Epidemiological Trends in Incidence, Death and Associated Risk Factors of Leukemia 1990-2021 and Projection to 2040

Introduction:

Leukemia constitutes about 3.1% of all newly diagnosed cancer cases and 3.9% of deaths due to cancer in 2024 in the US. We aim to investigate the epidemiological trends (incidence and death rates) and the risk factors of Leukemia at global and regional level.

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 (per 100,000 patient-years) of incidence (ASIR), death (ASDR) and attributable risk factors of leukemia: overall, Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML), and Chronic Lymphocytic Leukemia (CLL). Regions were stratified by Sociodemographic Index (SDI) ranged from 0 (minimal development) to 1 (maximal development) and was classified as high (>0.715), high-middle (0.625 to .0715), middle (0.558 to 0.624), low-middle (0.378 to .0557), and low (<0.378) SDI regions. Geographic locations were defined based on World Bank (WB) regions (South Asia, East Asia & Pacific, Europe & Central Asia, North America, Latin America & Caribbean, Middle East & North Africa, Sub-Saharan Africa). We used autoregressive model on the training set up till year 2021 and that model is used for prediction till 2040.

Results:

In 2021, global number of cases and deaths for leukemia were 263,712 and 181,582 for males and 197,710 and 138,701 for females. The ASIR for leukemia was 6.84 for males and 4.60 for females, while the ASDR was 4.79 for males and 3.17 for females. ASIR and ASDR for both sexes decreased from 1990 to 2021 (Annual Percentage Change (APC) of ASIR: M: -0.15, F: -0.22, APC of ASDR: M: -0.27, F: -0.34). From 1990 to 2021, ASIR and ASDR decreased in ALL, AML, CML and CLL, except for ASIR of AML in males, which increased (APC: 0.01)

Smoking, high BMI and occupational exposure (OE) to formaldehyde and benzene were identified in the dataset as the risk factor for deaths in leukemia. In, 2021, globally, smoking was the highest contributor of Age-Standardized deaths (ASD) for males (16.03% vs. 3.71% in F), and high BMI for females (8.56% vs. 8.03% in M). OE contributed to < 1% of ASD.

From 1990 to 2021, for leukemia, ASD attributed to high BMI (APC: M: 37.08%, F: 40.35%) and OE (APC: M: 23.96%, F: 48.74) increased. Conversely, smoking-related ASD decreased (APC: M: -12.65%, F: -23.97%). ASD due to high BMI and OE increased for all types of leukemia, with the highest rises in ALL: high BMI-related ASD (APC: M: 66.87%, F: 79.46%) and OE-related ASD (APC: M: 45.89%, F: 80.23%). Smoking-related ASD decreased across all leukemia types, except for ALL in males (APC: 10.51%). The highest smoking-related ASD decrease was in CML (APC: M: -29.3%, F: -47.93%).

Divided by SDI Regions: In 2021, high SDI had the highest ASIR (M: 10.4, F: 6.5) and ASDR (M: 5.6, F: 3.2). From 1990 to 2021, smoking related ASD decreased in most SDI regions, except for males of middle SDI and both sexes for high-middle SDI regions. The highest decrease was in males of Low SDI (APC: -20.63%) and females of Low-middle SDI (APC: -29.83%). High BMI and OE related ASD increased in all SDI regions. From 1990 to 2021, for ALL, ASD related to some of the risk factor nearly doubled in several regions: Middle SDI (105.25%, M, high BMI), High-middle SDI (106.3%, F, high BMI), Middle SDI (115.96%, F, high BMI), and High-middle SDI (122.73%, F, OE).

Divided by WB Region: In 2021, North America had one of the highest ASIR and ASDR. From 1990 to 2021, ASIR and ASDR showed a decreasing trend, except for males in the Middle East and North Africa (APC: 0.06) and East Asia and the Pacific (APC: 0.02). From 1990 to 2021, ASD related to smoking decreased in most regions, while ASD related to high BMI increased in all regions.

Our analysis predicts an increasing incidence rate for males and a decreasing rate for females until 2040, with death rates for both sexes projected to decline till 2040.

Conclusion:

From 1990 to 2021, ASDR and ASIR decreased in ALL, AML, CML, and CLL, except for the ASIR of AML in males. Smoking, high BMI and OE were identified as important risk factors associated with leukemia-related death. From 1990 to 2021, deaths related to smoking decreased in most regions, while high BMI-related deaths increased in all regions. These findings highlight gender and regional disparity in the incidence and mortality of leukemia.