|
|
Presence of multiple abnormal immunologic markers is an independent prognostic factor of diffuse large B-cell lymphoma |
Yiwen Cao1, Zhenhua Liu2, Wen Wu1, Ying Qian1, Qin Shi1, Rong Shen1, Binshen Ouyang3, Pengpeng Xu1, Shu Cheng1, Jin Ye4, Yiming Lu4, Chaofu Wang3, Chengde Yang5, Li Wang1,4(), Weili Zhao1,4() |
1. State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 2. Department of Ultrasonography, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 3. Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 4. Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 5. Department of Rheumatology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China |
|
|
Abstract Autoimmune diseases (ADs) increase the risk of non-Hodgkin’s lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan–Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple (≥3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P<0.001) and OS (68.5% vs. 85.8%, P=0.001) than those without multiple abnormal immunologic markers. Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P=0.008, P<0.001) and OS (P=0.003, P<0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P=0.001) and age>60 years for OS (P=0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.
|
Keywords
immunologic marker
diffuse large B-cell lymphoma
prognosis
|
Corresponding Author(s):
Li Wang,Weili Zhao
|
Just Accepted Date: 10 January 2019
Online First Date: 31 January 2019
Issue Date: 12 March 2019
|
|
1 |
K Ekström Smedby, CM Vajdic, M Falster, EA Engels, O Martínez-Maza, J Turner, H Hjalgrim, P Vineis, A Seniori Costantini, PM Bracci, EA Holly, E Willett, JJ Spinelli, C La Vecchia, T Zheng, N Becker, S De Sanjosé, BC Chiu, L Dal Maso, P Cocco, M Maynadié, L Foretova, A Staines, P Brennan, S Davis, R Severson, JR Cerhan, EC Breen, B Birmann, AE Grulich, W Cozen. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood 2008; 111(8): 4029–4038
https://doi.org/10.1182/blood-2007-10-119974
pmid: 18263783
|
2 |
E Baecklund, A Iliadou, J Askling, A Ekbom, C Backlin, F Granath, AI Catrina, R Rosenquist, N Feltelius, C Sundström, L Klareskog. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006; 54(3): 692–701
https://doi.org/10.1002/art.21675
pmid: 16508929
|
3 |
A Bilici, HS Yapici, S Ercan, M Seker, BB Ustaalioglu, T Salman, A Orcun, M Gumus. The prevalence and significance of autoantibodies in patients with non-Hodgkin’s lymphoma: are they correlated with clinicopathological features? Journal of B.U.ON. 17: 502-507, 2012
pmid: 23033289
|
4 |
R Solans-Laqué A López-Hernandez, JA Bosch-Gil, A Palacios, M Campillo, M Vilardell-Tarres. Risk, predictors, and clinical characteristics of lymphoma development in primary Sjögren’s syndrome. Semin Arthritis Rheum 2011; 41(3): 415–423
https://doi.org/10.1016/j.semarthrit.2011.04.006
pmid: 21665245
|
5 |
E Sabattini, F Bacci, C Sagramoso, SA Pileri. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Pathologica 2010;102(3):83–87.
