Global burden of hematologic malignancies and evolution patterns over the past 30 years – Blood Cancer Journal

Global burden of hematologic malignancies

Globally, the incident cases, deaths, and their change trends with hematologic malignancies from 1990 and 2019 are presented in Table 1. In 2019, the incident cases of leukemia, MM, NHL, and HL increased to 643.58 thousand, 155.69 thousand, 457.08 thousand, and 87.51 thousand, respectively, while the number of deaths increased to 334.59 thousand, 113.47 thousand, 254.61 thousand, and 27.55 thousand, respectively (Fig. 1A, B). Although the number was almost two to three times when since 1990, the ASDR for all hematologic malignancies is on a declining trend, while the ASIR is relatively stable. According to 2019 data, the hematologic malignancies with the highest incidence and mortality rate is leukemia (Fig. 1C, D). The global incidence trends of four major hematologic malignancies were essentially different during 1990–2019. The ASIR of leukemia and HL were 8.22 and 1.1 per 100,000 population in 2019, respectively, and the EAPC exhibited a decreasing tendency (−0.68 and −0.47). The ASIR of MM and NHL was 1.92 and 5.73 per 100,000 population in 2019, respectively, and the EAPC illustrated an increasing trend (0.25 and 0.56). However, the ASDR of leukemia, MM, NHL, and HL were 4.26, 1.42, 3.19, and 0.34 per 100,000 population in 2019, respectively, with a significant downward trend in EAPC (−1.15, −0.07, −0.09 and −2.08).

Moreover, we analyzed global trends in the proportion of new cases and deaths associated with all hematologic malignancies. Leukemia has always accounted for the largest proportion of new cases, but from 1990 to 2019 the proportion has been declining (47.9% in 2019), and leukemia has been less than half of the hematological malignancies since 2012. Compared to that, the proportion of new cases of MM and lymphoma increased (Fig. 1E). In terms of deaths, the trend in the proportion is similar to that of new cases (45.8% in 2019), but since 2007 leukemia has accounted for less than half of the deaths of hematological malignancies (Fig. 1F). For specific leukemia subtypes, the incident cases of AML, ALL, CML, and CLL increased to 124.33 thousand, 153.32 thousand, 65.8 thousand, and 103.47 thousand in 2019, respectively, while the proportion of other subtypes of leukemia decreased significantly due to the precision of classification in the past three decades (Fig. S1A, B). The number of deaths from AML, ALL, and CLL increased except for CML (Fig. S1C, D). From 1990 to 2019, CML was the type of leukemia with a decreased AISR (EAPC = −1.04) (Fig. S1E), while AML was the type of leukemia with an increased ADSR (EAPC = 0.35) (Fig. S1F).

Global burden of hematologic malignancies by gender and age

The age distribution of the population can provide evidence for primary prevention by reflecting the health burden of different age groups. People over the age of 70 are at high risk of developing hematologic malignancies, about 80% of all age groups (Fig. 2A, B). Among all age groups, the highest incidence rates of leukemia, MM, NHL, and HL were 95 plus group, 85 to 89 group, 95 plus group, and 90 to 94 group, respectively, with rates of 116.18, 23.55, 103.62, and 10.29 per 100,000 population in 2019 (Fig. 2A). The highest death rates of leukemia, MM, NHL, and HL were 95 plus group, 90 to 94 group, 95 plus group, and 85 to 89 group, respectively, with rates of 75.81, 24.71, 62.18, and 1.96 per 100,000 population in 2019 (Fig. 2B). In terms of gender, the incidence and death of hematologic malignancies are generally higher in males than in females globally (Fig. S2). The male-to-female ratio for leukemia, MM, and NHL continued to increase from 1990 to 2019 (Fig. 2C, D). The increasing male-to-female ratio may be caused by hormonal, genetic, and environmental factors and requires further research. We show the contribution of different age groups and different genders to hematologic malignancies in 1990 and 2019, not all age groups are more male than female. In most age groups of 1 to 4 and above 75, the proportion of females is larger than males (Fig. 2E, F).

A Global hematological malignancies incidence rates by age for both sexes combined in 1990 and 2019. B Global hematological malignancies deaths by age for both sexes combined in 1990 and 2019. For each group, the below column shows case data in 1990 and the above column shows data in 2019. C The sex ratio of hematological malignancies incident cases from 1990 to 2019 by four causes. D The sex ratio of hematological malignancies deaths from 1990 to 2019 by four causes. E The ratio of male to female in global hematological malignancies incident cases by age in 1990 and 2019. F The ratio of male to female in global hematological malignancies deaths by age in 1990 and 2019.

