Skip to main content

Thank you for visiting nature.com. 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.

  • Original Article
  • Published:

Chronic lymphocytic leukemia

Risk of non-hematologic cancer in individuals with high-count monoclonal B-cell lymphocytosis

Leukemia volume 30, pages 331–336 (2016)Cite this article

Subjects

Abstract

It is unknown whether individuals with monoclonal B-cell lymphocytosis (MBL) are at risk for adverse outcomes associated with chronic lymphocytic leukemia (CLL), such as the risk of non-hematologic cancer. We identified all locally residing individuals diagnosed with high-count MBL at Mayo Clinic between 1999 and 2009 and compared their rates of non-hematologic cancer with that of patients with CLL and two control cohorts: general medicine patients and patients who underwent clinical evaluation with flow cytometry but who had no hematologic malignancy. After excluding individuals with prior cancers, there were 107 high-count MBL cases, 132 CLL cases, 589 clinic controls and 482 flow cytometry controls. With 4.6 years median follow-up, 14 (13%) individuals with high-count MBL, 21 (4%) clinic controls (comparison MBL P<0.0001), 18 (4%) flow controls (comparison MBL P=0.0001) and 16 (12%) CLL patients (comparison MBL P=0.82) developed non-hematologic cancer. On multivariable Cox regression analysis, individuals with high-count MBL had higher risk of non-hematologic cancer compared with flow controls (hazard ratio (HR)=2.36; P=0.04) and borderline higher risk compared with clinic controls (HR=2.00; P=0.07). Patients with high-count MBL appear to be at increased risk for non-hematologic cancer, further reinforcing that high-count MBL has a distinct clinical phenotype despite low risk of progression to CLL.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. Call TG, Phyliky RL, Noel P, Habermann TM, Beard CM, O'Fallon WM et al. Incidence of chronic lymphocytic leukemia in Olmsted County, Minnesota, 1935 through 1989, with emphasis on changes in initial stage at diagnosis. Mayo Clin Proc 1994; 69: 323–328.

    Article  CAS  PubMed  Google Scholar 

  2. Hisada M, Biggar RJ, Greene MH, Fraumeni JF Jr, Travis LB . Solid tumors after chronic lymphocytic leukemia. Blood 2001; 98: 1979–1981.

    Article  CAS  PubMed  Google Scholar 

  3. Morton LM, Curtis RE, Linet MS, Bluhm EC, Tucker MA, Caporaso N et al. Second malignancy risks after non-Hodgkin's lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol 2010; 28: 4935–4944.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tsimberidou AM, Wen S, McLaughlin P, O'Brien S, Wierda WG, Lerner S et al. Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol 2009; 27: 904–910.

    Article  PubMed  Google Scholar 

  5. Manusow D, Weinerman BH . Subsequent neoplasia in chronic lymphocytic leukemia. JAMA 1975; 232: 267–269.

    Article  CAS  PubMed  Google Scholar 

  6. Maddocks-Christianson K, Slager SL, Zent CS, Reinalda M, Call TG, Habermann TM et al. Risk factors for development of a second lymphoid malignancy in patients with chronic lymphocytic leukaemia. Br J Haematol 2007; 139: 398–404.

    Article  PubMed  Google Scholar 

  7. Schollkopf C, Rosendahl D, Rostgaard K, Pipper C, Hjalgrim H . Risk of second cancer after chronic lymphocytic leukemia. Int J Cancer 2007; 121: 151–156.

    Article  CAS  PubMed  Google Scholar 

  8. Solomon BM, Rabe KG, Slager SL, Brewer JD, Cerhan JR, Shanafelt TD . Overall and cancer-specific survival of patients with breast, colon, kidney, and lung cancers with and without chronic lymphocytic leukemia: a SEER population-based study. J Clin Oncol 2013; 31: 930–937.

    Article  PubMed  Google Scholar 

  9. Marti GE, Rawstron AC, Ghia P, Hillmen P, Houlston RS, Kay N et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol 2005; 130: 325–332.

    Article  PubMed  Google Scholar 

  10. Fazi C, Scarfo L, Pecciarini L, Cottini F, Dagklis A, Janus A et al. General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL. Blood 2011; 118: 6618–6625.

    Article  CAS  PubMed  Google Scholar 

  11. Ghia P, Prato G, Scielzo C, Stella S, Geuna M, Guida G et al. Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood 2004; 103: 2337–2342.

    Article  CAS  PubMed  Google Scholar 

  12. Rawstron AC, Bennett FL, O'Connor SJ, Kwok M, Fenton JA, Plummer M et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med 2008; 359: 575–583.

    Article  CAS  PubMed  Google Scholar 

  13. Rawstron AC, Green MJ, Kuzmicki A, Kennedy B, Fenton JA, Evans PA et al. Monoclonal B lymphocytes with the characteristics of ‘indolent’ chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts. Blood 2002; 100: 635–639.

    Article  CAS  PubMed  Google Scholar 

  14. Shanafelt TD, Ghia P, Lanasa MC, Landgren O, Rawstron AC . Monoclonal B-cell lymphocytosis (MBL): biology, natural history and clinical management. Leukemia 2010; 24: 512–520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shanafelt TD, Kay NE, Rabe KG, Call TG, Zent CS, Maddocks K et al. Brief report: natural history of individuals with clinically recognized monoclonal B-cell lymphocytosis compared with patients with Rai 0 chronic lymphocytic leukemia. J Clin Oncol 2009; 27: 3959–3963.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Moreira J, Rabe KG, Cerhan JR, Kay NE, Wilson JW, Call TG et al. Infectious complications among individuals with clinical Monoclonal B-cell Lymphocytosis (MBL): a cohort study of newly diagnosed cases compared to controls. Leukemia 2012; 27: 136–141.

    Article  PubMed  Google Scholar 

  17. Thurmes P, Call T, Slager S, Zent C, Jenkins G, Schwager S et al. Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocytic leukemia. Leuk Lymphoma 2008; 49: 49–56.

    Article  PubMed  Google Scholar 

  18. Cerhan JR, Fredericksen ZS, Wang AH, Habermann TM, Kay NE, Macon WR et al. Design and validity of a clinic-based case-control study on the molecular epidemiology of lymphoma. Int J Mol Epidemiol Genet 2011; 2: 95–113.

    PubMed  PubMed Central  Google Scholar 

  19. Gooley T, Leisenring W, Crowely J, Storer B . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.

    Article  CAS  PubMed  Google Scholar 

  20. Gray R . A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141–1154.

    Article  Google Scholar 

  21. Fine J, Gray R . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

    Article  Google Scholar 

  22. Brewer JD, Shanafelt TD, Otley CC, Roenigk RK, Cerhan JR, Kay NE et al. Chronic lymphocytic leukemia decreases survival of patients with malignant melanoma and Merkel cell carcinoma in a SEER Population-Based Study. J Clin Oncol 2012; 30: 843–849.

    Article  PubMed  Google Scholar 

  23. Moyer VA . Screening for lung cancer: U.S. Preventative Services Task Force Recommendation Statement. Ann Intern Med 2014; 160: 330–338.

    PubMed  Google Scholar 

  24. Force USPST. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 151: 716–726, W-236.

    Article  Google Scholar 

  25. Force USPST. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008; 149: 627–637.

    Article  Google Scholar 

  26. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–4997.

    CAS  PubMed  Google Scholar 

  27. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero D, Dohner H et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446–5456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Scarfo L, Fazi C, Ghia P . MBL versus CLL: how important is the distinction? Hematol Oncol Clin North Am 2013; 27: 251–265.

    Article  PubMed  Google Scholar 

  29. Molica S, Mauro FR, Giannarelli D, Lauria F, Cortelezzi A, Brugiatelli M et al. Differentiating chronic lymphocytic leukemia from monoclonal B-lymphocytosis according to clinical outcome: on behalf of the GIMEMA chronic lymphoproliferative diseases working group. Haematologica 2011; 96: 277–283.

    Article  PubMed  Google Scholar 

  30. Shanafelt TD, Kay NE, Jenkins G, Call TG, Zent CS, Jelinek DF et al. B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome. Blood 2009; 113: 4188–4196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Shanafelt TD, Kay NE, Rabe KG, Call TG, Zent CS, Schwager SM et al. Survival of patients with clinically identified monoclonal B-cell lymphocytosis (MBL) relative to the age- and sex-matched general population. Leukemia 2012; 26: 373–376.

    Article  CAS  PubMed  Google Scholar 

  32. Mansfield AS, Rabe KG, Slager SL, Schwager SM, Call TG, Brewer JD et al. Skin cancer surveillance and malignancies of the skin in a community-dwelling cohort of patients with newly diagnosed chronic lymphocytic Leukemia. J Oncol Pract 2013; 10: e1–e4.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M et al. 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host. Clin Infect Dis 2013; 58: e44–100.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by R01 CA92153 and the Henry J Predolin Foundation. Dr Shanafelt is a Clinical Scholar of the Leukemia and Lymphoma Society.

Author information

Authors and Affiliations

  1. University of South Dakota Sanford School of Medicine, Vermillion, SD, USA

    B M Solomon

  2. Avera Medical Group Oncology and Hematology, Sioux, SD, USA

    B M Solomon

  3. Mayo Clinic Department of Health Sciences Research, Rochester, MN, USA

    K G Chaffee, J R Cerhan & S L Slager

  4. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    J Moreira

  5. Mayo Clinic Department of Medicine, Rochester, MN, USA

    S M Schwager, T G Call, N E Kay & T D Shanafelt

  6. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    S M Schwager, T G Call, N E Kay & T D Shanafelt

Authors
  1. B M Solomon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K G Chaffee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Moreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S M Schwager
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J R Cerhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T G Call
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N E Kay
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S L Slager
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T D Shanafelt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T D Shanafelt.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Solomon, B., Chaffee, K., Moreira, J. et al. Risk of non-hematologic cancer in individuals with high-count monoclonal B-cell lymphocytosis. Leukemia 30, 331–336 (2016). https://doi.org/10.1038/leu.2015.235

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2015.235

This article is cited by

Search

Advanced search

Quick links