Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients


To determine the risk of a wide range of second malignancies in patients with myeloproliferative neoplasms (MPNs), we conducted a large population-based study and compared the results to matched controls. From national Swedish registers, 9379 patients with MPNs diagnosed between 1973 and 2009, and 35,682 matched controls were identified as well as information on second malignancies, with follow-up until 2010. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using Cox regression and a flexible parametric model. There was a significantly increased risk of any non-hematologic cancer with HR of 1.6 (95% CI: 1.5–1.7). The HRs for non-melanoma skin cancer was 2.8 (2.4–3.3), kidney cancer 2.8 (2.0–4.0), brain cancer 2.8 (1.9–4.2), endocrine cancers 2.5 (1.6–3.8), malignant melanoma 1.9 (1.4–2.7), pancreas cancer 1.8 (1.2–2.6), lung cancer 1.7 (1.4–2.2), and head and neck cancer 1.7 (1.2–2.6). The HR of second malignancies was similar across all MPN subtypes, sex, and calendar periods of MPN diagnosis. The risk of developing a hematologic malignancy was also significantly increased; the HR for acute myeloid leukemia was 46.0 (32.6–64.9) and for lymphoma 2.6 (2.0–3.3). In conclusion, our study provides robust population-based support of an increased cancer risk in MPN patients.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Swerdlow SH, International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer; 2008. p. 439.

    Google Scholar 

  2. Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29:761–70.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hultcrantz M, Kristinsson SY, Andersson TM, Landgren O, Eloranta S, Derolf AR, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. J Clin Oncol. 2012;30:2995–3001.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124:2507–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29:3179–84.

    Article  PubMed  Google Scholar 

  6. Vannucchi AM, Masala G, Antonioli E, Chiara Susini M, Guglielmelli P, Pieri L, et al. Increased risk of lymphoid neoplasms in patients with Philadelphia chromosome-negative myeloproliferative neoplasms. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive. Oncology. 2009;18:2068–73.

    CAS  Google Scholar 

  7. Rumi E, Passamonti F, Elena C, Pietra D, Arcaini L, Astori C, et al. Increased risk of lymphoid neoplasm in patients with myeloproliferative neoplasm: a study of 1,915 patients. Haematologica. 2011;96:454–8.

    Article  PubMed  Google Scholar 

  8. Masarova L, Newberry KJ, Pierce SA, Estrov Z, Cortes JE, Kantarjian HM, et al. Association of lymphoid malignancies and Philadelphia-chromosome negative myeloproliferative neoplasms: clinical characteristics, therapy and outcome. Leuk Res. 2015;39:822–7.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kissova J, Ovesna P, Penka M, Bulikova A, Kiss I. Second malignancies in philadelphia-negative myeloproliferative neoplasms-single-center experience. Anticancer Res. 2014;34:2489–96.

    PubMed  Google Scholar 

  10. Frederiksen H, Farkas DK, Christiansen CF, Hasselbalch HC, Sorensen HT. Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study. Blood. 2011;118:6515–20.

    Article  CAS  PubMed  Google Scholar 

  11. Khanal N, Giri S, Upadhyay S, Shostrom VK, Pathak R, Bhatt VR. Risk of second primary malignancies and survival of adult patients with polycythemia vera: A United States population-based retrospective study. Leuk Lymphoma. 2016;57:129–33.

    Article  CAS  PubMed  Google Scholar 

  12. Fallah M, Kharazmi E, Sundquist J, Hemminki K. Higher risk of primary cancers after polycythaemia vera and vice versa. Br J Haematol. 2011;153:283–5.

    Article  PubMed  Google Scholar 

  13. Masarova L, Cherry M, Newberry KJ, Estrov Z, Cortes JE, Kantarjian HM, et al. Secondary solid tumors and lymphoma in patients with essential thrombocythemia and polycythemia vera - single center experience. Leuk Lymphoma. 2016;57:237–9.

    Article  PubMed  Google Scholar 

  14. Susini MC, Masala G, Antonioli E, Pieri L, Guglielmelli P, Palli D, et al. Risk of second cancers in chronic myeloproliferative neoplasms. Blood. 2012;119:3861–2.

    Article  CAS  PubMed  Google Scholar 

  15. Andreasson B, Lofvenberg E, Westin J. Management of patients with polycythaemia vera: results of a survey among Swedish haematologists. Eur J Haematol. 2005;74:489–95.

    Article  PubMed  Google Scholar 

  16. Berlin NI. Diagnosis and classification of the polycythemias. Semin Hematol. 1975;12:339–51.

    CAS  PubMed  Google Scholar 

  17. Barlow L, Westergren K, Holmberg L, Talback M. The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol. 2009;48:27–33.

    Article  PubMed  Google Scholar 

  18. Turesson I, Linet MS, Bjorkholm M, Kristinsson SY, Goldin LR, Caporaso NE, et al. Ascertainment and diagnostic accuracy for hematopoietic lymphoproliferative malignancies in Sweden 1964-2003. Int J Cancer. 2007;121:2260–6.

