Wen Zheng

L-asparaginase in the treatment of refractory and relapsed extranodal NK/T-cell lymphoma, nasal type.

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.

L-Asparaginase—Based Regimen in the Treatment of Refractory Midline Nasal/Nasal-Type T/NK-Cell Lymphoma

Nasal, nasal-type T-cell/natural killer cell (T/NK-cell) lymphoma is a rare disease, and its prognosis is poor. Between March 1992 and March 2002 we investigated a new L-asparaginase-based salvage regimen to treat the disease and improve response to treatment and 5-year overall survival rate. Eighteen patients with refractory midline nasal, nasal-type T/NK-cell lymphoma, who were resistant to a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-like regimen, received an L-asparaginase—based salvage regimen (L-asparaginase, vincristine, and dexamethasone). Primary involved field radiation was given to the patients after chemotherapy.Ten (55.6%) of the patients achieved complete response (CR). Five patients (27.8%) achieved partial response (PR).The overall response rate (CR + PR) was 83.3%.The 5-year overall survival rate was 55.6%. Results of the preliminary clinical study indicated that the L-asparaginase—based salvage regimen significantly improved the response rate and 5-year survival rate.The findings suggested that the therapy is a promising new salvage regimen for treating refractory midline nasal, nasal-type T/NK-cell lymphoma. Int J Hematol. 2003;78:163-167.

Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma.

Abstract The exact incidence and severity of hepatitis B virus (HBV) reactivation after the withdrawal of prophylactic antiviral therapy (delayed HBV reactivation) is unknown. We retrospectively analyzed 107 newly diagnosed diffuse large B cell lymphoma patients with HBV infection who received chemotherapy. The median time from the cessation of antitumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in HBsAg-positive group and 0 in HBsAg-negative/anti-HBc-positive group (P < 0.001). No HBV-related fulminant hepatitis or hepatitis-related death occurred. The multivariate analysis showed that female gender and lengthy cycles of chemotherapy (>8 cycles) were independent risk factors of HBV reactivation in HBsAg-positive patients. In conclusion, prophylactic antiviral therapy could be withdrawn 6 months after the cessation of chemotherapy in HBsAg-negative/anti-HBc-positive patients. However, a longer course of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients.

Hepatitis B surface antigen seroconversion after HBV reactivation in non-Hodgkin's lymphoma.

Reactivation of hepatitis B virus (HBV) can occur in lymphoma patients infected with HBV when they receive chemotherapy or immunotherapy. Prophylactic administration of lamivudine (LAM) reduces the morbidity and mortality associated with HBV reactivation. However, what defines HBV reactivation and the optimal duration of treatment with LAM have not yet been clearly established. HBV reactivation may occur due to the cessation of prophylactic LAM, although re-treatment with nucleoside analogs may sometimes result in hepatitis B surface antigen (HBsAg) seroconversion, which is a satisfactory endpoint for the management of HBV infection. We report a case of HBV reactivation in a 68-year-old HBsAg-positive patient who received rituximab-based immunochemotherapy for follicular lymphoma. HBV reactivation developed following cessation of prophylactic LAM therapy. The patient subsequently received treatment with entecavir (ETV), which led to a rapid and sustained suppression of HBV replication and HBsAg seroconversion. We also appraised the literature concerning HBV reactivation and the role of ETV in the management of HBV reactivation in lymphoma patients. A total of 28 cases of HBV reactivation have been reported as having been treated with ETV during or after immunosuppressive chemotherapy in lymphoma patients. We conclude that ETV is an efficacious and safe treatment for HBV reactivation following LAM cessation in lymphoma patients treated with rituximab-based immunochemotherapy.

Safety and efficacy of bevacizumab combined with R-CHOP regimen in seven Chinese patients with untreated diffuse large B-cell lymphoma.

BackgroundRituximab plus CHOP (R-CHOP) significantly improved the outcome of diffuse large B cell lymphoma (DLBCL), a common sub-type of non-Hodgkin lymphoma. But 40% – 50% of DLBCL patients cannot be cured by this regimen. Some clinical trials showed that bevacizumab might be useful in the treatment of DLBCL. This study evaluated the safety and efficacy of bevacizumab combined with the R-CHOP (A-R-CHOP) regimen in Chinese patients with previously untreated DLBCL.MethodsPatients with previously untreated DLBCL received A-R-CHOP regimen therapy. All patients with complete response (CR)/ unconfirmed complete response(CRu) after 8 cycles of A-R-CHOP received the bevacizumab maintenance therapy once every 3 weeks. The remained bulky disease was treated with radiotherapy.ResultsSeven Chinese patients were treated. All of them had bulky diseases. One patient had progressive disease after 4 cycles of A-R-CHOP therapy. The rest six patients completed 8 cycles of A-R-CHOP treatment. All of these six patients reached CR/CRu (5 CR, 1 CRu). Bevacizumab maintenance therapy was given to 4 CR patients. All 7 patients experienced Grade 3/4 hematologic adverse events; additionally, one had Grade 3 gastrointestinal toxicity and one had Grade 1 epistaxis. During bevacizumab maintenance therapy, one patient had Grade 1 gingival bleeding, another experienced Grade 1 proteinuria and then Grade 3 congestive heart failure 4 months after completion of maintenance therapy. At the end of July 2013, the patient who had progressive disease after 4 cycles of A-R-CHOP died of progressive disease, the other six remained CR response.ConclusionsThe A-R-CHOP regimen is effective for untreated DLBCL, but may cause bevacizumab-specific toxicities, which should be monitored.