For specific leukemia subtypes, the highest incidence rates of AML, ALL, CML, and CLL in 2019 were 95 plus group, 70 to 74 group, 90 to 94 group, and 95 plus group, respectively, with rates of 56.31, 4.80, 14.69, and 25.76 per 100,000 population (Fig. S3A). The highest death rates of AML, ALL, CML, and CLL were 90 to 94 group, 85 to 89 group, 95 plus group, and 95 plus group, respectively, with rates of 13.24, 2.03, 5.19, and 24.61 per 100,000 population in 2019 (Fig. S3B). Regarding gender, all subtypes of leukemia were male with higher morbidity and mortality (Fig. S3C, D), but there were slight differences between different age groups (Fig. S4).

Leukemia burden in different regions and countries

With regard to the SDI regions, incident cases of leukemia increased across the five SDI regions. However, the ASIR decreased in the low, low-middle, middle, and high-middle SDI regions from 1990 to 2019. The highest ASIR was in the high SDI regions and was on the rise, with an EAPC of 0.05 (Fig. S5A and Table S3). Of the leukemia subtypes, AML, ALL, CML, and CLL have the highest ASIR in the high SDI regions (Fig. S5B–F). For geographical regions, the highest ASIR of leukemia in 2019 appeared in Western Europe (16.87 per 100,000 population), North America (10.69 per 100,000 population), and Australasia (10.46 per 100,000 population). The regions with the lowest ASIR were South Asia (3.81 per 100,000 population), Central Sub-Saharan Africa (3.89 per 100,000 population), and Western Sub-Saharan Africa (3.9 per 100,000 population) (Fig. 3A and Table S3). The regions with the largest increases in the ASIR were Central Europe (EAPC = 0.79), Western Europe (EAPC = 0.71), and Asia Pacific (EAPC = 0.5). In contrast, the regions with the largest declines were Central Asia (EAPC = −1.53), Eastern Sub-Saharan Africa (EAPC = −1.11), and Central Sub-Saharan Africa (EAPC = −1.09) (Fig. 3C and Table S3). Among the 204 countries, Qatar, United Arab Emirates, and Cyprus had the most dramatic increases in leukemia incident cases (percent change: 300% to 500%), while the Republic of Moldova, Georgia, and the Democratic People’s Republic of Korea had the most significant declines (percent change: −60% to −40%) (Fig. S7A and Table S7). Extremely high levels of ASIR were observed in San Marino, far higher than in any other country (35.14 per 100,000 population) (Fig. 4A). On the other hand, the lowest ASIR was found in Palau, with 2.97 per 100,000 population in 2019 (Table S7). In addition, the Cyprus (EAPC = 3.01) and Republic of Moldova (EAPC = −2.37) have the most significant increasing and decreasing trends respectively in the ASIR of leukemia (Fig. 4B).

A The ASIR of leukemia at a regional level in 1990 and 2019. B The ASDR of leukemia at a regional level in 1990 and 2019. C The EAPC in ASIR of leukemia from 1990 to 2019, by subtypes and by regions, for both sexes, combined. D The EAPC in ASDR of leukemia from 1990 to 2019, by subtypes and by regions, for both sexes, combined. Blue indicates a downward trend and Red indicates an upward trend. AML acute myeloid leukemia, ALL acute lymphoid leukemia, CML chronic myeloid leukemia, CLL chronic lymphoid leukemia, ASIR age-standardized incidence rate, ASDR age-standardized death rate, EAPC estimated annual percentage change.

A The ASIR of leukemia in 2019. B The EAPC in ASIR of leukemia from 1990 to 2019. C The ASDR of leukemia in 2019. D The EAPC in ASDR of leukemia from 1990 to 2019. ASIR age-standardized incidence rate, ASDR age-standardized death rate, EAPC estimated annual percentage change.

Notably, the leukemia of ASDR showed a significant decline over three decades in all five SDI regions, most notably in the high-middle SDI regions, with an EAPC of −1.42 (Fig. S6A and Table S3). Of the leukemia subtypes, the ASDR of AML and CLL was the highest in the high SDI regions, the ASDR of CML was the highest in the low SDI regions, and the ASDR of ALL changed from the highest in high-middle SDI to middle SDI from 1990 to 2019 (Fig. S6B–F). For geographical regions, the highest ASDR of leukemia in 2019 was observed in North America (5.65 per 100,000 population), North Africa and the Middle East (5.41 per 100,000 population), and Andean Latin America (5.15 per 100,000 population). The regions with the lowest ASDR were South Asia (2.98 per 100,000 population), Central Sub-Saharan Africa (2.99 per 100,000 population), and Asia Pacific (3.02 per 100,000 population) (Fig. 3B and Table S3). Almost all regions showed a downward trend in ASDR, with the largest declines in East Asia (EAPC = −1.99), Eastern Europe (EAPC = −1.55), and the Asia Pacific (EAPC = −1.48) (Fig. 3D and Table S3). Among the 204 countries, the United Arab Emirates and Qatar had the most pronounced increases in leukemia deaths (percent change: 350% to 500%), while the Republic of Moldova, Ukraine, and Georgia had the most significant declines (percent change: −50% to −30%) (Fig. S7B and Table S7). The two countries with higher ASDR were found to be the Syrian Arab Republic and Afghanistan, with rates of 10 to 20 per 100,000 population in 2019 (Fig. 4C). Lesotho (EAPC = 2.01) and Ukraine (EAPC = −2.48) have the most significant increasing and decreasing trends respectively in the ASDR of leukemia (Fig. 4D).

