Burden and site-specific spectrum of second primary malignancies after adult acute myeloid leukemia: A population-based SEER standardized incidence ratio study with latency-stratified risk profiling (2000–2022).

Abstract

11070 Background: As survival after acute myeloid leukemia (AML) improves, second primary malignancies (SPMs) represent an increasingly relevant survivorship outcome. We quantified overall and site-specific SPM risk following adult AML and characterized latency-dependent patterns and demographic heterogeneity. Methods: We performed a population-based cohort analysis using SEER 17 registries (2000–2022). Adults (≥18 years) with AML were followed for incident SPMs occurring ≥2 months after AML diagnosis. Risk was summarized using standardized incidence ratios (SIRs; observed/expected) with 95% confidence intervals (CIs), overall and by cancer site, and stratified by latency (2–11, 12–59, 60–119, ≥120 months), age, sex, and race. Results: Overall, 751 SPMs were observed versus 563.87 expected (SIR 1.33; 95% CI 1.24–1.43). Solid tumors overall were not significantly increased (SIR 1.03; 0.94–1.12), but select sites showed excess risk: oral cavity/pharynx (SIR 2.35; 1.64–3.27), skin excluding basal/squamous (SIR 1.42; 1.04–1.90), kidney (SIR 1.88; 1.31–2.60), and eye/orbit (SIR 4.32; 1.18–11.06), while breast cancer was reduced (SIR 0.65; 0.47–0.86). Hematologic SPMs were markedly elevated (lymphatic/hematopoietic SIR 2.48; 2.06–2.96), including leukemia overall (SIR 4.42; 3.45–5.59) and acute lymphoblastic leukemia (SIR 21.51; 11.76–36.08). All-site risk remained elevated across latency windows (SIR range 1.30–1.38), while solid-tumor risk increased after 5 years (SIR 1.27 at 60–119 months and ≥120 months). Risk was highest in ages 0–59 (SIR 1.91), and remained elevated in males (1.37) and females (1.27). Conclusions: Adult AML survivors experience a sustained excess risk of SPMs, driven primarily by secondary hematologic malignancies with additional site-specific solid-tumor excesses emerging in longer-term follow-up, supporting risk-adapted survivorship surveillance. Site-specific risk of second primary malignancies after adult AML (SEER 17, 2000–2022). Site Observed Expected O/E CI Lower CI Upper All Sites 751 563.87 1.33# 1.24 1.43 All Solid Tumors 506 491.44 1.03 0.94 1.12 All Lymphatic and Hematopoietic Diseases 123 49.66 2.48# 2.06 2.96 Lymphoma 42 24.97 1.68# 1.21 2.27 Leukemia 70 15.83 4.42# 3.45 5.59 Acute Lymphocytic Leukemia 14 0.65 21.51# 11.76 36.08 Acute Myeloid Leukemia 13 4.71 2.76# 1.47 4.72 Chronic Myeloid Leukemia 22 2.11 10.40# 6.52 15.75