BACKGROUND: Chronic lymphocytic leukemia (CLL) is a common hematological malignancy with highly variable clinical presentation. Many patients never require any treatment but for the others, chemotherapy, immunochemotherapy, and newer targeted therapies have changed the treatment landscape. Diagnostic age influences the applied treatment, and we thus wanted to analyze age-specific survival trends through 50 years up to 2020s. METHODS: We used 1- and 5-year relative survival from the NORDCAN database, with data from Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE). Because of the variable presentation of CLL, we also considered incidence and mortality trends. For comparison, US SEER data were used. RESULTS: The large age-specific survival differences in 1972-76 almost disappeared by 2017-21. While 5-year survival in younger patients exceeded 90%, for those diagnosed at age 80-89 years, survival reached 90% in DK and SE women, 80% in NO and SE men, but only 50% in FI. DK 5-year overall survival for men was 92.4%, and for women, it was 96.3%. These survival figures were higher than age-group-specific US survival data. CONCLUSIONS: The DK data are probably global top figures for national survival which could be achieved by boosting survival even among the oldest patients. The qualification to these figures and international comparisons is that survival needs to be considered in terms of incidence, which is high in DK and NO. Low survival of the FI 80-89-year-old patients, even in the first year after diagnosis, may suggest delayed diagnosis, which should call for a closer national scrutiny.

Biomedical Center Faculty of Medicine Charles University 323 00 Pilsen Czech Republic

Cancer Gene Therapy Group Translational Immunology Research Program University of Helsinki 00014 Helsinki Finland

Comprehensive Cancer Center Helsinki University Hospital 00290 Helsinki Finland

Department of Clinical Pharmacology HUS Diagnostic Center Helsinki University Hospital 00014 Helsinki Finland

Department of Clinical Pharmacology University of Helsinki 00014 Helsinki Finland

Department of Hematology Helsinki University Hospital Comprehensive Cancer Center 00029 Helsinki Finland

Department of Hematology Rigshospitalet Copenhagen University Hospital 2100 Copenhagen Denmark

Department of Hematology Stem Cell Center Skåne University Hospital Lund Department of Laboratory Medicine Lund University SE 221 84 Lund Sweden

Division of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld 580 69120 Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center 72076 Heidelberg Germany

Hopp Children's Cancer Center 69120 Heidelberg Germany

Individualized Drug Therapy Research Program Faculty of Medicine University of Helsinki 00014 Helsinki Finland

Zobrazit více v PubMed

Burger J.A. Treatment of Chronic Lymphocytic Leukemia. N. Engl. J. Med. 2020;383:460–473. doi: 10.1056/NEJMra1908213. PubMed DOI

Koehrer S., Burger J.A. Chronic Lymphocytic Leukemia: Disease Biology. Acta Haematol. 2024;147:8–21. doi: 10.1159/000533610. PubMed DOI PMC

DeVita V.T., Jr., Chu E. A history of cancer chemotherapy. Cancer Res. 2008;68:8643–8653. doi: 10.1158/0008-5472.CAN-07-6611. PubMed DOI

da Cunha-Bang C., Simonsen J., Rostgaard K., Geisler C., Hjalgrim H., Niemann C.U. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: A Danish population-based study of 10455 patients. Blood Cancer J. 2016;6:e499. doi: 10.1038/bcj.2016.105. PubMed DOI PMC

Eichhorst B., Hallek M., Dreyling M. Chronic lymphocytic leukemia: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann. Oncol. 2008;19((Suppl. S2)):ii60–ii62. doi: 10.1093/annonc/mdn090. PubMed DOI

Eichhorst B., Robak T., Montserrat E., Ghia P., Niemann C.U., Kater A.P., Gregor M., Cymbalista F., Buske C., Hillmen P., et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2021;32:23–33. doi: 10.1016/j.annonc.2020.09.019. PubMed DOI

Eichhorst B., Niemann C.U., Kater A.P., Fürstenau M., von Tresckow J., Zhang C., Robrecht S., Gregor M., Juliusson G., Thornton P., et al. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. N. Engl. J. Med. 2023;388:1739–1754. doi: 10.1056/NEJMoa2213093. PubMed DOI

Rotbain E.C., Niemann C.U., Rostgaard K., da Cunha-Bang C., Hjalgrim H., Frederiksen H. Mapping comorbidity in chronic lymphocytic leukemia: Impact of individual comorbidities on treatment, mortality, and causes of death. Leukemia. 2021;35:2570–2580. doi: 10.1038/s41375-021-01156-x. PubMed DOI

