Distinct clinical characteristics draw a new prognostic model for splenic marginal zone lymphoma in HBV high prevalent region

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Abstract

Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell neoplasm with hepatitis virus supposed to involve in the pathogenesis. The characteristics of SMZL derived from Caucasia population and high hepatitis C virus (HCV) infection region have been widely investigated, but few was reported in the Eastern population with HBV prevalent region. We analyzed the clinical characteristics, cytogenetic aberrations and prognostic factors in 160 SMZL patients from China. 25 patients (16%) were HBsAg-positive and 54 (34%) patients with resolved HBV infection. IGH gene usage was analyzed in 39 patients. The preferential usages of IGHV genes were IGHV1-2 (26%), followed by IGHV4-34 (18%) and IGHV2-70 (10%). The patients with HBV infection presented biased IGHV-D-J rearrangements and mutational status. Using three independent factors hemoglobin level, HBsAg positivity and complex karyotype, we developed a new hierarchical prognostic model, which showed a better c-index than the previously reported IIL and HPLL scoring systems in SMZL. In conclusion, SMZL in HBV prevalent region have unique clinical and biological characteristics and new prognostic scoring model should be adopted in this population.

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Most cited references 33

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Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination.

Xiaofeng Liang, Shengli Bi, Weizhong Yang … (2009)

To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants. National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA. The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age <15 years compared to that found in the 1992 national serosurvey, and among children age <5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other). China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16-20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.

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Splenic marginal zone lymphoma: a prognostic model for clinical use.

Emilio Iannitto, Sonia A. Tucci, N. COLOMBO … (2006)

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100,000/microL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient.

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IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas.

M Parrens, D. RIZZO, Frederick A. Schmitt … (2012)

To clarify the relationships between marginal zone lymphomas (MZLs) and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (WM/LPLs), immunoglobulin heavy chain variable gene (IGHV) features were analyzed and the occurrence of MYD88 L265P mutations was identified in a series of 123 patients: 53 MZLs from the spleen (SMZLs), 11 from lymph nodes (NMZLs), 28 mucosa-associated lymphatic tissue (MALT) lymphomas and 31 WM/LPLs. SMZLs were characterized by overrepresentation of IGHV1-2 gene rearrangements with a canonical motif, without selection pressure and with long CDR3 segments. NMZLs had increased frequencies of IGHV3 genes. The IGHV gene was unmutated in most cases, often with long CDR3 segments. MALT lymphomas were usually associated with a mutated IGHV gene, but with the absence of selection pressure. WM/LPLs were associated with an IGHV3-23 overrepresentation and high IGHV mutation rate, with features of selection pressure and short CDR3 segments. MYD88 L265P mutations were almost restricted exclusively to WM/LPL patients. Taken all diagnoses together, all patients with MYD88 L265P mutations had an immunoglobulin M peak and almost all patients except one had bone marrow infiltration. These results demonstrate that the history of antigen exposure of the four entities studied was different and MYD88 L265P was specifically associated with WM/LPLs. WM/LPL may thus be functionally associated with constitutive nuclear factor-κB activation.

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Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 17 November 2017

Publication date (Electronic): 19 October 2017

Volume: 8

Issue: 58

Pages: 98757-98770

Affiliations

¹ State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China

Author notes

Correspondence to: Lugui Qiu, qiulg@ 123456ihcams.ac.cn

Article

Publisher ID: 21931

DOI: 10.18632/oncotarget.21931

PMC ID: 5716765

PubMed ID: 29228725

SO-VID: 9f17c0dc-a960-4650-baf3-c5ac33ab01ea

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This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

Distinct clinical characteristics draw a new prognostic model for splenic marginal zone lymphoma in HBV high prevalent region

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Karger: Oncology

Most cited references 33

Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination.

Splenic marginal zone lymphoma: a prognostic model for clinical use.

IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas.

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