Burden of haematological malignancies among children, adolescents and young adults: Global and high-income region insights from the GBD 2021 study.

INTRODUCTION

Despite advances in cancer epidemiology, our understanding of the distribution and temporal trends of haematological malignancies remains largely incomplete, especially for younger age groups and in high‐income settings. 1 Recent global burden analyses have shown rising age‐standardized incidence rates (ASIRs) in many high social‐demographic index (SDI) regions for haematological cancers, alongside declines in mortality and disability‐adjusted life years (DALYs), but these studies have generally focused on all ages rather than the 0‐ to 24‐year bracket. 1 , 2 , 3 Studies on childhood and adolescent leukaemia have similarly documented large regional disparities, with high‐income countries showing higher incidence but better survival, yet many omit older adolescents and young adults. 4 , 5 Moreover, while genomic studies provide insight into age‐related biological variation in haematological malignancies, few epidemiological works combine all major haematological cancer types with stratification by 5‐year age between 0 and 24, incidence, prevalence, DALYs and deaths. 6 , 7 Therefore, a comprehensive assessment of haematological malignancy burden for the 0–24 age group, especially in high‐income regions, is needed to inform targeted prevention, resource allocation and policy.

Although recent studies have described the global and regional burden of haematological malignancies, important limitations remain. Huang et al. reported that analyses of adolescents and young adults did not disaggregate data into 5‐year age groups within the 0–24 range or consistently include DALYs, prevalence and deaths for all subtypes. 8 Zhou et al. and Chen et al. showed subtype‐specific trends in leukaemia but focused on all ages, with limited granularity for the youngest cohorts. 9 , 10 Zhuge et al. reported clear multiple myeloma trends in high‐SDI regions, but primarily among older age groups. 11 Ni et al. highlighted acute lymphoblastic and acute myeloid leukaemia, but their scope excluded other haematological cancers. 12 Trama et al. demonstrated survival differences between adolescents, young adults and children, but did not comprehensively examine incidence or prevalence trends across subtypes. 13 Pan et al. reported that, although age‐standardized death and DALY rates were stable or declining globally, absolute numbers continued to rise and young populations in high‐income regions were not analysed separately. 14 Collectively, these gaps underscore the lack of fine age‐specific, subtype‐inclusive and region‐focused analyses for haematological malignancies in children, adolescents and young adults.

Building on these observations, the present study is designed to comprehensively assess the burden of haematological malignancies among individuals aged 0–24 years, with particular emphasis on high‐income regions. By harmonizing data across the major haematological cancer categories and recalculating age‐standardized rates (ASR) in 5‐year intervals, we aim to provide consistent and comparable estimates of incidence, prevalence, DALYs and mortality. This refined approach enables more accurate delineation of age‐, sex‐ and region‐specific disparities that have not been fully characterized in prior research. Ultimately, our findings are expected to generate robust epidemiological evidence to guide precision prevention strategies, inform rational allocation of health resources and support policies that improve outcomes for children, adolescents and young adults worldwide.

MATERIALS AND METHODS

Data sources

We used data from the Global Burden of Disease Study 2021 (GBD 2021), which provides comprehensive and comparable estimates of incidence, prevalence, deaths and DALYs for 369 diseases and injuries across 204 countries and territories from 1990 to 2021. The GBD employs standardized definitions and modelling strategies to ensure internal consistency across geographies, time periods and disease categories. Non‐fatal outcomes are modelled using Disease Modeling – Meta‐Regression (DisMod‐MR), and cause‐specific mortality is estimated via Cause of Death Ensemble Model (CODEm), with spatiotemporal smoothing and uncertainty propagation through 1000 draws. Haematological malignancies were defined according to the International Classification of Diseases codes and included five subtypes: Hodgkin lymphoma, non‐Hodgkin lymphoma, multiple myeloma, leukaemia and myelodysplastic, myeloproliferative neoplasms and others.

Study population and stratification

The analysis was restricted to individuals aged 0–24 years. To capture developmental heterogeneity within this age range, we stratified the population into 5‐year age groups: 0–4, 5–9, 10–14, 15–19 and 20–24 years. Estimates were further disaggregated by sex, five SDI quintiles and by geographic regions, with a particular emphasis on five high‐income regions: Australasia, high‐income Asia Pacific, high‐income North America, Southern Latin America and Western Europe.