Brieghel C., Galle V., Agius R., da Cunha-Bang C., Andersen M.A., Vlummens P., Mattsson M., Rosenquist R., Smedby K.E., Herling C.D., et al. Identifying patients with chronic lymphocytic leukemia without need of treatment: End of endless watch and wait? Eur. J. Haematol. 2022;108:369–378. doi: 10.1111/ejh.13743. PubMed DOI

Rotbain E.C., da Cunha-Bang C., Brieghel C., Niemann C.U. CLL-IPI applied in Binet A CLL: A nationwide cohort study. Blood Adv. 2022;6:5698–5701. doi: 10.1182/bloodadvances.2021006259. PubMed DOI PMC

Andersen M.A., Eriksen C.T., Brieghel C., Biccler J.L., Cunha-Bang C.D., Helleberg M., Niemann C.U. Incidence and predictors of infection among patients prior to treatment of chronic lymphocytic leukemia: A Danish nationwide cohort study. Haematologica. 2018;103:e300–e303. doi: 10.3324/haematol.2017.182006. PubMed DOI PMC

Andersen M.A., Moser C.E., Lundgren J., Niemann C.U. Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: A longitudinal nation-wide cohort study. Leukemia. 2019;33:662–670. doi: 10.1038/s41375-018-0316-5. PubMed DOI

Andersen M.A., Niemann C.U. Immune failure, infection and survival in chronic lymphocytic leukemia in Denmark. Haematologica. 2018;103:e330. doi: 10.3324/haematol.2018.197889. PubMed DOI PMC

Andersen M.A., Niemann C.U., Rostgaard K., Dalby T., Sørrig R., Weinberger D.M., Hjalgrim H., Harboe Z.B. Differences and Temporal Changes in Risk of Invasive Pneumococcal Disease in Adults with Hematological Malignancies: Results from a Nationwide 16-Year Cohort Study. Clin. Infect. Dis. 2021;72:463–471. doi: 10.1093/cid/ciaa090. PubMed DOI PMC

Guarana M., Nucci M. Infections in patients with chronic lymphocytic leukemia. Hematol. Transfus. Cell Ther. 2023;45:387–393. doi: 10.1016/j.htct.2023.05.006. PubMed DOI PMC

Cordoba R., Eyre T.A., Klepin H.D., Wildes T.M., Goede V. A comprehensive approach to therapy of haematological malignancies in older patients. Lancet. Haematol. 2021;8:e840–e852. doi: 10.1016/S2352-3026(21)00241-6. PubMed DOI

Agius R., Brieghel C., Andersen M.A., Pearson A.T., Ledergerber B., Cozzi-Lepri A., Louzoun Y., Andersen C.L., Bergstedt J., von Stemann J.H., et al. Machine learning can identify newly diagnosed patients with CLL at high risk of infection. Nat. Commun. 2020;11:363. doi: 10.1038/s41467-019-14225-8. PubMed DOI PMC

Steingrímsson V., Gíslason G.K., Aspelund T., Turesson I., Björkholm M., Landgren O., Kristinsson S.Y. A population-based study on serious inpatient bacterial infections in patients with chronic lymphocytic leukemia and their impact on survival. Eur. J. Haematol. 2020;105:547–554. doi: 10.1111/ejh.13477. PubMed DOI

Pleyer C., Sun C., Desai S., Ahn I.E., Tian X., Nierman P., Soto S., Superata J., Valdez J., Lotter J., et al. Reconstitution of humoral immunity and decreased risk of infections in patients with chronic lymphocytic leukemia treated with Bruton tyrosine kinase inhibitors. Leuk. Lymphoma. 2020;61:2375–2382. doi: 10.1080/10428194.2020.1772477. PubMed DOI PMC

Aarup K., Rotbain E.C., Enggaard L., Pedersen R.S., Bergmann O.J., Thomsen R.H., Frederiksen M., Frederiksen H., Nielsen T., Christiansen I., et al. Real-world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib. Eur. J. Haematol. 2020;105:646–654. doi: 10.1111/ejh.13499. PubMed DOI

Vainer N., Aarup K., Andersen M.A., Wind-Hansen L., Nielsen T., Frederiksen H., Enggaard L., Poulsen C.B., Niemann C.U., Rotbain E.C. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br. J. Haematol. 2023;201:874–886. doi: 10.1111/bjh.18715. PubMed DOI

