Abstract
Introduction: Hematologic malignancies have caused over 1.4 million deaths among U.S. adults between 1999 and 2020, with 185,840 new cases diagnosed in 2020 alone. Although treatments like chemotherapy and radiation have improved survival rates, they also increase the risk of developing aplastic anemia due to bone marrow damage. Hematological malignancies and aplastic anemia also share common risk factors including exposure to toxins, radiation, genetics, infections and immune dysregulation. Aplastic anemia carries a poor prognosis with 30–40% five-year mortality and a median survival of under one year when untreated, mainly due to bone marrow failure leading to fatal infections and bleeding. This study uses the CDC WONDER database to analyze mortality trends in U.S. adults with coexisting hematological malignancies and aplastic anemia, with the goal of better understanding their combined burden and informing future care strategies.
Methods:
We conducted a retrospective analysis of the CDC WONDER mortality data using the publicly available death certificates from 1999 to 2023 for individuals aged ≥ 25 years. Hematological malignancies and aplastic anemia were identified using the International Classification of Disease, tenth revision (ICD-10) codes C81-C96 and D61, respectively. Death certificates were identified where hematological malignancies and aplastic anemia were listed as contributing or multiple causes of death. Age-adjusted mortality rates (AAMRs) were extracted per 100,000 of the population. Joinpoint regression was used to calculate Annual Percent Changes (APCs) in AAMRs, and trends were analyzed by gender, race, regions, urbanization and states
Results:
A total of 35,954 deaths were reported from 1999 to 2023, with hematological malignancies and aplastic anemia as contributing causes of death. The overall AAMR first decreased from 0.66 in 1999 to 0.54 in 2007 (APC: -2.08; 95% CI: -3.53 to -0.62) and then steadily rose significantly until 2023 to 0.79 (APC: 2.44; 95% CI: 1.97 to 2.92). Men demonstrated higher AAMR than women (0.94; 95% CI: 0.88 to 1.00 for men vs 0.55; 95% CI: 0.51 to 0.59 for women) throughout the study period. Non-Hispanic (NH) White individuals showed the highest AAMR (0.65), followed by NH Black (0.63), Hispanic (0.58) and NH Asians or Pacific Islanders (0.46). Non-metropolitan areas had slightly increased AAMRs than metropolitan areas (0.70 vs 0.61). Among census regions, the Midwest had the highest mortality rates (0.68), while the Northeast had the lowest AAMR (0.52). Older adults aged 65 and above had the highest mortality burden among different age groups (average AAMR: 2.3).
Conclusion:
Our retrospective analysis reveals a biphasic trend in mortality due to hematological malignancies and aplastic anemia, with an initial decrease in AAMR until 2007, likely due to advances in diagnostic strategies, chemotherapeutic regimens, hematopoietic stem cell transplantation, and supportive care. The subsequent increase in mortality may be attributed to aging population, increasing comorbidities and improved usage of death certificates. The significantly higher burden of mortality in older adults reflects the challenges in diagnosis and treatment in this age group. The demographic and geographic disparities with significantly higher mortality burden among men, NH Whites, non-metropolitan areas and the Midwest, highlight the underlying differences in healthcare access, socioeconomic factors, and availability of specialized hematology care. These findings underscore the need for targeted interventions to reduce disparities and improve outcomes in high-risk populations.
