Survivors of chronic lymphocytic leukemia/small lymphocytic lymphoma are twice as likely to develop melanoma as are survivors of other types of non-Hodgkin lymphoma, according to a report published online Aug. 3 in Journal of Clinical Oncology.
Since patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have profound and prolonged immune dysfunction characterized by B-cell and T-cell defects, this finding suggests that immune perturbation may account for the excess of melanoma diagnoses observed in patients with non-Hodgkin lymphoma (NHL), said Dr. Clara J. K. Lam of the radiation epidemiology branch, National Cancer Institute, Bethesda Md., and her associates.
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Although patients with NHL are known to be at increased risk for melanoma compared with the general population, the reasons remain unclear. Additional factors such as chemotherapy regimens and sunlight exposure likely complicate the picture, and no studies to date have been able to account for these confounders. To assess a large enough study sample to examine these issues, Dr. Lam and her associates analyzed data concerning 44,870 NHL survivors in the Surveillance, Epidemiology, and End Results (SEER) database. They focused on older patients aged 66-83 years at NHL diagnosis (mean age, 74 years) who were followed for at least 1 year (mean follow-up, 5.5 years), of whom 13,950 had CLL/SLL.
A total of 202 melanomas developed, and the median interval between NHL diagnosis and melanoma diagnosis was 3 years (range, 1-15 years). Nearly half of these melanomas occurred in patients with CLL/SLL rather than other types of NHL; 41% occurred on the face, head, or neck, and 43% were 1 mm or more in thickness. In contrast, among survivors of other NHL types, melanoma occurred most often on the trunk, and only 28% were 1 mm or more in thickness. This aligns with previous reports that melanomas arising after NHL tend to be more advanced and aggressive than those in the general population, the investigators said (J Clin Oncol. 2015 Aug 3. doi:10.1200/JCO.2014.60.2094).
Further analysis revealed that among patients with CLL/SLL, melanoma risk was significantly increased in those who received fludarabine rather than other treatments (HR, 1.90, 95% CI, 1.08 to 3.37)), with or without the addition of rituximab. In contrast, melanoma risks were unrelated to treatment among patients who had other types of NHL.
Similarly, patients with CLL/SLL who had T-cell-activating autoimmune disorders (such as Graves’ disease, localized scleroderma, psoriasis, chronic rheumatic heart disease, asthma, or skin-related conditions) either before or after diagnosis of their leukemia/lymphoma also had 2-4 times the risk of developing melanoma than that of patients without such autoimmune disorders. In contrast, melanoma risks were unrelated to autoimmune disorders in patients with other types of NHL. This finding underscores the importance of T-cell dysfunction as a contributor to melanoma risk after CLL/SLL, Dr. Lam and her associates said.
Taken together, their findings identify which survivors of NHL are at highest risk for developing melanoma and would benefit the most from undergoing regular full-skin examinations to facilitate early detection.
This study was limited in that it was confined to patients over age 65 with NHL. The results may not be generalizable to younger patients, Dr. Lam and her associates added.