De Angelis R., Minicozzi P., Sant M., Dal Maso L., Brewster D.H., Osca-Gelis G., Visser O., Maynadié M., Marcos-Gragera R., Troussard X., et al. Survival variations by country and age for lymphoid and myeloid malignancies in Europe 2000–2007: Results of EUROCARE-5 population-based study. Eur. J. Cancer. 2015;51:2254–2268. doi: 10.1016/j.ejca.2015.08.003. PubMed DOI

Sant M., Minicozzi P., Mounier M., Anderson L.A., Brenner H., Holleczek B., Marcos-Gragera R., Maynadié M., Monnereau A., Osca-Gelis G., et al. Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: Results of EUROCARE-5, a population-based study. Lancet Oncol. 2014;15:931–942. doi: 10.1016/S1470-2045(14)70282-7. PubMed DOI

Pulte D., Jansen L., Brenner H. Changes in long term survival after diagnosis with common hematologic malignancies in the early 21st century. Blood Cancer J. 2020;10:56. doi: 10.1038/s41408-020-0323-4. PubMed DOI PMC

Alrawashdh N., Sweasy J., Erstad B., McBride A., Persky D.O., Abraham I. Survival trends in chronic lymphocytic leukemia across treatment eras: US SEER database analysis (1985–2017) Ann. Hematol. 2021;100:2501–2512. doi: 10.1007/s00277-021-04600-1. PubMed DOI

Andres M., Feller A., Arndt V., The NICER Working Group Trends of incidence, mortality and survival for chronic lymphocytic leukaemia / small lymphocytic lymphoma in Switzerland between 1997 and 2016: A population-based study. Swiss Med. Wkly. 2021;151:w20463. doi: 10.4414/smw.2021.20463. PubMed DOI

van der Straten L., Levin M.D., Visser O., Posthuma E.F.M., Doorduijn J.K., Kater A.P., Dinmohamed A.G. Survival continues to increase in chronic lymphocytic leukaemia: A population-based analysis among 20,468 patients diagnosed in the Netherlands between 1989 and 2016. Br. J. Haematol. 2020;189:574–577. doi: 10.1111/bjh.16397. PubMed DOI

Pukkala E., Engholm G., Hojsgaard Schmidt L.K., Storm H., Khan S., Lambe M., Pettersson D., Olafsdottir E., Tryggvadottir L., Hakanen T., et al. Nordic Cancer Registries—An overview of their procedures and data comparability. Acta Oncol. 2018;57:440–455. doi: 10.1080/0284186X.2017.1407039. PubMed DOI

Engholm G., Ferlay J., Christensen N., Bray F., Gjerstorff M.L., Klint A., Køtlum J.E., Olafsdóttir E., Pukkala E., Storm H.H. NORDCAN--a Nordic tool for cancer information, planning, quality control and research. Acta Oncol. 2010;49:725–736. doi: 10.3109/02841861003782017. PubMed DOI

Larønningen S.A.G., Bray F., Engholm G., Ervik M., Guðmundsdóttir E.M., Gulbrandsen J., Hansen H.L., Hansen H.M., Johannesen T.B., Kristensen S., et al. NORDCAN: Cancer Incidence, Mortality, Prevalence and Survival in the Nordic Countries, Version 9.3. International Agency for Research on Cancer, World Health Organization; Lyon, France: 2023.

Hemminki K., Försti A., Hansson M. Incidence, mortality and survival in multiple myeloma compared to other hematopoietic neoplasms in Sweden up to year 2016. Sci. Rep. 2021;11:17272. doi: 10.1038/s41598-021-96804-8. PubMed DOI PMC

Storm H.H., Klint A., Tryggvadottir L., Gislum M., Engholm G., Bray F., Hakulinen T. Trends in the survival of patients diagnosed with malignant neoplasms of lymphoid, haematopoietic, and related tissue in the Nordic countries 1964–2003 followed up to the end of 2006. Acta Oncol. 2010;49:694–712. doi: 10.3109/02841861003631495. PubMed DOI

Hemminki K., Hemminki J., Försti A., Sud A. Survival trends in hematological malignancies in the Nordic countries through 50 years. Blood Cancer J. 2022;7:150. doi: 10.1038/s41408-022-00728-z. PubMed DOI PMC

Lenartova A., Johannesen T.B., Tjønnfjord G.E. National trends in incidence and survival of chronic lymphocytic leukemia in Norway for 1953–2012: A systematic analysis of population-based data. Cancer Med. 2016;5:3588–3595. doi: 10.1002/cam4.849. PubMed DOI PMC

