Browsing by Author "Li, Ling"

Now showing 1 - 5 of 5
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    ItemOpen Access
    Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma
    (BLOOD, 2016-12-29) Xu-Monette, Zijun Y; Li, Ling; Byrd, John C; Jabbar, Kausar J; Manyam, Ganiraju C; de Winde, Charlotte Maria; van den Brand, Michiel; Tzankov, Alexandar; Visco, Carlo; Wang, Jing; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William WL; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andres JM; Moller, Michael B; Parsons, Ben M; Winter, Jane N; Wang, Michael; Hagemeister, Frederick B; Piris, Miguel A; van Krieken, J Han; Medeiros, L Jeffrey; Li, Yong; van Spriel, Annemiek B; Young, Ken H
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    ItemOpen Access
    CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study.
    (Blood, 2013-04) Hu, Shimin; Xu-Monette, Zijun Y; Balasubramanyam, Aarthi; Manyam, Ganiraju C; Visco, Carlo; Tzankov, Alexander; Liu, Wei-min; Miranda, Roberto N; Zhang, Li; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William WL; Han van Krieken, J; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés JM; Zhao, Xiaoying; Winter, Jane N; Zhang, Mingzhi; Li, Ling; Møller, Michael B; Piris, Miguel A; Li, Yong; Go, Ronald S; Wu, Lin; Medeiros, L Jeffrey; Young, Ken H
    CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30(+) DLBCL had superior 5-year overall survival (CD30(+), 79% vs CD30(-), 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30(+) DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL.
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    Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial.
    (JAMA oncology, 2022-06-16) Wang, Xinhua; Zhang, Lei; Liu, Xiangli; Li, Xin; Li, Ling; Fu, Xiaorui; Sun, Zhenchang; Wu, Jingjing; Zhang, Xudong; Yan, Jiaqin; Chang, Yu; Nan, Feifei; Zhou, Zhiyuan; Wu, Xiaolong; Tian, Li; Ma, Minrui; Li, Zhaoming; Yu, Hui; Zhu, Linan; Wang, Yingjun; Shi, Cunzhen; Feng, Xiaoyan; Li, Jiwei; Ding, Mengjie; Zhang, Jieming; Dong, Meng; Xue, Hongwei; Wang, Jinghua; Zou, Liqun; Su, Liping; Wu, Jianqiu; Liu, Lihong; Bao, Huizheng; Zhang, Liling; Guo, Yanzhen; Guo, Shuxia; Lu, Yi; Young, Ken H; Li, Wencai; Zhang, Mingzhi

    Importance

    The L-asparaginase-based SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen has shown higher response rates and survival benefit over an anthracycline-containing regimen. However, the safety profile was not satisfied. A well-tolerated regimen with promising efficacy is lacking.

    Objective

    To compare the efficacy and safety of the DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) regimen with the SMILE regimen in newly diagnosed advanced-stage (III/IV) extranodal natural killer/T-cell lymphoma (ENKL).

    Design, setting, and participants

    This was an open-label, multicenter, randomized clinical trial that took place across 12 participating hospitals in China from January 2011 to February 2019. Patients were eligible if they were 14 to 70 years old with newly diagnosed ENKL in stages III/IV and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Eligible patients were evenly randomized to either the DDGP or SMILE group.

    Interventions

    Patients in each group were treated with the assigned regimen every 21 days for 6 cycles.

    Main outcomes and measures

    The primary end point was progression-free survival (PFS), and secondary end points included overall response rate and overall survival (OS). The adverse events between the DDGP and SMILE groups were compared.

    Results

    Among the 87 randomized patients, 80 received treatment (40 in the DDGP group and 40 in the SMILE group); the median (IQR) age was 43 (12) years, and 51 (64%) were male. The baseline characteristics were similar between the groups. At a median follow-up of 41.5 months, the median PFS was not reached in the DDGP group vs 6.8 months in the SMILE group (HR, 0.42; 95% CI, 0.23-0.77; P = .004), and the median OS was not reached in the DDGP group vs 75.2 months in the SMILE group (HR, 0.41; 95% CI, 0.19-0.89, P = .02). The PFS rate at 3 years and OS rate at 5 years were higher in the DDGP group vs the SMILE group (3-year PFS, 56.6% vs 41.8%; 5-year OS, 74.3% vs 51.7%). The overall response rate was higher in the DDGP group than in the SMILE group (90.0% vs 60.0%; P = .002). Grade 3 and 4 hematologic toxic effects were more frequently reported in the SMILE group vs the DDGP group (leukopenia, 85.0% vs 62.5%; neutropenia, 85.0% vs 65.0%).

    Conclusions and relevance

    In this randomized clinical trial, the DDGP regimen showed promising preliminary results for patients with newly diagnosed local advanced ENKL. A confirmation trial based on larger population is warranted.