For the correlation analysis of EAPC influencing factors in leukemia, we found that EAPC (in ASIR) was not correlated with ASIR (in 1990) and SDI (in 2019), but EAPC (in ASDR) was significantly negatively connected with ASDR in 1990 (P < 0.001, ρ = −0.457). It is also significantly negatively correlated with SDI (in 2019) (P < 0.001, ρ = −0.368). Interestingly, ASIR demonstrated a clear positive correlation with SDI levels (P < 0.001, ρ = 0.781) (Fig. S8). Although the data show a trend towards a higher incidence of leukemia and lower mortality in regions with higher economic levels, it is also possible that this is due to improved reporting or earlier diagnosis.

Multiple myeloma burden in different regions and countries

During the period from 1990 to 2019, the number of MM cases increased across the five SDI regions. As for ASIR, ASIR in high SDI regions remained the highest, while that in low-middle SDI and low SDI regions were consistently low (Figs. 5A and S9A). The ASIR of MM increased across all SDI regions with the largest increase in middle SDI regions (EAPC = 0.83), while the ASIR was a slow increase in high SDI regions (EAPC = 0.33) (Fig. 5B and Table S4). For geographical regions, the highest ASIR of MM in 2019 was observed in Australasia (5.33 per 100,000 population), North America (4.8 per 100,000 population), and Western Europe (4.24 per 100,000 population). The regions with the lowest ASIR were Central Asia (0.8 per 100,000 population), Southeast Asia (0.82 per 100,000 population), and Western Sub-Saharan Africa (0.91 per 100,000 population) (Fig. 5A and Table S4). The regions with the largest increases in the ASIR were Eastern Europe (EAPC = 1.4), Tropical Latin America (EAPC = 1.3), and Central Latin America (EAPC = 1.17). In contrast, the region with the largest decline was Oceania (EAPC = −0.08) (Fig. 5B and Table S4). Among the 204 countries, Qatar and the United Arab Emirates had the most significant increases in MM incident cases (percent change: 800% to 1000%), while Tokelau and Niue had the most significant declines (percent change: −1% to −10%) (Fig. S10A and Table S7). Extremely high levels of ASIR were observed in Monaco, far higher than in other countries (14.95 per 100,000 population) (Fig. 6A). On the other hand, the lowest ASIR was found in Kyrgyzstan, with 0.62 per 100,000 population in 2019 (Table S7). In addition, Jamaica (EAPC = 4.15) and Northern Mariana Islands (EAPC = −1.29) have the most significant increasing and decreasing trends respectively in the ASIR of MM (Fig. 6B).

A The ASIR of multiple myeloma at a regional level in 1990 and 2019. B The EAPC in ASIR of multiple myeloma from 1990 to 2019 by region, for both sexes, combined. C The ASDR of multiple myeloma at a regional level in 1990 and 2019. D The EAPC in ASDR of multiple myeloma from 1990 to 2019 by region, for both sexes, combined. ASIR age-standardized incidence rate, ASDR age-standardized death rate, EAPC estimated annual percentage change.

A The ASIR of multiple myeloma in 2019. B The EAPC in ASIR of multiple myeloma from 1990 to 2019. C The ASDR of multiple myeloma in 2019. D The EAPC in ASDR of multiple myeloma from 1990 to 2019. ASIR age-standardized incidence rate, ASDR age-standardized death rate, EAPC estimated annual percentage change.

Although regions with high SDI also consistently had the highest ASDR from 1990 to 2019, the overall trend was downward, with an EAPC of −0.17 (Figs. 5C, D and S9B). And the increasing trend in ASDR was primarily concentrated in low SDI (EAPC = 0.2), low-middle SDI (EAPC = 0.44), middle SDI (EAPC = 0.39), and high-middle SDI (EAPC = 0.3) regions over this period (Fig. 5D). For geographical regions, the highest ASDR of MM in 2019 was observed in North America (3.07 per 100,000 population), Australasia (2.97 per 100,000 population), and Western Europe (2.64 per 100,000 population). The regions with the lowest ASDR were East Asia (0.68 per 100,000 population), Central Asia (0.69 per 100,000 population), and Southeast Asia (0.71 per 100,000 population) (Fig. 5C and Table S4). Almost all regions demonstrated an increasing tendency in ASDR, with the largest increases in Tropical Latin America (EAPC = 1.07), Eastern Europe (EAPC = 1.05), and Central Asia (EAPC = 0.99) (Fig. 5D and Table S4). Among the 204 countries, the United Arab Emirates and Qatar had the most pronounced increases in MM deaths (percent change: 650% to 900%), while Tokelau and Niue had the most significant declines (percent change: −15% to −9%) (Fig. S10B and Table S7). The two countries with higher ASDR were found to be Monaco and Barbados, with rates of 6 to 10 per 100,000 population in 2019 (Fig. 6C). Jamaica (EAPC = 3.96) and Jordan (EAPC = −1.61) have the most significant increasing and decreasing trends respectively in the ASDR of MM (Fig. 6D).