https://doi.org/10.1590/S0080-623420140000400008
pmid: 21171509
|
6 |
S Ramiro, C Gaujoux-Viala, JL Nam, JS Smolen, M Buch, L Gossec, D van der Heijde, K Winthrop, R Landewé. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73(3): 529–535
https://doi.org/10.1136/annrheumdis-2013-204575
pmid: 24401994
|
7 |
M Petri, AM Orbai, GS Alarcón, C Gordon, JT Merrill, PR Fortin, IN Bruce, D Isenberg, DJ Wallace, O Nived, G Sturfelt, R Ramsey-Goldman, SC Bae, JG Hanly, J Sánchez-Guerrero, A Clarke, C Aranow, S Manzi, M Urowitz, D Gladman, K, Kalunian M Costner, VP Werth, A Zoma, S Bernatsky, G Ruiz-Irastorza, MA Khamashta, S Jacobsen, JP Buyon, P Maddison, MA Dooley, RF van Vollenhoven, E Ginzler, T Stoll, C Peschken, JL Jorizzo, JP Callen, SS Lim, BJ Fessler, M Inanc, DL Kamen, A Rahman, K Steinsson, AG Jr Franks, L Sigler, S Hameed, H Fang, N Pham, R Brey, MH Weisman, G Jr McGwin, LS Magder. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64(8): 2677–2686
https://doi.org/10.1002/art.34473
pmid: 22553077
|
8 |
CH Shiboski, SC Shiboski, R Seror, LA Criswell, M Labetoulle, TM Lietman, A Rasmussen, H Scofield, C Vitali, SJ Bowman, X Mariette; International Sjögren’s Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol 2017; 69(1):35–45
https://doi.org/10.1002/art.39859
pmid: 27785888
|
9 |
IF Horvath, P Szodoray, M Zeher. Primary Sjögren’s syndrome in men: clinical and immunological characteristic based on a large cohort of Hungarian patients. Clin Rheumatol 2008; 27(12): 1479–1483
https://doi.org/10.1007/s10067-008-0944-7
pmid: 18553114
|
10 |
N Watanabe, A Arimura, M Kobayashi, M Oshima. ASO, ASK and ADNase-B values rheumatic fever, rheumatic heart disease and other infections by hemolytic streptococcus: Proceedings of the IV Conference on Prevention for Rheumatic Fever and Rheumatic Heart Disease, January 1979, Kyoto. Jpn Circ J 1980; 44(10): 808–809
https://doi.org/10.1253/jcj.44.808
pmid: 7431636
|
11 |
K Ohyama, M Baba, M Tamai, N Aibara, K Ichinose, N Kishikawa, A Kawakami, N Kuroda. Proteomic profiling of antigens in circulating immune complexes associated with each of seven autoimmune diseases. Clin Biochem 2015; 48(3): 181–185
https://doi.org/10.1016/j.clinbiochem.2014.11.008
pmid: 25438073
|
12 |
H Tsukamoto, A Ueda, K Nagasawa, Y Tada, Y Niho. Increased production of the third component of complement (C3) by monocytes from patients with systemic lupus erythematosus. Clin Exp Immunol 1990; 82(2): 257–261
https://doi.org/10.1111/j.1365-2249.1990.tb05436.x
pmid: 2242606
|
13 |
BD Cheson, B Pfistner, ME Juweid, RD Gascoyne, L Specht, SJ Horning, B Coiffier, RI Fisher, A Hagenbeek, E Zucca, ST Rosen, S Stroobants, TA Lister, RT Hoppe, M Dreyling, K Tobinai, JM Vose, JM Connors, M Federico, V; International Harmonization Project on Lymphoma. DiehlRevised response criteria for malignant lymphoma. J Clin Oncol 2007; 25(5): 579–586
https://doi.org/10.1200/JCO.2006.09.2403
pmid: 17242396
|
14 |
J Candido, T Hagemann. Cancer-related inflammation. J Clin Immunol 2013; 33( Suppl 1): S79–S84
https://doi.org/10.1007/s10875-012-9847-0
pmid: 23225204
|
15 |
U Vitolo, A Chiappella, E Angelucci, G Rossi, AM Liberati, MG Cabras, B Botto, G Ciccone, G Gaidano, L Falchi, R Freilone, D Novero, L Orsucci, V Pavone, E Pogliani, D Rota-Scalabrini, F Salvi, A Tonso, A Tucci, A; Gruppo Italiano Multiregionale Linfomi e Leucemie (GIMURELL). LevisDose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study. Haematologica 2009; 94(9): 1250–1258