Measures of burden

We extracted ASIRs, prevalence rates, death rates and DALY rates per 100 000 population, along with the corresponding absolute numbers. Uncertainty intervals (95% UI) were generated using 1000 draws from the posterior distribution of each estimate. Temporal changes between 1990 and 2021 were quantified using the estimated annual percentage change (EAPC) with its 95% confidence interval. DALYs were calculated as the sum of years of life lost due to premature mortality and years lived with disability, following GBD standard methods.

Cause aggregation and standardization

To assess the overall burden of haematological malignancies, estimates for the five subtypes were harmonized and aggregated following established GBD cause hierarchy procedures. Age‐standardized rates were recalculated for the combined category using the GBD world standard population. This approach ensured comparability across time, regions and demographic groups, while accounting for overlapping case definitions and potential double counting.

Statistical analyses and visualization

EAPCs were calculated using log‐linear regression models fitted to the natural logarithm of ASIRs over time. Dual‐axis line‐and‐bar charts were used to show long‐term temporal trends, displaying ASIRs on the left axis and absolute counts on the right. Pyramid plots were constructed to depict age‐ and sex‐specific distributions of incidence, prevalence, DALYs and deaths, with different colours representing haematological subtypes. Global maps were generated to visualize geographic distributions of ASIRs and numbers for 2021. To evaluate health inequalities across countries and regions, we employed the slope index of inequality (SII) and the concentration index (CI). The SII was derived from population‐weighted linear regression of ASR (ASR per 100 000) on the ridit‐transformed SDI rank (0–1); the slope represents the absolute difference in ASR between the highest and lowest SDI, with 95% CIs. The CI was computed as twice the covariance between the health variable and the fractional SDI rank, divided by the mean, with 95% CIs. Both indices were computed separately for incidence, DALYs, prevalence and deaths in 2021. To mitigate changes in case ascertainment across income settings and over time, GBD applies source mapping, cause‐of‐death redistribution and spatiotemporal modelling with covariates reflecting diagnostic capacity, with uncertainty propagated through posterior draws. All analyses were conducted using R software (version 4.2.2) and Stata (version 17.0), and data were processed in accordance with the analytic framework of the GBD 2021.

RESULTS

Global burden and trends

From 1990 to 2021, the global burden of haematological malignancies in individuals aged 0–24 years demonstrated heterogeneous trends across incidence, prevalence, DALYs and deaths (Figure 1A,B , Figure S1A,B ). In 2021, there were an estimated 152 642 new cases worldwide, corresponding to an ASIR of 4.79 per 100 000 population (95% UI: 3.59–6.05, Table 1 ). The overall incidence exhibited a modest but significant decline, with an EAPC of −0.72 (95% CI: −0.81 to −0.64, Table 1 ). By contrast, the prevalence of haematological malignancies remained relatively stable (Figure S1A,B ). In 2021, a total of 1 021 927 individuals were living with these cancers globally, yielding an age‐standardized prevalence rate (ASPR) of 31.61 per 100 000 (95% UI: 24.18–39.85, Table S2 ). The temporal trend in prevalence showed no significant change, with an EAPC of 0.03 (95% CI: −0.07 to 0.13, Table S2 ). The disease burden measured by DALYs was substantial, with 5 173 849 DALYs in 2021, equivalent to an age‐standardized DALY rate of 160.03 per 100 000 (95% UI: 121.45–193.82, Table S1 ); unlike prevalence, DALY rates displayed a marked downward trajectory over the study period, with an EAPC of −2.12 (95% CI: −2.18 to −2.06, Figure 1B ; Table S1 ). This decline reflects improvements in survival and reductions in premature mortality, although the absolute DALY burden remained high. Global mortality also decreased steadily (Figure S1B ). In 2021, there were 65 589 deaths attributed to haematological malignancies in the 0–24 age group, corresponding to an age‐standardized death rate of 2.03 per 100 000 (95% UI: 1.55–2.45, Table S3 ). The EAPC for mortality was −2.07 (95% CI: −2.13 to −2.02), underscoring substantial progress in reducing fatal outcomes in young populations (Table S3 ).

Burden by haematological malignancy subtype

Marked heterogeneity was observed in haematological malignancies among 0‐ to 24‐year‐olds in 2021 (Figure 2A–D , Figure S2A–D ). Leukaemia dominated with 80 527 new cases (ASIR 2.55, 95% UI: 1.88–3.14), followed by non‐Hodgkin lymphoma (35 580; ASIR 1.10). Hodgkin lymphoma and myelodysplastic/myeloproliferative neoplasms contributed 14 681 and 21 653 cases, respectively, while multiple myeloma was extremely rare (201 cases). Incidence declined for most subtypes, particularly leukaemia (EAPC –0.93), whereas multiple myeloma showed a modest increase (EAPC +2.20).

