Second Primary Malignancies in Long Term Acute Lymphoblastic Leukemia Survivors of Three Age Groups

Background:

Survivors of Acute Lymphoblastic Leukemia (ALL) are at an increased risk of subsequent malignancies secondary to genetic makeup, and exposure to environmental and treatment factors. Younger patients are exposed to different risk factors than older patients, which may result in differences in the risk of second malignancies. Additionally, there is not much information regarding the long term risk of subsequent malignancies. Therefore, we conducted this study to analyze and compare the risks of all second malignancies in patients aged under 15 (pediatric), 15-39 (Adolescent and Young Adult) and over 40 (Adults), five years after their initial diagnosis.

Methods:

Using data from the Surveillance, Epidemiology and End Results 9 database, Nov 2016 Sub {1973-2012}, we determined the risk of secondary malignancies in long term (five years out from diagnosis) survivors of ALL belonging to three age groups at diagnosis: less than 15, 15 to 39, and 40 and above. For the first cohort, patients younger than 15, there were 5200 patients with 69651 patient years of follow up. For the second age cohort, 15-39, there was a total of 949 patients with 10703 patient years of follow up, and for the third cohort, patients aged 40 and over, there were 365 patients with 2497 patient years of follow up. The risk of second primary malignancies is given as the standardized incidence ratio, which is calculated as such: observed incidence[O]/expected incidence[E]

Results:

Five years after an ALL diagnosis, patients under the age of 15 are at the highest relative risk of developing any type of second cancer (O/E: 3.58; CI: 2.95-4.30; N=114). Patients between the ages of 15-39 had a significantly fewer number of total cases, but still presented a high relative risk of developing any second malignancy (O/E: 1.59; CI: 1.10-2.22; N=34). Although patients over 40 had more total cases of second cancers than patients between 15-39, the data did not present any statistical significant increased relative risk for developing a second cancer when compared to matched population (O/E: 1.06; CI: 0.76-1.44 ; N=41). Patients under the age of 15 are at the highest risk of developing a second cancer of the salivary gland (O/E: 39.75; CI: 17.16-78.33; N=8). For patients under the age of 15, cancers of the oral cavity and pharynx (O/E: 15.38; CI: 7.37-28.28; N=10), brain, (O/E: 10.98; CI: 6.79-16.78; N=21) and thyroid (O/E: 7.07; CI: 4.70-10.21; N=28) represent the highest number of second cancers. Similarly, patients aged 15 to 39 are also at a high risk of developing a cancer of the salivary gland (O/E: 25.70; CI: 3.11-92.85; N=2). For patients aged 40 and above, cancer of the gum and other mouth has the highest increased risk (O/E: 14.73; CI: 1.78-53.22; N=2), but again there are relatively few patients so we cannot make any accurate estimates for second cancers. This decrease in the total number of patients may be due to an increase in the number of deaths resulting from ALL. In the database analyzed patients over 40 surviving one year, we had a total of 1,287 patients, but the same age cohort 4 more years from initial diagnosis only had 365 patients. Only 28% of patients over 40 survived after 5 years.

Conclusion:

There are several second malignancies that long term survivors of ALL are at increased risk of developing, even after 5 years from their initial diagnosis. These risks vary by age group, with young patients at substantially higher relative risk compared to their peers. However, unfortunately most adult patients died within the first five years of diagnosis. This information may help physicians effectively monitor survivors of ALL of all ages for any second cancers.

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