Introduction:

Adolescents and young adults (AYA), defined as individuals aged 15-39 years, represent a unique population within oncology, facing distinct biological, psychosocial, and healthcare challenges. This study aims to examine the epidemiological trends, incidence and mortality rates, and identify key risk factors associated with AYA hematologic malignancies in the United States of America (USA).

Methods:

The study analyzed data from 1990 to 2021, obtained from the Global Health Data Exchange 2021 database, which is a comprehensive catalog of global health and demographic data, providing access to a wide range of datasets around the world. This study described the age-standardized rates (ASR) (per 100,000 patient-years) of incidence (ASIR), death (ASDR), and attributable risk factors of AYA hematologic malignancies (leukemia, multiple myeloma, Hodgkin and non-Hodgkin's lymphoma) in the USA. However, the strength of the association has not been validated. We computed a two-sample t-test to get the differences between the ASR of 1990 and 2021. All the statistical analysis was automated using R (version 4.4.1). We used the ARIMA model on the training set up till year 2021, and that model is used for prediction till 2040.

Results:

In 2021, among AYA in the United States, there were an estimated 2,267 cases of leukemia with 1,086 deaths, 4,410 cases of non-Hodgkin lymphoma with 521 deaths, and 2,338 cases of Hodgkin lymphoma with 141 deaths. Multiple myeloma was less frequent, with 90 cases and 60 associated deaths.

In 2021, the ASIR was highest for non-Hodgkin lymphoma (3.96), followed by Hodgkin lymphoma (2.10), leukemia (2.04), and multiple myeloma (0.08). Correspondingly, the ASDR was highest for leukemia (0.98), followed by non-Hodgkin lymphoma (0.47), Hodgkin lymphoma (0.13), and multiple myeloma (0.05). From 1990 to 2021, the annual percent change (APC) for all AYA hematological cancers showed a decreasing trend, except for ASIR and ASDR for AYA Burkitt's lymphoma (APC of ASIR: 0.74, ASDR: 0.21).

By the States of the US: In 2021, the highest ASIR and ASDR for overall leukemia were seen in West Virginia (ASIR: 2.72, ASDR: 1.54). From 1990 to 2021, overall AYA leukemia showed a declining trend in both ASIR and ASDR. AYA Hodgkin's lymphoma showed a declining trend in the USA. The most pronounced decreases in ASIR and ASDR were observed in the District of Columbia (D.C.) (APC of ASIR: - 0.71; ASDR: - 0.91) and New York (APC of ASIR: - 0.70; ASDR: - 0.88). Non-Hodgkin lymphoma showed a slight increase in ASIR in Vermont, North Dakota, and Iowa, while all other states demonstrated a decline in both ASIR and ASDR. In contrast, Burkitt lymphoma exhibited an overall increase in ASIR and ASDR, except for a decline in ASDR observed in D.C. and Rhode Island (APC: - 0.07 and - 0.02, respectively). The APC of ASIR for AYA with multiple myeloma showed a mixed pattern from 1990 to 2021. While the ASDR for MM generally declined nationwide, several states, including North Dakota, West Virginia, Maine, New Mexico, and Kentucky, experienced an increase in ASDR.

Risk factor-wise, High BMI was associated with deaths of all the hematological malignancies, with the highest deaths in MM (11.45%), followed by overall leukemia (10.93%) and non-Hodgkin (7.08%) in 2021. Occupational carcinogens and smoking are linked to Leukemia deaths. From 1990-2021, deaths attributed to high BMI increased for multiple myeloma (40.74%), non-Hodgkin lymphoma (37.13%), and leukemia (31.88%). In contrast, deaths from leukemia attributable to occupational carcinogens increased by 8.23%, while those linked to smoking declined by 44.74%.

Our analysis projects a continued decline in incidence and death rates for overall leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma through 2040. In contrast, the rates for multiple myeloma are expected to remain relatively stable over the same period.

Conclusions:

From 1990 to 2021, ASIR and ASDR declined for most AYA hematological malignancies in the United States, with the notable exception of Burkitt lymphoma, which showed consistent increases. High BMI, smoking, and occupational exposures were key modifiable risk factors, with BMI-related hematologic malignancy deaths rising across all malignancies and smoking-related leukemia deaths declining by 44.7%. These findings underscore regional disparities and highlight the growing impact of preventable lifestyle factors on AYA hematologic cancer mortality.

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2025
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