In terms of burden, leukaemia accounted for 3.54 million DALYs (Age‐Standardized Death Rate [ASDR] 110.29), followed by non‐Hodgkin lymphoma (1.19 million). Multiple myeloma contributed fewer than 10 000 DALYs but showed an upward trend. Prevalence was highest in leukaemia (378 495; ASPR 12.20) and non‐Hodgkin lymphoma (276 504; ASPR 8.56), with lower but notable levels in Hodgkin lymphoma and myelodysplastic/myeloproliferative neoplasms. Mortality was greatest for leukaemia (44 798 deaths; ASDR 1.39), followed by non‐Hodgkin lymphoma (15 078) and Hodgkin lymphoma (5023). Deaths from multiple myeloma and myelodysplastic/myeloproliferative neoplasms were rare. Overall, most subtypes showed declining mortality, except multiple myeloma, which exhibited slight increases.

Age‐ and sex‐specific patterns globally and in high‐income regions

Across the global 0‐ to 24‐year population, clear age and sex gradients were observed (Figure 2A–D , Figure S2A–D ). In 2021, males showed a higher burden than females: incidence was 90 977 (ASIR 5.56, 95% UI: 3.93–7.31) vs. 61 665 (ASIR 3.97, 95% UI: 2.84–5.09) cases, and DALYs were 3.06 million (ASDR 185.24) vs. 2.11 million (ASDR 134.85) (Table 1 , Table S1 ). Prevalence reached 616 363 in males (ASPR 37.38) and 405 565 in females (ASPR 26.00) (Table S2 ), while deaths were 38 630 in males (ASDR 2.33) and 26 959 in females (ASDR 1.71) (Table S3 ). All indicators declined over time. Age patterns showed a peak in <5 years (ASIR 7.39; DALY rate 189.36; ASPR 42.33), a decline in mid‐childhood and a partial rebound in adolescence and early adulthood, with mortality lowest at 5–9 years and rising to 2.26 per 100 000 at 20–24 years. High‐income regions mirrored global trends, with male predominance, heavy burden in <5 years and mortality increasing into young adulthood (Figure 3A–D , Figure S3A–D ).

Trends in high‐income regions and geographic distribution

Marked regional disparities emerged when stratifying by SDI quintiles and high‐income regions (Figure 3A–D , Figure S3A–D ; Figure 4A–D , Figure S4A–D ). In 2021, incidence was highest in high‐SDI regions, with an ASIR of 7.17 per 100 000 (95% UI: 6.16–8.32) and 20 946 new cases (95% UI: 18 049–24 243), showing only a modest decline over time (EAPC –0.42, 95% CI: −0.55 to −0.28, Table 1 ). By contrast, low‐SDI regions had substantially lower incidence (ASIR 3.63, 95% UI: 2.39–4.96), but the rate of decline was steeper (EAPC –0.86, 95% CI: −0.92 to −0.81). High‐income regions demonstrated similar patterns (Figure 1C,D ). In Australasia, incidence in 2021 was 572 cases (95% UI: 412–780), with an ASIR of 6.02 (95% UI: 4.34–8.21). The high‐income Asia Pacific region reported 3075 new cases (95% UI: 2364–3938), with the highest ASIR at 8.68 (95% UI: 6.70–11.04). High‐income North America contributed the largest absolute numbers, with 7573 incident cases (95% UI: 6384–9009) and an ASIR of 6.73 (95% UI: 5.67–8.01). Southern Latin America recorded 1159 incident cases (95% UI: 888–1507) and ASIR 4.66 (95% UI: 3.56–6.07) (Table 1 ).

DALY rates varied similarly across regions (Table S1 ). High‐SDI regions had an age‐standardized DALY rate of 78.01 (95% UI: 70.58–85.26), while low‐SDI regions exhibited the highest rates at 201.74 (95% UI: 133.26–268.62). Within high‐income regions, the high‐income Asia Pacific recorded the highest DALY rate of 76.30 (95% UI: 66.53–87.20). Prevalence and mortality showed parallel patterns (Figure S1C,D , Figures S3A–D and S4A–D ; Tables S2 and S3 ). Conversely, low‐SDI quintiles had both the lowest prevalence (ASPR 17.86, 95% UI: 11.86–24.58) and the highest mortality (ASDR 2.51, 95% UI: 1.67–3.33). Within high‐income regions, mortality ranged from 0.80 per 100 000 in Australasia (95% UI: 0.67–0.96) to 0.94 in Asia Pacific (95% UI: 0.83–1.06) and 0.87 in North America (95% UI: 0.82–0.93).