    Trial registration

    ClinicalTrials.gov Identifier: NCT01501149.
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    Expanding anti-CD38 immunotherapy for lymphoid malignancies.
    (Journal of experimental & clinical cancer research : CR, 2022-06-28) Wang, Xu; Yu, Xinfang; Li, Wei; Neeli, Praveen; Liu, Ming; Li, Ling; Zhang, Mingzhi; Fang, Xiaosheng; Young, Ken H; Li, Yong

    Background

    Lymphoid neoplasms, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and NK/T cell neoplasms, are a major cause of blood cancer morbidity and mortality. CD38 (cyclic ADP ribose hydrolase) is a transmembrane glycoprotein expressed on the surface of plasma cells and MM cells. The high expression of CD38 across MM and other lymphoid malignancies and its restricted expression in normal tissues make CD38 an attractive target for immunotherapy. CD38-targeting antibodies, like daratumumab, have been approved for the treatment of MM and tested against lymphoma and leukemia in multiple clinical trials.

    Methods

    We generated chimeric antigen receptor (CAR) T cells targeting CD38 and tested its cytotoxicity against multiple CD38high and CD38low lymphoid cancer cells. We evaluated the synergistic effects of all-trans retinoic acid (ATRA) and CAR T cells or daratumumab against cancer cells and xenograft tumors.

    Results

    CD38-CAR T cells dramatically inhibited the growth of CD38high MM, mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), T-cell acute lymphoblastic leukemia (T-ALL), and NK/T-cell lymphoma (NKTCL) in vitro and in mouse xenografts. ATRA elevated CD38 expression in multiple CD38low cancer cells and enhanced the anti-tumor activity of daratumumab and CD38-CAR T cells in xenograft tumors.

    Conclusions

    These findings may expand anti-CD38 immunotherapy to a broad spectrum of lymphoid malignancies and call for the incorporation of ATRA into daratumumab or other anti-CD38 immunological agents for cancer therapy.
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    PD-1/PD-L1 expression and interaction by automated quantitative immunofluorescent analysis show adverse prognostic impact in patients with diffuse large B-cell lymphoma having T-cell infiltration: a study from the International DLBCL Consortium Program.
    (Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019-06) Li, Ling; Sun, Ruifang; Miao, Yi; Tran, Thai; Adams, Lisa; Roscoe, Nathan; Xu, Bing; Manyam, Ganiraju C; Tan, Xiaohong; Zhang, Hongwei; Xiao, Min; Tzankov, Alexandar; Visco, Carlo; Dybkaer, Karen; Bhagat, Govind; Tam, Wayne; Hsi, Eric D; van Krieken, J Han; You, Hua; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés JM; Møller, Michael B; Piris, Miguel A; Zhang, Mingzhi; Winter, Jane N; Medeiros, L Jeffrey; Rassidakis, George Z; Vaupel, Christine A; Li, Yong; Dakappagari, Naveen; Xu-Monette, Zijun Y; Young, Ken H
    Programmed cell death protein 1/programmed cell death protein ligand1 (PD-1/PD-L1) interaction is an important immune checkpoint targeted by anti-PD-1/PD-L1 immunotherapies. However, the observed prognostic significance of PD-1/PD-L1 expression in diffuse large B-cell lymphoma treated with the standard of care has been inconsistent and even contradictory. To clarify the prognostic role of PD-1/PD-L1 expression and interaction in diffuse large B-cell lymphoma, in this study we used 3-marker fluorescent multiplex immunohistochemistry and Automated Quantitative Analysis Technology to assess the CD3+, PD-L1+, and PD-1+CD3+ expression in diagnostic samples and PD-1/PD-L1 interaction as indicated by presence of PD-1+CD3+ cells in the vicinity of PD-L1+ cells, analyzed their prognostic effects in 414 patients with de novo diffuse large B-cell lymphoma, and examined whether PD-1/PD-L1 interaction is required for the prognostic role of PD-1+/PD-L1+ expression. We found that low T-cell tissue cellularity, tissue PD-L1+ expression (irrespective of cell types), PD-1+CD3+ expression, and PD-1/PD-L1 interaction showed hierarchical adverse prognostic effects in the study cohort. PD-1/PD-L1 interaction showed higher sensitivity and specificity than PD-1+ and PD-L1+ expression in predicting inferior prognosis in patients with high CD3+ tissue cellularity ("hot"/inflammatory tumors). However, both PD-1+ and PD-L1+ expression showed adverse prognostic effects independent of PD-1/PD-L1 interaction, and PD-1/PD-L1 interaction showed favorable prognostic effect in PD-L1+ patients without high CD3+ tissue cellularity. Macrophage function and tumor-cell MYC expression may contribute to the PD-1-independent adverse prognostic effect of PD-L1+ expression. In summary, low T-cell tissue cellularity has unfavorable prognostic impact in diffuse large B-cell lymphoma, and tissue PD-L1+ expression and T-cell-derived PD-1+ expression have significant adverse impact only in patients with high T-cell infiltration. PD-1/PD-L1 interaction in tissue is essential but not always responsible for the inhibitory effect of PD-L1+/PD-1+ expression. These results suggest the benefit of PD-1/PD-L1 blockade therapies only in patients with sufficient T-cell infiltration, and the potential of immunofluorescent assays and Automated Quantitative Analysis in the clinical assessment of PD-1/PD-L1 expression and interaction.