Population based registry study on large B-cell lymphoma mortality and morbidity in Finland

Authors

DOI:

https://doi.org/10.2340/1651-226X.2025.42539

Keywords:

DLBCL, comorbidities, mortality, LBCL, survival

Abstract

Background: Large B-cell lymphomas (LBCLs) form a notable subgroup of lymphomas; however, their associated long-term comorbidities and mortality rates remain under-researched in real-world settings.

Material and methods: This nationwide Finnish population-based matched cohort study included virtually all LBCL patients (N = 7,019) diagnosed from 2008 to 2019, alongside age, sex, and region-matched controls (1:1 ratio) without lymphoma. Diagnoses of LBCLs were obtained from the Finnish Cancer Registry, with data linked to additional nationwide registries. Baseline characteristics were summarised using descriptive statistics. Overall survival (OS) was estimated using the Kaplan-Meier method, while Cox regression was used to analyse factors associated with OS and evaluate the risk and associated factors of comorbidities considering the competing risk of death.

Results: The 5-year survival rate for LBCL patients, median age 70.7 years and 52.7% male, was 50.0% (95% Confidence Interval [CI] 48.7% – 51.3%), compared to 82.6% (95% CI 81.5% – 83.6%) for controls. Among LBCL patients, older age and a higher Charlson comorbidity index were associated with increased mortality. Conversely, female sex, later diagnosis year, and radiation therapy were associated with improved survival. Patients with LBCL exhibited an elevated risk of long-term comorbidities, including solid tumours, hematological and skin cancers, lung and thyroid diseases, mental and behavioral disorders, and cardiovascular diseases. After 12 years of follow-up, lymphoma accounted for the primary cause of death in approximately 43% of LBCL patients.

Interpretation: Large B-cell lymphomas are linked with significant long-term comorbidities and elevated mortality rates.

Downloads

Download data is not yet available.

References

Susanibar‐Adaniya S, Barta SK. 2021 Update on diffuse large B cell lymphoma: a review of current data and potential applications on risk stratification and management. Am J Hematol. 2021;96:617–29.

https://doi.org/10.1002/ajh.26151 DOI: https://doi.org/10.1002/ajh.26151

Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018;50:74–87.

https://doi.org/10.1016/j.pathol.2017.09.006 DOI: https://doi.org/10.1016/j.pathol.2017.09.006

Nastoupil LJ, Bartlett NL. Navigating the evolving treatment landscape of diffuse large B-cell lymphoma. JCO. 2023;41:903–13.

https://doi.org/10.1200/JCO.22.01848 DOI: https://doi.org/10.1200/JCO.22.01848

Ekberg S, Jerkeman M, Andersson P, Enblad G, Wahlin BE, Hasselblom S, et al. Long‐term survival and loss in expectancy of life in a popu-lation‐based cohort of 7114 patients with diffuse large B‐cell lymphoma. Am J Hematol. 2018;93:1020–8.

https://doi.org/10.1002/ajh.25147 DOI: https://doi.org/10.1002/ajh.25147

Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

https://doi.org/10.1056/NEJMoa011795 DOI: https://doi.org/10.1056/NEJMoa011795

Maurer MJ, Ghesquières H, Jais J-P, Witzig TE, Haioun C, Thompson CA, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. JCO. 2014;32:1066–73.

https://doi.org/10.1200/JCO.2013.51.5866 DOI: https://doi.org/10.1200/JCO.2013.51.5866

Abu Sabaa A, Mörth C, Hasselblom S, Hedström G, Flogegård M, Stern M, et al. Age is the most important predictor of survival in diffuse large B‐cell lymphoma patients achieving event‐free survival at 24 months: a Swedish population‐based study. Br J Haematol. 2021;193:906–14.

https://doi.org/10.1111/bjh.17206 DOI: https://doi.org/10.1111/bjh.17206

Howlader N, Mariotto AB, Besson C, Suneja G, Robien K, Younes N, et al. Cancer‐specific mortality, cure fraction, and noncancer causes of death among diffuse large B‐cell lymphoma patients in the immunochemotherapy era. Cancer. 2017;123:3326–34.

https://doi.org/10.1002/cncr.30739 DOI: https://doi.org/10.1002/cncr.30739

Jakobsen LH, Bøgsted M, Brown PDN, Arboe B, Jørgensen J, Larsen TS, et al. Minimal loss of lifetime for patients with diffuse large B-cell lymphoma in remission and event free 24 months after treatment: a Danish population-based study. JCO. 2017;35:778–84.

https://doi.org/10.1200/JCO.2016.70.0765 DOI: https://doi.org/10.1200/JCO.2016.70.0765

Witkowska M, Majchrzak A, Smolewski P. The role of radiotherapy in Hodgkin’s lymphoma: what has been achieved during the last 50 years? BioMed Res Int. 2015;2015:1–8.

