospital. Between March 2004 and December 2013, 57 newly diagnosed T-LBL patients were treated in our center. We retrospectively analyzed their main clinical characteristics and prognosis. The media age of the patients at diagnosis was 26 (range 14–54). At a median follow-up of 24 months (range 5–119), 38 patients (67 %) were alive. The estimated 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 64 and 60 %, respectively. Abnormal WBC at diagnosis, high IPI and no early response were indicated as adverse prognostic factors for both PFS and OS (p

To analyze clinical features and outcomes of non-upper aerodigestive tract NK/T-cell lymphoma (NUAT-NKTCL).Clinical data of 44 patients with NUAT-NKTCL diagnosed at Peking University Cancer Hospital between 1999 and 2013 were retrospectively analyzed.Of the 44 patients, there were 31 males and 13 females with a median age of 39 years (range, 15 to 82 years). 27 patients (61.4%) were stage III/IV, 28(63.6%) with B symptoms, 12(27.3%) ECOG ≥ 2, 18 (40.9%) IPI score ≥ 3, and 48.8% patients had elevated serum lactate dehydrogenase. The common primary sites were skin (21/44, 47.2%) and intestinal tract (11/44, 25.0%). All the 44 patients received systemic chemotherapy. After a median follow-up of 13.5 months (range, 0.3-121.0 months), 32 patients died, and the median overall survival (OS) was 16 months with 1-year OS rate as 54.1%. CR rate of the 26 patients received CHOP or CHOPE regimens as the first line chemotherapy was 19.2% (5/26). Then L-asparaginase (L-ASP)- based regimens were used for salvage treatment, with CR rate of 47.7% and the median OS of 13 months. CR rate of the other 18 patients received L-ASP-based regimens in the firstline therapy was 55.6% (10/18) with the median OS of 16 months. Using L-ASP in firstline treatment obviously improved CR rate (P=0.015), but did not affect OS (P=0.774).Although L-ASP improved the efficacy of NUAT-NKTCL, but the prognosis remained dismal. Thus, more effective treatment strategies are required for NUAT-NKTCL.

To evaluate the value of flow cytometry (FCM) in the diagnosis of bone marrow involvement in patients with non-Hodgkin's lymphoma (NHL).The cytomorphology, biopsy and FCM tests were performed concurrently on bone marrow samples from 206 patients who were consecutively diagnosed as NHL from March 2013 to August 2013 at Peking University Cancer Hospital. The results were analyzed and compared.Totally bone marrow involvement occurred in 25.7% (53/206) patients. The detection positivity of bone marrow involvement by cytomorphology, biopsy and flow cytometry were 6/14, 6/14 and 9/14 respectively in 14 T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukemia (T-LBL/ALL) patients; 9.2% (14/152) , 19.1% (29/152) and 23.7% (36/152) respectively in 152 mature B-cell NHL patients; 0 (0/40) , 15.0% (6/40) and 2.5% (1/40) in 40 cases of mature T/NK-cell NHL. The overall rate of concordance of biopsy and flow cytometry was 88.3%.FCM has a high sensitivity in detecting bone marrow involvement in NHL patients, especially those with T-LBL/ALL and B-cell NHL. And a combination of morphology, biopsy and FCM may improve the sensitivity and accuracy in the detection of bone marrow involvement in NHL patients.

To explore the clinical features and treatments of mucosa-associated lymphoid tissue (MALT) lymphoma.The clinical data of 80 MALT lymphoma patients treated from September 2000 to November 2012 were retrospectively analyzed.Among them, 32 (40.0%) had gastric MALT lymphoma and 48(60.0%) non-gastric MALT lymphoma. Gastric lymphoma associated anemia accounted for 50.0% (16/32) (25.0% (12/48) in non-gastric group, P = 0.022). In non-gastric group, stage III-IV diseases accounted for 35.4% (17/48) (12.5% (4/32) in gastric group, P = 0.022). During a median follow-up of 30 months, the 5-year overall survival (OS) rate was 90.0% and 5-year progression-free survival (PFS) rate 67.0%. For the non-gastric group, surgery plus chemotherapy group was superior in PFS to surgery alone group (the 3-year PFS rate 83.0% and 33.0%; median PFS 43.4 months and 20.3 months) (P = 0.040). Five-year OS in patients on first-line rituximab and chemotherapy without rituximab were 100.0% and 86.0% respectively (P = 0.106). Short-term response (OR = 0.258, P = 0.020) and low albumin (OR = 3.967, P = 0.009) were independent factor for PFS.Non-gastric MALT lymphoma is easily disseminated. Systemic treatment may be considered for advanced non-gastric MALT lymphoma. Surgery often leaves residual lesions for gastric MALT lymphoma.