https://doi.org/10.3324/haematol.2009.007005
pmid: 19586937
|
16 |
ET Sayegh, O Bloch, AT Parsa. Complement anaphylatoxins as immune regulators in cancer. Cancer Med 2014; 3(4): 747–758
https://doi.org/10.1002/cam4.241
pmid: 24711204
|
17 |
M Fallah, X Liu, J Ji, A Försti, K Sundquist, K Hemminki. Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study. Ann Oncol 2014; 25(10): 2025–2030
https://doi.org/10.1093/annonc/mdu365
pmid: 25081899
|
18 |
O Ngalamika, Y Zhang, H Yin, M Zhao, ME Gershwin, Q Lu. Epigenetics, autoimmunity and hematologic malignancies: a comprehensive review. J Autoimmun 2012; 39(4): 451–465
https://doi.org/10.1016/j.jaut.2012.09.002
pmid: 23084980
|
19 |
SM Hayter, MC Cook. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev 2012; 11(10): 754–765
https://doi.org/10.1016/j.autrev.2012.02.001
pmid: 22387972
|
20 |
GS Firestein. Evolving concepts of rheumatoid arthritis. Nature 2003; 423(6937): 356–361
https://doi.org/10.1038/nature01661
pmid: 12748655
|
21 |
S Bernatsky, A Clarke, R Ramsey-Goldman. Malignancy and systemic lupus erythematosus. Curr Rheumatol Rep 2002; 4(4): 351–358
https://doi.org/10.1007/s11926-002-0045-6
pmid: 12126588
|
22 |
RI Fox, HI Kang. Pathogenesis of Sjogren’s syndrome. Rheum Dis Clin North Am 1992; 18(3):517–538 PMID: 1323135
https://doi.org/10.1097/BOR.0b013e32832eba21
|
23 |
H Nogai, B Dörken, G Lenz. Pathogenesis of non-Hodgkin’s lymphoma. J Clin Oncol 2011; 29(14): 1803–1811
https://doi.org/10.1200/JCO.2010.33.3252
pmid: 21483013
|
24 |
SA Riemersma, ES Jordanova, RF Schop, K Philippo, LH Looijenga, E Schuuring, PM Kluin. Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites. Blood 2000; 96(10): 3569–3577
https://doi.org/10.2307/3343410
pmid: 11071656
|
25 |
E Lech-Maranda, J Bienvenu, AS Michallet, R Houot, T Robak, B Coiffier, G Salles. Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B-cell lymphoma. Eur Cytokine Netw 2006; 17(1): 60–66
https://doi.org/10.1097/01.COH.0000209585.67081.22
pmid: 16613764
|
26 |
LM Rimsza, RA Roberts, TP Miller, JM Unger, M LeBlanc, RM Braziel, DD Weisenberger, WC Chan, HK Muller-Hermelink, ES Jaffe, RD Gascoyne, E Campo, DA Fuchs, CM Spier, RI Fisher, J Delabie, A Rosenwald, LM Staudt, TM Grogan. Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood 2004; 103(11): 4251–4258
https://doi.org/10.1182/blood-2003-07-2365
pmid: 14976040
|
27 |
KY Urayama, RF Jarrett, H Hjalgrim, A Diepstra, Y Kamatani, A Chabrier, V Gaborieau, A Boland, A Nieters, N Becker, L Foretova, Y Benavente, M Maynadié, A Staines, L Shield, A Lake, D Montgomery, M Taylor, KE Smedby, RM Amini, HO Adami, B Glimelius, B Feenstra, IM Nolte, L Visser, GW van Imhoff, T Lightfoot, P Cocco, L Kiemeney, SH Vermeulen, I Holcatova, L Vatten, GJ Macfarlane, P Thomson, DI Conway, S Benhamou, A Agudo, CM Healy, K Overvad, A Tjønneland, B Melin, F Canzian, KT Khaw, RC Travis, PH Peeters, CA González, JR Quirós, MJ Sánchez, JM Huerta, E Ardanaz, M Dorronsoro, F Clavel-Chapelon, HB Bueno-de-Mesquita, E Riboli, E Roman, P Boffetta, S de Sanjosé, D Zelenika, M Melbye, A van den Berg, M Lathrop, P Brennan, JD McKay. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. J Natl Cancer Inst 2012; 104(3): 240–253
https://doi.org/10.1093/jnci/djr516
pmid: 22286212
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|