https://doi.org/10.1155/2015/485071 DOI: https://doi.org/10.1155/2015/485071

Harkins RA, Patel SP, Flowers CR. Cost burden of diffuse large B-cell lymphoma. Expert Rev Pharmacoecon Outcomes Res. 2019;19:645–61.

https://doi.org/10.1080/14737167.2019.1680288 DOI: https://doi.org/10.1080/14737167.2019.1680288

Wang H-I, Smith A, Aas E, Roman E, Crouch S, Burton C, et al. Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort. Eur J Health Econ. 2017;18:255–67.

https://doi.org/10.1007/s10198-016-0775-4 DOI: https://doi.org/10.1007/s10198-016-0775-4

Sund R. Quality of the Finnish Hospital Discharge Register: a systematic review. Scand J Public Health. 2012;40:505–15.

https://doi.org/10.1177/1403494812456637 DOI: https://doi.org/10.1177/1403494812456637

Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173:676–82.

https://doi.org/10.1093/aje/kwq433 DOI: https://doi.org/10.1093/aje/kwq433

Wang J, Zhou M, Zhou R, Xu J, Chen B. Nomogram for predicting the overall survival of adult patients with primary gastrointestinal diffuse large B cell lymphoma: a SEER- based study. Front Oncol. 2020;10:1093.

https://doi.org/10.3389/fonc.2020.01093 DOI: https://doi.org/10.3389/fonc.2020.01093

Tuominen S, Uusi-Rauva K, Blom T, Jyrkkiö S, Tuppurainen K, Alanne E. Real-world data on diffuse large B-cell lymphoma in 2010–2019: usability of large data sets of Finnish hospital data lakes. Future Oncol. 2022;18:1103–14.

https://doi.org/10.2217/fon-2021-0806 DOI: https://doi.org/10.2217/fon-2021-0806

Puhakka I, Kuitunen H, Jäkälä P, Sonkajärvi E, Turpeenniemi-Hujanen T, Rönkä A, et al. Primary central nervous system lymphoma high incidence and poor survival in Finnish population-based analysis. BMC Cancer. 2022;22:236.

https://doi.org/10.1186/s12885-022-09315-8 DOI: https://doi.org/10.1186/s12885-022-09315-8

Vaughn JL, Epperla N. Survival of patients with transformed follicular lymphoma in the United States: a multiple cohort study. Biomark Res. 2023;11:84.

https://doi.org/10.1186/s40364-023-00525-1 DOI: https://doi.org/10.1186/s40364-023-00525-1

Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBDO, Berti E, et al. The 5th edition of the World Health Organization classifi-cation of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022;36:1720–48.

https://doi.org/10.1038/s41375-022-01620-2 DOI: https://doi.org/10.1038/s41375-022-01620-2

Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. The World Health Organization classification of hemato-logical malignancies report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Mod Pathol. 2000;13:193–207.

https://doi.org/10.1038/modpathol.3880035 DOI: https://doi.org/10.1038/modpathol.3880035

Ermann DA, Vardell VA, Shah H, Fitzgerald L, Tao R, Gaffney DK, et al. Survival outcomes of limited-stage diffuse large B-cell lymphoma treated with radiation therapy. Clin Lymphoma Myeloma and Leuk. 2024;24:94–104.e6.

https://doi.org/10.1016/j.clml.2023.09.006 DOI: https://doi.org/10.1016/j.clml.2023.09.006

Glimelius I, Ekberg S, Ekström Smedby K, Wästerlid T. Stable use of radiotherapy in lymphoma patients over time – a comprehensive national overview of radiotherapy use in Sweden with focus on older patients. Clin Transl Radiat Oncol. 2024;46:100785.

https://doi.org/10.1016/j.ctro.2024.100785 DOI: https://doi.org/10.1016/j.ctro.2024.100785

Tokola S, Kuitunen H, Turpeenniemi‐Hujanen T, Kuittinen O. Significance of bulky mass and residual tumor – treated with or without con-solidative radiotherapy – to the risk of relapse in DLBCL patients. Cancer Med. 2020;9:1966–77.

https://doi.org/10.1002/cam4.2798 DOI: https://doi.org/10.1002/cam4.2798

Cook MB, McGlynn KA, Devesa SS, Freedman ND, Anderson WF. Sex disparities in cancer mortality and survival. Cancer Epidemiol Bi-omarkers Prev. 2011;20:1629–37.

https://doi.org/10.1158/1055-9965.EPI-11-0246 DOI: https://doi.org/10.1158/1055-9965.EPI-11-0246

Radkiewicz C, Bruchfeld JB, Weibull CE, Jeppesen ML, Frederiksen H, Lambe M, et al. Sex differences in lymphoma incidence and mortality by subtype: a population‐based study. Am J Hematol. 2023;98:23–30.