    Article  CAS  PubMed  Google Scholar 

  19. Najean Y. Association of renal carcinoma and polycythemia vera: 5 cases in which nephrectomy preceded and did not influence the clinical course of the polycythemia. Nouv Rev Fr d’hematologie. 1991;33:9–10.

    CAS  Google Scholar 

  20. Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5:e366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Miltiades P, Lamprianidou E, Kerzeli IK, Nakou E, Papamichos SI, Spanoudakis E, et al. Three-fold higher frequency of circulating chronic lymphocytic leukemia-like B-cell clones in patients with Ph-myeloproliferative neoplasms. Leuk Res. 2015;39:1159–1165.

    Article  Google Scholar 

  22. Laurenti L, Tarnani M, Nichele I, Ciolli S, Cortelezzi A, Forconi F, et al. The coexistence of chronic lymphocytic leukemia and myeloproliperative neoplasms: a retrospective multicentric GIMEMA experience. Am J Hematol. 2011;86:1007–12.

    Article  PubMed  Google Scholar 

  23. Nordic MPN Study Group. Nordic care program for patients with essential thrombocythemia, polycythemia vera and primary myelofibrosis. 2017. Accessed 1 Feb 2018.

  24. Saraceno R, Teoli M, Chimenti S. Hydroxyurea associated with concomitant occurrence of diffuse longitudinal melanonychia and multiple squamous cell carcinomas in an elderly subject. Clin Ther. 2008;30:1324–9.

    Article  CAS  PubMed  Google Scholar 

  25. Wiechert A, Reinhard G, Tuting T, Uerlich M, Bieber T, Wenzel J. Multiple skin cancers in a patient treated with hydroxyurea. Hautarzt. 2009;60:651–2. 4

    Article  CAS  PubMed  Google Scholar 

  26. Turner ML. Sun, drugs, and skin cancer: a continuing saga. Arch Dermatol. 2010;146:329–31.

    Article  PubMed  Google Scholar 

  27. Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123:2220–8.

    Article  CAS  PubMed  Google Scholar 

  28. Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129:667–79.

    Article  CAS  PubMed  Google Scholar 

  29. Bian EB, Zong G, Xie YS, Meng XM, Huang C, Li J, et al. TET family proteins: new players in gliomas. J Neurooncol. 2014;116:429–35.

    Article  CAS  PubMed  Google Scholar 

  30. Song F, Amos CI, Lee JE, Lian CG, Fang S, Liu H, et al. Identification of a melanoma susceptibility locus and somatic mutation in TET2. Carcinogenesis. 2014;35:2097–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nicolas CS, Amici M, Bortolotto ZA, Doherty A, Csaba Z, Fafouri A, et al. The role of JAK-STAT signaling within the CNS. Jak-Stat . 2013;2:e22925.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Katoh M. Functional and cancer genomics of ASXL family members. Br J Cancer. 2013;109:299–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. De Filippi P, Zecca M, Lisini D, Rosti V, Cagioni C, Carlo-Stella C, et al. Germline mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia. Br J Haematol. 2009;147:706–9.

    Article  PubMed  Google Scholar 

  34. Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, et al. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. J Med Genet. 2010;47:421–8.

    Article  CAS  PubMed  Google Scholar 

  35. Schaub FX, Looser R, Li S, Hao-Shen H, Lehmann T, Tichelli A, et al. Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood. 2010;115:2003–7.

    Article  CAS  PubMed  Google Scholar 

  36. Pettersson H, Knutsen H, Holmberg E, Andreasson B. Increased incidence of another cancer in myeloproliferative neoplasms patients at the time of diagnosis. Eur J Haematol. 2015;94:152–6.

    Article  PubMed  Google Scholar 

  37. Landgren O, Goldin LR, Kristinsson SY, Helgadottir EA, Samuelsson J, Bjorkholm M. Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24,577 first-degree relatives of 11,039 patients with myeloproliferative neoplasms in Sweden. Blood. 2008;112:2199–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jaffe ES, World Health Organization. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon, Oxford: IARC Press; Oxford University Press; 2001. p. 351.

    Google Scholar 

Download references


We thank the “Swedish Initiative for research on Microdata in the Social and Medical sciences” (SIMSAM) and Rozita Broumandi for valuable assistance in collecting the information from the Swedish registers.

Author contributions

Conception and design: ARL, HB, TM-LA, MH. Collection and assembly of data: ARL, HB, TM-LA, PWD, MB, SYK, MH. Data analysis and interpretation: All authors. Manuscript writing: All authors. Final approval of manuscript: All authors. Research funding: The regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, Blodcancerfonden, The Cancer Research Foundations of Radiumhemmet, The Adolf H. Lundin Charitable Foundation, The Memorial Sloan Kettering Core Grant (P30 CA008748), Swedish Cancer Society.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Anna Ravn Landtblom.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

This study was previously presented in part as an oral contribution at European Hematology Association 21st Congress 10th June, 2016 Copenhagen, Denmark.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Landtblom, A.R., Bower, H., Andersson, T.ML. et al. Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients. Leukemia 32, 2203–2210 (2018).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links