To determine the predictive value of interim and end-of-treatment ¹⁸F-FDG PET-CT after first-line treatment in patients with Hodgkin lymphoma (HL).The clinical data of 50 newly diagnosed HL patients were retrospectively analyzed. Baseline, interim and end-of-treatment PET-CT were performed, and then imaging results were analyzed for the survival of patients via software SPSS 13.0.Fifty patients received first-line treatment with ABVD (doxorubicin + bleomycin + vincristine + dacarbazine) or BEACOPP (bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine+ prednisone) regimen. Interim PET-CT of 35 patients were performed after 2-4 cycles of treatment, 46 patients received PET-CT scans at the end of treatment. After a median follow-up of 29.4 months (12.2-52.4 months), the 3-year progression-free survival (PFS) rates were 100% and 70% for the interim PET-CT negative (n=25) and positive (n=10) patients, respectively (P=0.004). The 3-year PFS rates were 100% and 60% for the post-treatment PET-CT negative (n=36) and positive (n=10) patients, respectively (P0.01).Interim and end-of-treatment PET-CT were correlated with 3-year PFS rates for HL patients. They may play an important role in predicting the outcome of HL. The relationship with OS can not be determined because of the short follow-up time.

Purpose To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T –cell lymphoma (ENKTL), we conducted a prospective phase II study of L-asparaginase, cyclophosphamide, vincristine, doxorubicin and dexamethasone (CHOP-L) regimen in combination with radiotherapy. Patients and methods Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included 6–8 cycles of CHOP-L (cyclophosphamide, 750 mg/m2 day 1; vincristine, 1.4 mg/m2 day 1 (maximal dose 2 mg), doxorubicin 50 mg/m2 day 1; dexamethasone 10 mg days 1–8; L-asparaginase 6000 u/m2 days 2–8). Radiotherapy was scheduled after 4–6 cycles of CHOP-L regimen, depending on stage and primary anatomic site. The primary endpoint was complete response (CR) rate. Results A total of 38 eligible patients were enrolled. The median age was 40.5 years (range, 15 to 71 years). Their clinical characteristics were male to female ratio, 24:14; Ann Arbor stage I, 20; II, 11; III, 3; IV, 4. CR and overall response rates were 81.6% (95% CI, 69.3% to 93.9%) and 84.2%, respectively. With a median follow-up of 25 months, the 2-year overall survival, progression-free survival and disease-free survival rates were 80.1% (95%CI, 73.3% to 86.9%), 81% (95%CI, 74.5% to 87.5%) and 93.6% (95%CI, 89.3% to 97.9%), respectively. The major adverse events were myelosuppression, liver dysfunction, and digestive tract toxicities. Grade 3 to 4 leukopenia and neutropenia were 76.3% and 84.2%, respectively. No treatment-related death was observed. Conclusion CHOP-L chemotherapy in combination with radiotherapy is a safe and highly effective treatment for newly diagnosed ENKTL.

Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: median survival after diagnosis is about 14 months. Established good prognostic factors are limited, but include young age, high Karnofsky Performance Status (KPS), high mini-mental status examination score, O6-methylguanine methyltransferase promoter methylation, and resection of98% of the tumor. Standard treatment includes resection, followed by concurrent chemotherapy and radiotherapy. GBM research is being conducted worldwide at a remarkable pace, with some of the more recent promising studies focused on identification of aberrant genetic events and signaling pathways, tumor stem cell identification and characterization, modulation of tumor immunological responses, combination therapies, and understanding of the rare long-term survivors. Past treatment strategies have failed for various reasons; however, newer strategies in trials today and on the horizon encourage optimism. To help illustrate 'where we have been' with this fatal disease and 'where we are going' with contemporary studies, we include in this review a detailed history of Phase III clinical trials for GBM, with a final emphasis on exciting new treatment strategies that offer hope for future GBM therapy.

Glioblastoma is the commonest primary brain tumor, as well as the deadliest. Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: survival after diagnosis is about 1 year. Established prognostic factors are limited, but include age, Karnofsky performance status, mini-mental status examination score, O6-methylguanine methyltransferase promoter methylation and extent of surgery. Standard treatment includes resection of > 95% of the tumor, followed by concurrent chemotherapy and radiotherapy. Nevertheless, GBM research is being conducted worldwide at a remarkable pace, in the laboratory and at the bedside, with some of the more recent promising studies focused on identification of aberrant genetic events and signaling pathways to develop molecular-based targeted therapies, tumor stem cell identification and characterization, modulation of tumor immunological responses and understanding of the rare long-term survivors. With this universally fatal disease, any small breakthrough will have a significant impact on survival and provide hope to the thousands of patients who receive this diagnosis annually. This review describes the epidemiology, clinical presentation, pathology and tumor immunology, with a focus on understanding the molecular biology that underlies the current targeted therapeutics being tested.