https://doi.org/10.1002/ajh.26744 DOI: https://doi.org/10.1002/ajh.26744

Durmaz M, Visser O, Posthuma EFM, Brouwer RE, Issa DE, De Jong D, et al. Time trends in primary therapy and relative survival of diffuse large B-cell lymphoma by stage: a nationwide, population-based study in the Netherlands, 1989–2018. Blood Cancer J. 2022;12:38.

https://doi.org/10.1038/s41408-022-00637-1 DOI: https://doi.org/10.1038/s41408-022-00637-1

Rock CB, Chipman JJ, Parsons MW, Weil CR, Hutten RJ, Tao R, et al. Second primary malignancies in diffuse large B-cell lymphoma survivors with 40 years of follow up: influence of chemotherapy and radiation therapy. Adv Radiat Oncol. 2022;7:101035.

https://doi.org/10.1016/j.adro.2022.101035 DOI: https://doi.org/10.1016/j.adro.2022.101035

Tao L, Clarke CA, Rosenberg AS, Advani RH, Jonas BA, Flowers CR, et al. Subsequent primary malignancies after diffuse large B‐cell lym-phoma in the modern treatment era. Br J Haematol. 2017;178:72–80.

https://doi.org/10.1111/bjh.14638 DOI: https://doi.org/10.1111/bjh.14638

Major A, Smith DE, Ghosh D, Rabinovitch R, Kamdar M. Risk and subtypes of secondary primary malignancies in diffuse large B‐cell lym-phoma survivors change over time based on stage at diagnosis. Cancer. 2020;126:189–201.

https://doi.org/10.1002/cncr.32513 DOI: https://doi.org/10.1002/cncr.32513

Kaprio E, Prusila R, Tokola S, Kuusisto MEL, Jantunen E, Kuitunen H, et al. Drug‐induced pneumonitis risk in diffuse large B‐cell/follicular lymphoma patients treated with R‐CHOP‐like regimen is associated with the use of granulocyte colony‐stimulating growth factors. Cancer Med. 2024;13:e6898.

https://doi.org/10.1002/cam4.6898 DOI: https://doi.org/10.1002/cam4.6898

Ekels A, Oerlemans S, Schagen SB, Issa DE, Thielen N, Nijziel MR, et al. The course of self-perceived cognitive functioning among patients with lymphoma and the co-occurrence with fatigue and psychological distress. J Cancer Surviv. 2025;19(1):183–96.

https://doi.org/10.1007/s11764-023-01458-2 DOI: https://doi.org/10.1007/s11764-023-01458-2

Krolak D, Collins B, Weiss L, Harris C, Van Der Jagt R. Cognitive function and its relationship to other psychosocial factors in lymphoma survivors. Support Care Cancer. 2017;25:905–13.

https://doi.org/10.1007/s00520-016-3480-z DOI: https://doi.org/10.1007/s00520-016-3480-z

Mariegaard J, Wenstrup J, Lim KZM, Bidstrup PE, Von Heymann A, Johansen C, et al. Prevalence of cognitive impairment and its relation to mental health in Danish lymphoma survivors. Support Care Cancer. 2021;29:3319–28.

https://doi.org/10.1007/s00520-020-05857-4 DOI: https://doi.org/10.1007/s00520-020-05857-4

Baech J, Severinsen MT, Øvlisen AK, Frederiksen H, Vestergaard P, Torp-Pedersen C, et al. Risk of diabetes and the impact on preexisting diabetes in patients with lymphoma treated with steroid-containing immunochemotherapy. Blood Adv. 2022;6:4427–35.

https://doi.org/10.1182/bloodadvances.2021006859 DOI: https://doi.org/10.1182/bloodadvances.2021006859

Laugesen K, Ludvigsson JF, Schmidt M, Gissler M, Valdimarsdottir UA, Lunde A, et al. Nordic health registry-based research: a review of health care systems and key registries. CLEP. 2021;13:533–54.

https://doi.org/10.2147/CLEP.S314959 DOI: https://doi.org/10.2147/CLEP.S314959

Keskimaki I, Tynkkynen L-K, Reissell E, Koivusalo M, Syrja V, Vuorenkoski L, et al. Finland: health system review. Health Syst Transit. 2019;21:1–166.

Additional Files

Published

2025-02-25

How to Cite

Anttalainen, A., Ukkola-Vuoti, L., Vihervaara, V., Silvola, S., & Kuittinen, O. (2025). Population based registry study on large B-cell lymphoma mortality and morbidity in Finland. Acta Oncologica, 64, 303–311. https://doi.org/10.2340/1651-226X.2025.42539

Issue

Section

Original article

Categories