Background: Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-hodgkin lymphoma (NHL), accounting for up to 30% of all lymphoma cases. A second primary malignancy is a significant complication in patients with hematologic cancers, with dire effects on morbidity and mortality. The data on second primary malignancies (SPM) in DLBCL is limited. We therefore aim to evaluate and discuss this risk.

Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER) database, comparing secondary cancer rates among DLBCL cases diagnosed from 2000 to 2022. A second primary malignancy was defined as a malignancy developing six or more months after an index DLBCL diagnosis. We used the SEER MP-SIR session to obtain the p-value, observed/Expected (O/E) ratio, and absolute excess risk (AER) per 10,000. The histologic code for DLBCL is 9680/3. The age cut-off used for this study was 20.

Results: 134,366 DLBCL cases from 2000-2022 met our inclusion criteria and were included in our study. Of these cases, 9,893 (7.4%) developed second primary malignancies. The mean age of SPM was 71.17 years. The risk of developing SPM was significantly higher than the general population, with an O/E ratio of 1.29 (CI 1.27-1.32, AER 42.24, p < 0.05). Most common SPMs included Esophagus (O/E ratio 1.26 CI 1.03-1.52, p < 0.05), Stomach (O/E ratio 1.50 CI 1.29-1.72, p < 0.05), Lung (O/E ratio 1.21 CI 1.15-1.28, p < 0.05), Melanoma (O/E ratio 1.18 CI 1.08-1.29, p < 0.05, Thyroid (O/E ratio 2.12 CI 1.85-2.41, p < 0.05, Acute Myeloid Leukemia (AML) (O/E ratio 6.25 CI 5.68-6.86, p < 0.05), chronic myeloid leukemia (CML) (O/E ratio 2.10 CI 1.61-2.68)

Conclusions :Compared to the general population, there is a statistically significant increased risk of secondary primary malignancies in DLBCL patients. DLBCL survivors would benefit from close site-specific screening modalities and follow-up, based on individual risk factors for the development of SPM.

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2025
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