ALBERT

Description: Epstein-Barr virus (EBV) infection can modify the cytokine expression profiles of host cells and determine the fate of those cells. Of note, expression of interleukin-13 (IL-13) may be detected in EBV-associated Hodgkin lymphoma and the natural killer (NK) cells of chronic active EBV-infected patients, but its biologic role and regulatory mechanisms are not understood. Using cytokine antibody arrays, we found that IL-13 production is induced in B cells early during EBV infection. Furthermore, the EBV lytic protein, Zta (also known as the BZLF-1 product), which is a transcriptional activator, was found to induce IL-13 expression following transfection. Mechanistically, induction of IL-13 expression by Zta is mediated directly through its binding to the IL-13 promoter, via a consensus AP-1 binding site. Blockade of IL-13 by antibody neutralization showed that IL-13 is required at an early stage of EBV-induced proliferation and for long-term maintenance of the growth of EBV immortalized lymphoblastoid cell lines (LCLs). Thus, Zta-induced IL-13 production facilitates B-cell proliferation and may contribute to the pathogenesis of EBV-associated lymphoproliferative disorders, such as posttransplantation lymphoproliferative disease (PTLD) and Hodgkin lymphoma.

Description: Introduction: Rituximab is a chimeric monoclonal antibody against the protein CD20 and has been wildly used in the treatment of CD20-positive, B-cell Non-Hodgkin's Lymphoma (NHL). Many studies have demonstrated the effect and safety of Rituximab both in China and international. However, the pattern of real-world Rituximab use in China still remains unclear, although the country is trying very hard to lower the barrier of anti-cancer drug access. In this study, we reported the pattern of Rituximab use during initial treatment and factors associated with Rituximab use among B-cell NHL patients in China Lymphoma Patient Registry (CLAP) study (NCT03313271). Method: CLAP is a multi-center observational bi-directional cohort study based on medical records of hospitalized lymphoma patients and was launched in early 2017 in five hospitals. Medical records of the eligible patients in participating hospitals were systematically reviewed and study data were manually entered or directly transferred into a predesigned electronic database with the support of Medbanks Network Technology Co., Ltd. Its inclusion criteria include: 1) newly diagnosed as lymphoma in participating hospitals; 2) age 〉=18 yrs old at time of disease diagnosed; 3) given informed consent if prospective follow-up is needed. In order to be eligible for this particular report, three additional criteria were applied: 1) diagnosis was made after July 2015; 2) with clear diagnosis of one of B-cell NHL subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL); 3) with recorded initial treatment. Frequency analysis was used to describe the distribution of patient demographics and disease characteristics, stratified by if Rituximab was used. Rituximab use was defined as YES if at least one prescription was made regardless of number of cycles and duration of treatment. Percentage of Rituximab use was also reported by histology subtypes and first prescription time (every 6 months). Multiple logistic regression was used to explore factors associated with Rituximab use during initial treatment. Result: A total of 1634 study subjects were included in this analysis and 1258 of them were treated with Rituximab contained regimen. Among all study subjects, male was slightly more than female (52.4% vs 47.6%) and 85.7% of them were older than 40 yrs. Majority of study subjects (84.9)% had a ECOG score between 0-1 at time of disease diagnosis. The distribution of demographic and disease characteristics was similar between the two groups (Table1). Among the five subtypes, patients with FL had the highest rate of Rituximab use (80.8%), followed by DLBCL (77.2%), MZL (74.3%), MCL (73.3%) and CLL/SLL (57.1%) (Figure1). Using every 6 months as a time period, Rituximab use rate between July 2015 and March 2018 was 71.8%, 77.9%, 70.6%, 78.8%, 87.9% and 93.8% , p-value for trend test was 0.0002(figure2). In multiple logistic regression, CLL/SLL was associated with less Rituximab use comparing with DLBCL (OR=0.439; 95% CI=0.228-0.846) and later time of first prescription was associated with more Rituximab use (OR=1.192; 95% CI=1.088-1.305). Conclusion Closed to 77% B-cell NHL patients received Rituximab contained regimen as their initial treatment, demonstrating the well recognition of the efficacy and safety of Rituximab among doctors in CLAP hospitals. Compared with other subtypes, patients with CLL/SLL had lower Rituximab use rate, which might be contributed to its lower CD20 express (Beum et.al, J Immunol 2006) and suboptimal clinical effect (Robak et.al, J Clin Oncol 2010). In September 2017, Rituximab was covered by the National Basic Medical Insurance and the price was also dropped. Therefore, as a proxy of payment policy improvement and lower access barrier, later time of diagnosis was associated with higher Rituximab use rate. Although not statistical significant, patients with poorer health status (ECOG〉=2) was more likely to be prescribed with Rituximab. In conclusion, NHL subtypes and economic reason are two main driven factors that influence the use of Rituximab as initial treatment in real world practice in China. Disclosures Song: Peking University Cancer Hospital (Beijing Cancer Hospital): Employment. Zhu:Beijing Cancer Hospital: Employment.