Prognostic value of interim (18)F-FDG PET/CT in diffuse large B-cell lymphoma.

OBJECTIVE Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim (18)F-FDG PET/CT after first-line treatment in patients with DLBCL. METHODS Thirty-two patients with DLBCL underwent baseline, interim and post-treatment (18)F-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. RESULTS Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim (18)F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUV(max) cut-off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUV(max) cut-off values were set as 2.0 and 3.0, respectively (P=0.360; P=0.113). CONCLUSIONS Interim PET/CT could predict the prognosis of DLBCL patients with the SUV(max) cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion. KEY WORDS Fludeoxyglucose F18; lymphoma; large cell; diffuse; prognosis; standard utility value.

Aggressive Behavior and Elevated Lactate Dehydrogenase at Baseline Confer Inferior Prognosis in Patients With Primary Cutaneous Lymphoma

BACKGROUND Primary cutaneous lymphoma (PCL) comprises a heterogeneous group of diseases in regard to clinical presentation, histologic appearance, and biological behavior. Its rare occurrence limits analysis of disease features and survival of patients. PATIENTS AND METHODS All patients with PCL treated in our hospital during January 2006 to October 2012 were included in this retrospective study. Their histologic and clinical data were analyzed. The diagnosis of PCL and the evaluation of clinical behavior were based on the 2005 World Health Organization-European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification. RESULTS Fifty-four cases of PCL were included in the study. The median age was 52.5 years. Thirteen (24.1%) patients had B-cell lymphoma and 41 (75.9%) had T-cell lymphoma. Twenty-nine (53.7%) patients exhibited disease having indolent clinical behavior, 14 (25.9%) presented with B symptoms, and 16 (29.6%) had elevated lactate dehydrogenase (LDH) levels at baseline. Within a median follow-up of 47.8 months, the expected 5-year progression-free survival (PFS) rate and overall survival (OS) rate were 6% and 14%, respectively. Using multivariate analysis, aggressive behavior (hazard ratio [HR], 2.92; P = .01] and elevated LDH levels at baseline (HR, 2.88; P = .01) were identified as independent risk factors for PFS. In addition, aggressive behavior (HR, 4.09; P = .01) and elevated LDH levels at baseline (HR, 3.69; P = .01) were also identified as independent risk factors for OS. CONCLUSION The study data suggest that aggressive behavior and elevated LDH levels at baseline were predictive factors for poor PFS and OS, which supports the need for immediate treatment of those patients.

Primary gastrointestinal mantle lymphoma with massive bleeding: a case report and literature review.

The incidence of primary gastrointestinal lymphomas (PGILs) has been increasing. The clinical presentation and treatment of PGIL are distinct from those of nodular lymphomas. Symptoms include abdominal pain, abdominal mass, changes in bowel habits, obstruction, and bleeding. Less life-threatening gastrointestinal bleeding occurs after chemotherapy and few reports have focused on the bleeding of PGILs. We report a case of severe gastrointestinal bleeding caused by low-dose chemotherapy, which was dramatically improved by rituximab monotherapy treatment. The prevention and treatment of gastrointestinal bleeding in PGIL should be given much attention.

A PHASE I STUDY OF CHIMERIC ANTIGEN RECEPTORMODIFIED T CELLS DIRECTED AGAINST CD19 IN PATIENTS WITH RELAPSED OR REFRACTORYCD19(+) B CELL LYMPHOMAS: INTERIM ANALYSIS

271 A PHASE I STUDY OF CHIMERIC ANTIGEN RECEPTORMODIFIED T CELLS DIRECTED AGAINST CD19 IN PATIENTS WITH RELAPSED OR REFRACTORYCD19(+) B CELL LYMPHOMAS: INTERIM ANALYSIS Z. Ying* | X. Xiang | Y. Song | N. Ding | Y. Lin | W. Zheng | X. Wang | N. Lin | M. Tu | Y. Xie | C. Zhang | W. Liu | L. Deng | Y. Liu | Y. Yue | X. Yu | H. Liu | P. Duan | F. Chen | X. Wu | X.F. Huang | L. Jones | X. Kang | S. Chen | J. Zhu Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China; Department of medicine, Marino Biotechnology Co., Ltd., Beijing, China; Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA

PEG-asparaginase in BFM-90 regimen improves outcomes in adults with newly diagnosed lymphoblastic lymphoma

Objective Although L-asparaginase (L-ASP) is a standard treatment for lymphoblastic lymphoma (LBL), hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase (PEG-ASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia (ALL). In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90 regimen (PEG-ASP-BFM-90) for adult LBL. Methods Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEG-ASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China. Results All the 30 patients, including 19 males and 11 females with a median age of 30 (range: 18–62) years, completed 128 times of the PEG-ASP, with the median of 4 (range: 2–6) times. Patients did not receive radiotherapy at this time. The overall response rate was 86.7% (26/30), with 50.0% (15/30) complete response and 36.7% (11/30) partial response. The 3-year overall survival was 46.0% [95% confidence interval (95% CI), 28.2%–64.8%], and the 3-year progression-free survival was 43.0% (95% CI, 25.7%–62.0%). Major adverse events were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded. Conclusions Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapy-related deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and physicians.