Risk of Second Malignancies after Non Hodgkin Lymphoma: A Cohort Study of 22,466 Survivors in Israel

Previous studies have shown an increase risk of second malignancies after non-Hodgkin's lymphoma (NHL). This is probably related to genetic predisposition, molecular and pathologic background, immunological status and type of therapy given for the lymphoma.

We evaluated the risk of second solid tumor and hematological malignancy among 24,666 survivors of NHL diagnosed in Israel during 1980-2011. Data was taken from the records of the Israeli National Cancer Registry (INCR), as all public and private medical facilities, and pathology laboratories engaged in diagnosing cancer patients in Israel, are obliged to send a copy of the medical summary, demographic data and details of diagnosis, to the registry. The INCR records all the available information on these cases, including the date of diagnosis and tumor location.

The cohort of 24,666 NHL-patients included Jews (22,601 cases) and Arabs (2065 cases). Median age at diagnosis of Jews was 61.3 years, and 48.2 for Arab patients. Of all Jews with NHL: 11,265 (50%) were of European-American descent, 5005 (22%) Asian African and 6114 (27%) were born in Israel. In both Jewish and Arabs sub-groups, there were more males (52%, 56% respectively). Second cancers were reported in 2010 patients; 1918 Jews (95.5 %), and 92 Arabs (4.5 %). Evaluation of the results was restricted to the cohort of Jews only, due to the small number of Arab patients.

Second malignancies in all recorded sites were significantly more common in males with standardized incidence ratio (SIR) of 1.28, and 1.25 for females. This was even more pronounced for secondary hematological malignancies, with SIR of 1.97 and 1.81 respectively, in a total of 283 cases. (Table)

Of the secondary hematological malignancies; the most frequent were leukemias (31%) and NHL (29%), followed by multiple myeloma (14%), Hodgkin lymphoma and mycosis fungoides (both 8%).

In conclusion; there is an increased risk of second malignancies after NHL in Israel, particularly leukemia and non- Hodgkin lymphoma. These clearly occur more frequently in Jews, suggesting that ethnicity and genetic susceptibility may be important risk factors.