There is no standard salvage regimen for patients with refractory and relapsed extranodal NK/T-cell lymphoma (NKTCL), nasal type. This study was conduced to evaluate the efficacy of L-asparaginase-based regimen as a salvage regimen, on refractory and relapsed extranodal NKTCL, nasal type. Between March 1996 and March 2008, 45 patients with refractory and relapsed extranodal NKTCL, nasal type, were studied retrospectively. All patients were treated with L-asparaginase-based salvage regimen. Thirty-nine patients also received primary involved-field radiation after L-asparaginase-based chemotherapy. The complete response rate, partial response rate, and overall response rate for the whole group were 55.6%, 26.7%, and 82.2%, respectively. Both of 3-year and 5-year overall survival (OS) rates were 66.9%. The major adverse effects of L-asparaginase were myelosuppression, liver dysfunction, hyperglycemia, and allergic reaction. In general, the side effects could be tolerated. On univariate analysis, age, the stage of disease, and performance status were found to be prognostic factors influencing OS. On multivariate analysis, the stage of disease and age were independent prognostic factors for OS. L-Asparaginase-based regimen was obviously effective for the patients with refractory and relapsed extranodal NKTCL, nasal type.

Purpose Midline NK/T-cell lymphoma nasal-type is an aggressive neoplasm with poor prognosis in most instances. To improve the treatment outcome, we have tried using L-asparaginase based regimen as salvage regimen plus radiation in CHOP failures, and report here the therapeutic results and prognostic factors. Patients and methods From March 1992 to January 2005, 46 Chinese patients with midline NK/T-cell lymphoma nasal-type were initially treated with CHOP regimen as first-line chemotherapy. The patients who failed CHOP regimens were altered to receive L-asparaginase based salvage regimen. All the patients received primary involved-field radiation after chemotherapy. Results Thirteen patients (28.3%) sensitive to CHOP regimen received CHOP regimen for 6 cycles plus locoregional radiation, and achieved complete remission (CR). Thirty-three patients failed CHOP regimen were altered to received L-asparaginase-based salvage regimen for 2∼6 cycles (median 3 cycles) plus locoregional radiation, and seventeen of the 33 CHOP failures (51.5 %) (L-asparaginase group) reached CR. The CR rate for the whole group was 65.2% (30/46 cases). The 5-year overall survival (OS) rates were 64.5% for the whole group and 55.9% for L-asparaginase group, respectively. On univariate analysis, disease stage, fever symptom and performance status were significant factors influencing overall survival. On multivariate analysis, only disease stage and fever symptom remained as independently significant factors influencing OS. Conclusion In this preliminary study, the results indicated that L-asparaginase based regimen might be a promising new salvage chemotherapeutic regimen in CHOP failures and conduce to improve the treatment outcome in midline NK/T-cell lymphoma, nasal-type. Copyright © 2005 John Wiley & Sons, Ltd.

To explore the feasibility of construction of the universal nucleic acid vaccine against B-cell lymphoma.RT-PCR was employed to obtain the immuncy losulin heavy chain variable region (IgHV1) gene fragments of the Namalwa cell, normal fetal umbilical cord blood and adult peripheral blood. Then these RT-PCR products were cloned into the eukaryotic expression vector pcDNA3.0 and sequenced. Six plasmids that had high identities with the germ line genes were mixed to serve as vaccines. Eighteen Balb/c mice were divided randomly into three groups and were immunized respectively with the six mixed plasmids, the specific IgHV1 fragment of the Namalwa cell and the blank plasmid pcDNA3.0. 100 microg plasmid and 5 microg hIL-6 per mouse were injected into the muscle, 3 times in 4 weeks. Western blotting and indirect immunofluorescence staining were used to assess the humoral immune responses against the Namalwa cell.The specific humoral immune responses against the Namalwa lymphoma cell could be induced in both the IgHV1-mix group and the Na-IgHV1 group, and the antibodies could recognize the nature antigenic determinants in the surface of the Namalwa cell. The antibodies could be detected since the fourth week after the first immunization, and reached the climax at the sixth week. There was no significant difference of the titers of the antibodies between the two groups. The antibody couldn't be found in the negative control group.The mixed IgHV plasmids can be used as the universal nucleic acid vaccine against the B-cell lymphoma which expresses the same IgHV1 family genes.