Taken together, these findings reveal that, while high‐income regions carry a disproportionate share of incidence and DALYs in young populations, survival outcomes are more favourable, leading to lower death rates. Conversely, low‐income settings face fewer cases but poorer survival, underscoring inequities that are visible in global maps of burden distribution (Figure 4 , Figure S4 ).

Inequalities across regions and development levels

Substantial health inequalities were evident when stratifying haematological malignancy burden by socioeconomic development (Figure 5A–D , Figure S5A–D ; Tables S4–S6 ). In 2021, the SII for incidence was 4.12 per 100 000 (95% CI: 3.56–4.68), indicating markedly higher rates in the most developed regions (Table S4 ). Concentration indices (CI) confirmed this pattern, with values of 0.27 for incidence and 0.24 for DALYs (Table S6 ), signifying concentration of disease burden in high‐SDI settings. In contrast, mortality and DALYs remained disproportionately elevated in low‐SDI regions, with negative SII values for deaths (–0.86 per 100 000, 95% CI: –1.03 to –0.69, Table S5 ). Together, these metrics reveal a dual burden: high‐income regions carry more cases due to better diagnosis and survival, while poorer regions face disproportionately higher fatality and DALY impact.

DISCUSSION

The present study provides a comprehensive assessment of haematological malignancies among children, adolescents and young adults aged 0–24 years, addressing an important gap in previous literature that has largely focused on adults or single cancer subtypes. We found that, from 1990 to 2021, the global incidence and prevalence of haematological malignancies in this age group remained relatively stable, while DALY and mortality rates declined substantially, reflecting improvements in treatment and survival outcomes. Notably, high‐income regions carried a disproportionately high incidence and DALY burden but exhibited markedly lower mortality, underscoring the impact of advanced diagnostic capacity and healthcare resources.

One of the most striking findings of this study is the stability of global incidence and prevalence of haematological malignancies over the 0‐ to 24‐year age span, alongside a substantial decrease in mortality and DALYs, especially in high‐income settings. This aligns with recent GBD analyses such as Pan et al., which reported rising absolute numbers but declining age‐standardized death rates globally from 1990 to 2021. 14 Among subtypes, leukaemia remains the principal contributor to incidence, deaths and DALYs globally, with a strong downward trend in both incidence and mortality. Non‐Hodgkin lymphoma and Hodgkin lymphoma also showed declines in mortality, though their incidence trends were more heterogeneous. 15 , 16 , 17 Notably, multiple myeloma exhibited a modest rising incidence despite low absolute numbers, suggesting emerging challenges. 18 , 19 , 20 These subtype differences reflect variations in risk exposure, diagnostic access and treatment advances. 2 , 21 Together, these findings highlight the importance of subtype‐specific strategies—improving leukaemia outcomes globally remains critical, while emerging increases in rare subtypes like myeloma warrant monitoring and tailored interventions.

Our analysis reveals pronounced age and sex differences in the burden of haematological malignancies among 0‐ to 24‐year‐olds. Males consistently exhibited higher incidence, DALYs, prevalence and mortality compared to females, mirroring findings by Zhang et al., who reported global male predominance in both incidence and death for haematological cancers. 2 Similarly, Trama et al. found that male survival lagged behind female in several haematological subtypes. 13 Age‐specific trends in our data show highest rates in the <5 years group, a mid‐childhood dip and partial rebound in late adolescence and early adulthood; such ‘early peak’ patterns are consistent with literature on acute lymphoblastic leukaemia and lymphoid malignancies described by Huang et al. and also in studies of paediatric acute myeloid leukemia reported by Egan et al. 8 , 22 A review of rare haematological malignancies in children and young adults by Brown and Batra also noted roughly equal male‐to‐female ratios in some rare subtypes, but with higher absolute burdens in males due to incidence differences. 23 These differences likely reflect a combination of biological, diagnostic and environmental risk factors, underscoring the need to tailor prevention and therapeutic strategies by age and sex.