Description: Background: Cysteine and glycine-rich protein 2 (CSRP2), a member of the CSRP family, is reported to be upregulated in highly invasive breast cancer cells and promote breast cancer cell invasiveness. The expression and clinical implications of CSRP2 have not been explored in B-cell acute lymphoblastic leukemia (ALL). Aims: To investigate the expression of human CSRP2 messenger RNA and explore its clinical implications in adult B-cell ALL. Methods: TaqMan fluorescent real-time quantitative polymerase chain reaction (qPCR) was used to quantify CSRP2 mRNA copy number in bone marrow samples from patients with B-cell ALL and control normal bone marrow samples from healthy allogeneic stem cell transplantation donors (HD). Results: CSRP2 was expressed at significantly higher levels in 232 newly-diagnosed B-cell ALL marrow samples (ND; median 63.8%; range 0-1368.1%) than 43 HD samples (median 0.4%; range 0-1.8%; P

Description: Abstract Background: Chemokine (C-C Motif) Ligand 17 is a protein coding gene. This chemokine plays important roles in T cell development in thymus as well as in trafficking and activation of mature T cells. Diseases associated with CCL17 include mycosis fungoides, paragonimiasis and some hematologic malignancies such as Hodgkin¡¯s lymphoma, B cell lymphoma, and Nasal natural killer/T cell lymphoma (NNKTL). However, our knowledge of the expression levels of CCL17 in B-cell acute lymphoblastic leukemia (ALL) remains limited. Aims: The purpose of this study was to investigate the expression levels of human CCL17 messenger RNA in adult B-cell ALL. Methods: A real-time quantitative reverse transcription-polymerase chain reaction assay based on TaqMan fluorescence methodology was used to quantify the CCL17 mRNA copy number in the bone marrow cells from patients with adult leukemia and in 16 human hematologic malignant cell lines. Normal marrow samples from the allogeneic stem cell transplantation donors were served as control. Informed consent was obtained for every marrow sample. Results: Expression levels of the CCL17 gene in leukemic cell lines, leukemia patients and normal donor marrow are shown in Figure 1. These results showed that the relative levels of CCL17 gene expression in marrow from 189 newly diagnosed B-cell ALL(median 0.23%; range 0%¡«69000%) was significantly higher than those of bone marrow from the 43 healthy donors (median 0.05%; range 0%¡«6.87%;P =0.0007). Significant CCL17 mRNA overexpression was found in the de novo B-cell ALL patients compared with 102 treated B-cell ALL patients(median 0.02%; range 0%¡«3339%) who achieved complete remission or 70 de novo AML (median 0.02%; range 0%¡«9.132%;P¡¯s 0.05), but it was higher in SupB15 and Nalm-6 cells from B-cell ALL cell lines than in other cells from AML or T-cell ALL cell lines. Conclusion: These results suggest that abnormal expression of CCL17 in leukemia may be involved in the pathomechanism of B-cell ALL. Figure 1 A: CCL17 expression levels in B-cell ALL and healthy donors( ** represent P〈 0.01). B: CCL17 expression levels in human hematologic malignant cell lines. Figure 1. A: CCL17 expression levels in B-cell ALL and healthy donors( ** represent P〈 0.01). / B: CCL17 expression levels in human hematologic malignant cell lines. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Lymphoma is the most common hematologic tumor. In 2015 about 88000 new cases was estimated diagnosed in China (Chen et.al, CA Cancer J Clin 2016). China Lymphoma Patient Registry (CLAP) (NCT03313271) is an observational bi-directional cohort study launched in five hospitals in early 2017, aiming to better understand the epidemiology, treatment and prognosis of lymphoma in the country. By the end of March 2018, a total of 3458 lymphoma patients, including 412 Hodgkin's Lymphoma (HL) cases and 3046 Non-Hodgkin's Lymphoma (NHL) cases, had been prospectively and retrospectively recruited. Here we report the demographic and disease baseline characteristics of 3046 NHL patients diagnosed between July 2015 and March 2018. Method This is an observational bi-directional cohort study based on medical records of hospitalized lymphoma patients in five CLAP hospitals. In order to be eligible for this particular analysis, patients need to be 1) newly diagnosed as NHL between July 2015 and March 2018 in five participating hospitals; 2) age 〉=18 yrs old at time of disease diagnosis; 3) given informed consent if prospective follow-up is needed. This study has been approved by Institutional Review Board (IRB) from all study sites. Medical records of newly diagnosed NHL patients were systematically reviewed and study data were manually entered or directly transferred into a predesigned electronic database with the support of Medbanks Network Technology Co., Ltd. Descriptive analysis was used to understand the distribution of patient demographic information (age, gender, medical history, etc.), disease baseline characteristics (symptoms, score, stage, etc.) and initial treatment options (if Rituximab) for NHL population as a whole as well as by subtype stratification. Result A total of 3046 newly diagnosed NHL patients were identified between July 2015 and March 2018, and diffuse large B cell lymphoma (DLBCL) was the most common subtype (48.2%)(Figure1). Males accounted for 55.4% of the total study population and were very dominant in mantle cell lymphoma (MCL) (79.8%), but females were more common in Follicular lymphoma (FL) (53.7%) and Marginal zone lymphoma (MZL) (52.8%). The median age of all study subjects was 58yrs old (range 18-95) and patients with FL (51yrs) and T-cell lymphoma (TCL) (52yrs) was relative younger compared with other subtypes. The general health status of most NHL patients was relative good at first diagnosis, the percentage (excluding missing) of patient with recorded B symptoms, ECOG-PS score 〉=2 and IPI score3-5 were 39.0%, 4.8% and 26.8%, respectively. Among B-cell lymphoma (BCL), Rituximab was most frequently used in patients with FL (63.4%) followed by DLBCL (61.1%), and MCL (58.5%) (table1). Hypertension was the most common comorbidity and over 16% NHL patients had reported concomitant hypertension followed by diabetes (7.9%), hepatitis B (4.4%), coronary heart disease (3.3%) and tuberculosis (1.4%) (Figure2). Previous personal history of cancer and family history of cancer were reported by 2.8% and 12.5% of study subjects, respectively (Figure3). Conclusion Among all CLAP participants, NHL accounts for nearly 90% of all lymphoma patients, which is consistent with the report from national cancer registry (He, Chen, Chinese Cancer Registry Annual Report 2016) and demonstrates a well representativeness of NHL patients in China. NHL is a composite of many types of lymphoma and each subtype had unique histological, clinical and prognostic characteristics. Although previous studies had reported the pathology distribution of NHL in China (Sun et.al, Am J Clin Pathol 2012; Cao et.al, Ann Diagn Pathol. 2018), very few have more detailed information on disease characteristics and treatment. As a big observational study focus on lymphoma, this registry provides a unique opportunity and platform to understand the whole picture of NHL diagnosis, treatment and prognosis in real world. Disclosures Song: Peking University Cancer Hospital (Beijing Cancer Hospital): Employment. Zhu:Beijing Cancer Hospital: Employment.

