Disparities in Leukemia Incidence and Mortality By Sex and Race in the United States from 1999 to 2020: A Retrospective Longitudinal Cross-Sectional Study Using Joinpoint Regression and Negative Binomial Analysis
Authors: Bagga Arindam , Parvataneni Tarun , Atodaria Kuldeepsinh , Biswas Navanita , Sripathi Keerthi , Varma Samyukta , Gill Harmeet , Sandhu Jujhar , Kanitkar Amaraja , Patel Urvish , Obulareddy Sri Jeevani 
Published: December 2024

Background: Leukemia ranks as the 6th leading cause of death among males and the 8th among females in the United States. It is also the 9th most common cancer in men and the 10th in women nationwide. The study analyzed leukemia incidence, mortality, and Mortality-to-Incidence Ratios (MIR) in the US from 1999-2020, examining trends across sex and race groups to identify changes over time and evaluate the impact of advancements in leukemia management across these demographics.
Methods: This retrospective longitudinal cross-sectional study extracted incidence and mortality rates per 100,000 individuals as well as age-adjusted MIR, stratified by sex and race, from the CDC WONDER database for the years 1999-2020. Joinpoint regression analysis examined Annual Percent Change (APC) and Average Annual Percent Change (AAPC) after summarizing raw data into year-wise means. Age-adjusted mortality and incidence rates by sex and race (weighted by population) were computed. Negative binomial regression analysis was utilized to analyze odds ratios (OR) for mortality and incidence rates.
Results: Between 1999 and 2020, 1,008,338 cases of leukemia (57.70% males) and 494,728 leukemia-associated deaths (57.01% males) were reported in the US. There was an initial rise in incidence from 1999 to 2016 (APC 0.66% per year), followed by a constant decline rate (APC -5.46% per year). The overall decline was 0.53% per year (AAPC 95% CI: -0.99% to -0.19%), p&lt;0.05. Males had higher age-adjusted incidence rates and ratios than females (rate: 16.87% vs. 10.39%, Odds Ratio [OR]: 1.51 [1.40-1.63]), p&lt;0.05. A declining trend was observed in the APC in age-adjusted incidence in the following subgroups: males (-11.62% since 2018), females (-5.25% since 2016), and Native Americans (-22.43% since 2018). Age-adjusted incidence rates were lower for Asians, African Americans, and Native Americans (8.11%, 10.91%, and 10.32%; OR: 0.54 [0.49-0.60], 0.67 [0.61-0.73], and 0.65 [0.59-0.73], respectively) compared to Whites (14.44%), p&lt;0.05. In terms of mortality, there was a constant significant decline of 1.75% per year (95% CI: -2.04% to -1.48% AAPC), p&lt;0.05. Males had higher age-adjusted mortality than females (mortality: 8.69% vs. 4.96%, OR: 1.68 [1.50-1.89]), p&lt;0.05. African Americans and Whites had significantly higher mortality (6.25% and 7.10%; OR: 1.37 [1.15-1.65] and 1.76 [1.48-2.10]), p&lt;0.05, while Asians had non-significantly lower mortality (3.87%, OR: 0.89 [0.72-1.09]) compared to Native Americans (4.42%). The overall Mortality-to-Incidence Ratio (MIR) declined significantly from 1999 to 2020 (AAPC: -1.52% per year, 95% CI: -1.70% to -1.30%). This trend can be divided into three periods: a decrease from 1999 to 2010 (APC -1.55% per year), a sharper decline from 2010 to 2016 (APC -3.00% per year), and a non-significant increase from 2016 to 2020 (APC 0.84% per year). Declining MIR trends were consistent across all subgroups of sex and race.
Conclusion: Leukemia mortality consistently declined from 1999 to 2020, while a decline in incidence has been observed since 2016. Further studies to evaluate the cause of the initial increase in incidence would be beneficial. The declining MIR trend was consistent across both sexes and all racial groups, likely suggesting improved outcomes in leukemia due to advancements in management and treatment strategies over the studied period.