Our findings underscore striking regional and socioeconomic disparities in the burden of haematological malignancies among children, adolescents and young adults. High‐SDI and high‐income regions consistently demonstrated the highest incidence and DALY rates, yet with markedly lower mortality, reflecting advanced diagnostic capacity, comprehensive supportive care and the availability of curative therapies. Conversely, low‐SDI settings reported fewer absolute cases but disproportionately higher death rates and DALY burdens, highlighting delayed diagnosis, restricted access to essential medicines and gaps in treatment continuity. This duality mirrors broader global evidence. Recent GBD and Global Cancer Observatory (GLOBOCAN) analyses have documented rising absolute case numbers coupled with declining age‐standardized mortality rates, most prominently in high‐income countries where survival has improved substantially. 2 , 7 , 24 By contrast, low‐ and middle‐income countries continue to face treatment‐related mortality exceeding 30%–40%, often due to resource limitations, therapy abandonment and limited infrastructure. 25 , 26 , 27 , 28 In paediatric and adolescent leukaemia, for example, declines in mortality and DALY rates are concentrated in high and high‐middle SDI regions, while improvements remain modest in the lowest strata. 29 , 30 , 31

Geospatial mapping of burden further reveals clustering of high incidence and prevalence in affluent regions, but the persistence of high fatality ratios in under‐resourced areas. This echoes recent cancer surveillance reports, which emphasize that, while therapeutic innovation has reshaped outcomes in developed countries, inequities remain entrenched globally. 32 , 33 Current initiatives, including the WHO Global Initiative for Childhood Cancer, aim to close these gaps by scaling early diagnosis, improving access to standardized protocols and ensuring the availability of essential medicines. 34 , 35 , 36 , 37 Taken together, our results reinforce a ‘dual burden’ paradigm: high‐income regions bear greater diagnostic and treatment demands but achieve better survival, whereas low‐SDI countries suffer fewer cases but higher lethality and disability. Bridging this divide requires targeted policies that not only sustain survival gains in wealthy regions but also prioritize investment in early diagnosis, supportive infrastructure and equitable treatment access in resource‐limited settings.

This study has several limitations. First, all estimates were derived from GBD modelling, and data quality varies across countries. Second, we could not capture molecular subtypes or treatment heterogeneity within each malignancy. Third, socioeconomic, environmental and genetic determinants were not directly analysed. Future studies integrating real‐world data and prospective cohorts are needed to validate and extend our findings.

CONCLUSIONS

In summary, this study provides the first comprehensive evaluation of haematological malignancies in children, adolescents and young adults across 204 countries from 1990 to 2021. We found stable incidence and prevalence but significant global declines in DALYs and mortality, with leukaemia remaining the dominant contributor. High‐income regions carried greater incidence yet achieved better survival, while low‐SDI regions experienced disproportionate fatality, reflecting persistent inequities. These findings highlight the urgent need for subtype‐specific strategies, strengthened early diagnosis and equitable treatment access to reduce preventable deaths and disability worldwide.

AUTHOR CONTRIBUTIONS

Shujuan Xu was responsible for the conception, design, material preparation, data collection, data analyses and preparation of the first draft of the study. Baihua Yang was responsible for the conception, design, material preparation, data collection, data analyses and preparation of the first draft of the study. Xinxin Liu was responsible for the material preparation, data collection, data analyses and preparation of the first draft of the study. Zhenshu Xu was responsible for data analyses and preparation of the first draft of the study. Ping Weng was responsible for the conception, design, preparation of the first draft and review of the final manuscript of the study.

FUNDING INFORMATION

This study was funded by Startup Fund for Scientific Research, Fujian Medical University (Grant number: 2020QH1103); National Key Clinical Specialty Discipline Construction Program (2021‐76); Fujian Provincial Clinical Research Center for Hematological Malignancies (2020Y2006).

CONFLICT OF INTEREST STATEMENT

There are no conflicts of interest to declare.

ETHICS APPROVAL STATEMENT

The Institutional Review Board of the University of Washington examined and authorized a consent waiver for the GBD research. In‐depth details regarding the ethical guidelines are available on the official portal at http://www.healthdata.org/gbd/2021 .

Supporting information

Figure S1.

Figure S2.

Figure S3.

Figure S4.

Figure S5.

Table S1.

Table S2.

Table S3.

Table S4.

Table S5.

Table S6.

ACKNOWLEDGEMENTS

We sincerely appreciate the GBD work team. S.X., B.Y. and P.W. were instrumental in the conception and design of the study. S.X., B.Y. and X.L. were primarily responsible for material preparation and data collection. S.X., B.Y., X.L. and Z.X. conducted the data analyses. S.X., B.Y., X.L., Z.X. and P.W. were involved in preparing the first draft of the manuscript, and all authors provided feedback and input on subsequent versions of the manuscript. All authors have read and approved the final version of the manuscript.

DATA AVAILABILITY STATEMENT

All datasets used in this study are publicly available and can be accessed at https://vizhub.healthdata.org/gbd‐results/ .

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