Description: Introduction Lymphoma is the most common hematologic tumor with about 88000 newly diagnosed cases in China in 2015 (Chen et.al, CA Cancer J Clin 2016). To better understand the epidemiology, treatment and prognosis of lymphoma in China, Beijing Cancer Hospital and other four hospitals jointly launched China Lymphoma Patient Registry (CLAP) study (NCT03313271) in early 2017. By the end of March 2018, a total of 3458 lymphoma patients, including 412 Hodgkin's Lymphoma (HL) cases and 3046 Non-Hodgkin's Lymphoma (NHL) cases, had been prospectively and retrospectively recruited. Here we report the baseline characteristics and initial treatment of HL patients diagnosed between July 2015 and March 2018. Method This is an observational bi-directional cohort study based on medical records of hospitalized lymphoma patients. Inclusion criteria of this study include: 1) newly diagnosed as HL after July 2015 in five participating hospitals; 2) age 〉=18 yrs old at time of disease diagnosed; 3) given informed consent if prospective follow-up is needed. This study has been approved by Institutional Review Board (IRB) of all study sites. Medical records of newly diagnosed adult HL patients in five participating hospitals were systematically reviewed. Study data, including patient demographic information, disease baseline characteristics, treatment options and prognosis were manually entered or directly transferred into a predesigned electronic database with the support of Medbanks Network Technology Co., Ltd. In this study, descriptive analysis was used to understand the distribution of patient demographic information (age, gender, medical history, etc.), disease baseline characteristics (symptom, score, stage, etc.) and initial treatment option (if ABVD) for HL population as a whole as well as by subtype stratification. Result A total of 412 HL patients were identified between July 2015 and March 2018. Among all HL patients, nodular sclerosis type of classic Hodgkin's lymphoma (NSCHL) was the most common subtype (53.6%) followed by mixed cell type of classic Hodgkin's lymphoma (MCCHL) (23.1%)(Figure1). All classic subtypes accounted for over 93% of all HL patients. Male is more common than female (60.4%vs39.6%), especially for nodular lymphocytes predominant type of HL (NLPHL). However, no statistical significant gender difference was observed across different subtypes. Age of NSCHL patients was relative younger than patients with other subtypes with a median age of 31. The general health status of most HL patients was relative good at first diagnosis, the percentage (excluding missing) of patient with recorded B symptoms and ECOG score 〉=2 were 42.4% and 2%, respectively. The distribution of clinical staging was 4.9%, 46.1%, 18.2% and 26.5% for I-IV respectively. Doxorubicin, Bleomycin, Vincristine, Dacarbazine (ABVD) contained regimen was the most common initial treatment regimen and was received by 72% of HL patients and no statistical significant difference was observed in term of ABVD use across HL subtypes (Table1). Hypertension was the most common comorbidity and 7% HL patients had reported concomitant hypertension followed by diabetes (4.4%), hepatitis B (1.9%) and tuberculosis (1.0%) (Figure2). Previous personal history of cancer and family history of cancer were reported by 1.7% and 9.2% of study subjects, respectively (Figure3). Conclusion Compared with Non-Hodgkin's Lymphoma, HL is less common, less aggressive and attracts less attention from researchers. In 2013, only about 700 HL newly diagnosed cases were reported, accounting for 5.4% of total lymphoma patients in the country (He, Chen, Chinese Cancer Registry Annual Report 2016). Although some multi-center studies had reported the pathology distribution of HL (Sun et.al, Am J Clin Pathol 2012; Cao et.al, Ann Diagn Pathol. 2018), very few of them have more detailed information on disease characteristics and treatment. As one of the biggest observational studies focus on HL in the country as well as in the region, this registry provides a unique opportunity and platform to understand the whole picture of HL diagnosis, treatment and prognosis in real world. Disclosures Song: Peking University Cancer Hospital (Beijing Cancer Hospital): Employment. Zhu:Beijing Cancer Hospital: Employment.

Description: Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV+ patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; Ptrend 〈 .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV+ patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike.