FaCD Online Syndrome Fact Sheet

Last updated: 26 May 2009

Name: Chronic Lymphocytic Leukemia, Multiple Primary Malignancies in Patients with

Tumor features

breast cancer
glioma of the brain
Hodgkin disease (Hodgkin's lymphoma)
leukemia, acute myeloid (AML, incl. ANLL)
leukemia, chronic lymphocytic (CLL)
lung/bronchial cancer
melanoma, cutaneous
melanoma, uveal (choroidal, ciliary body, iris)/ocular
prostate cancer
renal cell cancer
skin cancer


Travis et al.[1] searched for excess primary cancers following CLL as first primary, in 9456 patients from the SEER dataset. Significant excesses were noted for cancers of the lung (Observed/Expected = 1.90), brain (1.98), and eye (intraocular melanoma) (3.97) as well as malignant melanoma (2.79) and Hodgkin's disease (7.69). Cancer risk did not vary according to initial treatment category and was constant across all time intervals after CLL diagnosis.
Mellemgaard et al.[2] performed a similar study in 7391 Danish CLL patients. Following CLL as first primary, increased risks were found for cancer of the lung and prostate in men (RR = 2.0 and 1.5 respectively), renal parenchyma in both sexes (2.8 for men, 3.6 for women) non-melanoma skin cancer in both sexes (4.7 for men, 2.4 for women) and sarcomas (3.3 for men, 2.8 for women).

In a cohort of 2,028 US patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, Tsimberidou et al[3] observed a significantly higher observed/expected ratio of Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute myeloid leukemia, other myeloid (including monocytic) leukemias, melanoma, and female breast cancers compared with the general population. An association between CLL treatment and the development of other cancers was not evident in this study.

General aspects to consider with respect to multiple primary tumors:
- Shared genetic (immune response, metabolic/hormonal/DNA-repair pathways) or non-genetic (chemical carcinogens, radiation, viruses, life-style) risk factors
- Therapy (radiation, chemotherapy, hormonal,...) related effects
- Possible bias because of increased surveillance and autopsy findings


[1] Travis LB, Curtis RE, Hankey BF, Fraumeni JF, Jr. Second cancers in patients with chronic lymphocytic leukemia. J Natl Cancer Inst 1992; 84(18):1422-1427.
[2] Mellemgaard A, Geisler CH, Storm HH. Risk of kidney cancer and other second solid malignancies in patients with chronic lymphocytic leukemia. Eur J Haematol 1994; 53(4):218-222.
[3] Tsimberidou AM, Wen S, McLaughlin P, O'Brien S, Wierda WG, Lerner S, Strom S, Freireich EJ, Medeiros LJ, Kantarjian HM, Keating MJ. Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma.J Clin Oncol. 2009 Feb 20;27(6):904-10.