Sylvan S.E., Asklid A., Johansson H., Klintman J., Bjellvi J., Tolvgård S., Kimby E., Norin S., Andersson P.O., Karlsson C., et al. First-line therapy in chronic lymphocytic leukemia: A Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013. Haematologica. 2019;104:797–804. doi: 10.3324/haematol.2018.200204. PubMed DOI PMC

Lindström V., Hakkarainen K.M., Mehtälä J., Klement R., Leval A., Järvinen T.M. Observational evidence from patients diagnosed with chronic lymphocytic leukaemia (CLL) in Finland between 2005–2015 show improved survival over time. Eur. J. Haematol. 2019;103:190–199. doi: 10.1111/ejh.13273. PubMed DOI PMC

da Cunha-Bang C., Christiansen I., Niemann C.U. The CLL-IPI applied in a population-based cohort. Blood. 2016;128:2181–2183. doi: 10.1182/blood-2016-07-724740. PubMed DOI

Ji J., Sundquist K., Sundquist J., Hemminki K. Comparability of cancer identification among Death Registry, Cancer Registry and Hospital Discharge Registry. Int. J. Cancer. 2012;131:2085–2093. doi: 10.1002/ijc.27462. PubMed DOI

Lundberg F.E., Andersson T.M., Lambe M., Engholm G., Mørch L.S., Johannesen T.B., Virtanen A., Pettersson D., Ólafsdóttir E.J., Birgisson H., et al. Trends in cancer survival in the Nordic countries 1990–2016: The NORDCAN survival studies. Acta Oncol. 2020;59:1266–1274. doi: 10.1080/0284186X.2020.1822544. PubMed DOI

Brenner H., Arndt V., Gefeller O., Hakulinen T. An alternative approach to age adjustment of cancer survival rates. Eur. J. Cancer. 2004;40:2317–2322. doi: 10.1016/j.ejca.2004.07.007. PubMed DOI

Tichanek F., Försti A., Liska V., Hemminki A., Hemminki K. Survival in Colon, Rectal and Small Intestinal Cancers in the Nordic Countries through a Half Century. Cancers. 2023;15:991. doi: 10.3390/cancers15030991. PubMed DOI PMC

Lamb M., Painter D., Howell D., Barrans S., Cargo C., de Tute R., Tooze R., Burton C., Patmore R., Roman E., et al. Lymphoid blood cancers, incidence and survival 2005–2023: A report from the UK’s Haematological Malignancy Research Network. Cancer Epidemiol. 2024;88:102513. doi: 10.1016/j.canep.2023.102513. PubMed DOI

Rotbain E.C., Frederiksen H., Hjalgrim H., Rostgaard K., Egholm G.J., Zahedi B., Poulsen C.B., Enggard L., da Cunha-Bang C., Niemann C.U. IGHV mutational status and outcome for patients with chronic lymphocytic leukemia upon treatment: A Danish nationwide population-based study. Haematologica. 2020;105:1621–1629. doi: 10.3324/haematol.2019.220194. PubMed DOI PMC

Faitová T., Brieghel C., Eriksson F., Niemann C.U. Mortality in patients with lymphoid malignancies and multiple myeloma was stable upon and during the COVID-19 pandemic: A population-based, nation-wide study. Hemasphere. 2024;8:e57. doi: 10.1002/hem3.57. PubMed DOI PMC

Ranti J., Perkonoja K., Kauko T., Loponen H., Joensuu E.I., Järvinen T.M. Characterization of real-world treatment practices and outcomes among patients with chronic lymphocytic leukemia treated in a Finnish tertiary center. EJHaem. 2022;3:291–300. doi: 10.1002/jha2.322. PubMed DOI PMC

Hemminki K., Zitricky F., Försti A., Kontro M., Gjertsen B.T., Severinsen M.T., Juliusson G. Age-specific survival in acute myeloid leukemia in the Nordic countries through a half century. Blood Cancer J. 2024;14:44. doi: 10.1038/s41408-024-01033-7. PubMed DOI PMC

Hemminki K., Zitricky F., Försti A., Silvennoinen R., Vangsted A., Hansson M. Large differencies in age-specific survival in multiple myeloma in the nordic countries. Blood Cancer J. 2024;14:43. doi: 10.1038/s41408-024-01026-6. PubMed DOI PMC

Probst H.B., Hussain Z.B., Andersen O. Cancer patient pathways in Denmark as a joint effort between bureaucrats, health professionals and politicians—A national Danish project. Health Policy. 2012;105:65–70. doi: 10.1016/j.healthpol.2011.11.001. PubMed DOI