Risk of secondary myeloid neoplasms following treatment in patients with grade I-II follicular lymphoma: a retrospective cohort study

Background To assess the association between initial treatment modalities and the risk of developing subtypes of myeloid neoplasms (MNs) in survivors with grade I-II follicular lymphoma (FL) and to evaluate their impact on survival outcomes. Methods Patients diagnosed with grade I-II FL as their first malignancy were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression and Poisson regression were used to evaluate the treatment-associated risk (RR) for MNs and the Kaplan-Meier method was applied to assess the survival outcomes. Results Among 19,326 FL patients, 9539 patients (49.36%) received chemotherapy, and 2890 patients (14.95%) received radiotherapy as part of their initial treatment. With a median follow-up time of 103 months, 90, 82, and 23 patients developed myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), respectively. In both multivariable competing risk regression analysis and Poisson regression analysis, chemotherapy was found to be associated with a higher risk of developing MDS (adjusted hazard ratio (HR), 1.85; 95% confidence interval (CI), 1.13-3.02; adjusted RR, 1.88; 95% CI, 1.18-3.04), total AML (adjusted HR, 2.22; 95% CI, 1.33-3.71; adjusted RR, 2.24; 95% CI, 1.37-3.78), and AML with myelodysplasia-related changes (AML-MRC) (adjusted HR, 3.42; 95% CI, 1.24-9.44; adjusted RR, 3.48; 95% CI, 1.52-9.07). Additionally, radiotherapy also increased the risk of AML-MRC (adjusted HR, 2.74; 95% CI, 1.12-6.72; adjusted RR, 2.73; 95% CI, 1.10-6.08). The development of AML or MDS was associated with worse overall survival (OS) and disease-specific survival (DSS) in grade I-II FL survivors. Conclusion Initial chemotherapy and radiotherapy in patients with grade I-II FL were associated with increased risk of certain subtypes of MNs, such as MDS and AML. The importance of balancing risks and benefits should be emphasized in initial FL treatment.