For the correlation analysis of EAPC influencing factors in MM, the EAPC (in ASIR) was positively correlated with the SDI (in 2019) (P = 0.007, ρ = 0.19), but not the ASIR (in 1990) (P = 0.273, ρ = −0.077). Although EAPC (in ASDR) was not significantly associated with ASDR (in 1990) and SDI (in 2019), we found that both ASIR and ASDR were higher in regions with higher SDI levels (Fig. S11), suggesting that areas with higher SDI levels should better perform preventive healthcare and promotion for MM.

Lymphoma burden in different regions and countries

Lymphoma mainly consists of NHL and HL, with NHL being consistently 3–5 times more common than HL. For SDI regions, ASIR in high SDI and high-middle SDI regions remained the highest in NHL and HL (Fig. S12A, B). The ASIR in high SDI regions was 9.93 per 100,000 population for NHL and 2.51 per 100,000 population for HL (Fig. 7A). For geographical regions, the highest and lowest ASIR of NHL in 2019 were observed in Australasia (11.31 per 100,000 population) and Oceania (1.71 per 100,000 population) (Fig. 7A and Table S5), the highest and lowest ASIR of HL in 2019 were observed in Western Europe (2.96 per 100,000 population) and Oceania (0.39 per 100,000 population) (Fig. 7A and Table S6). Except for North America, Australasia, and Western Europe, the ASIR of NHL showed an increasing trend in all regions, with the largest increases in East Asia (EAPC = 3.57), Andean Latin America (EAPC = 2.41), and Eastern Europe (EAPC = 1.77) (Fig. 7C). The regions with the largest increasing trend in the ASIR of HL were the Caribbean (EAPC = 2.4), Asia Pacific (EAPC = 1.21), and Australasia (EAPC = 1.11) (Fig. 7C). Among the 204 countries, Qatar and the United Arab Emirates had the most pronounced increases in NHL incident cases (percent change: 700% to 1000%), while Malawi and Zimbabwe had the most modest increases (percent change: 5% to 10%) (Fig. S13A and Table S7). The Qatar and Republic of Korea had the most pronounced increases in HL incident cases (percent change: 700% to 1000%), while Georgia and Hungary had the most significant declines (percent change: −50% to −30%) (Fig. S14A and Table S7). The two countries with higher ASIR of all lymphoma types were found to be Monaco and San Marino (Figs. 8A and S14B). In addition, Georgia (EAPC = 4.7) and Zimbabwe (EAPC = −2.0) have the most significant increasing and decreasing trends respectively in the ASIR of NHL (Fig. 8B), Cuba (EAPC = 5.86) and Equatorial Guinea (EAPC = −2.42) has the most significant increasing and decreasing trends respectively in the ASIR of HL (Fig. S14C).

A The ASIR of non-Hodgkin lymphoma and Hodgkin lymphoma at a regional level in 1990 and 2019. B The ASDR of non-Hodgkin lymphoma and Hodgkin lymphoma at a regional level in 1990 and 2019. C The EAPC in ASIR of non-Hodgkin lymphoma and Hodgkin lymphoma from 1990 to 2019 by regions, for both sexes, combined. D The EAPC in ASDR of non-Hodgkin lymphoma and Hodgkin lymphoma from 1990 to 2019 by regions, for both sexes, combined. ASIR age-standardized incidence rate, ASDR age-standardized death rate, EAPC estimated annual percentage change.

A The ASIR of Non-Hodgkin lymphoma in 2019. B The EAPC in ASIR of Non-Hodgkin lymphoma from 1990 to 2019. C The ASDR of Non-Hodgkin lymphoma in 2019. D The EAPC in ASDR of Non-Hodgkin lymphoma from 1990 to 2019. ASIR age-standardized incidence rate, ASDR age-standardized death rate, EAPC estimated annual percentage change.

Regarding the death status of lymphoma by SDI regions, high SDI regions consistently have the highest ASDR of NHL from 1990 to 2019, and low SDI regions consistently have the highest ASDR of HL (Fig. S12C, D). For geographical regions, the highest and lowest ASDR of NHL in 2019 was observed in North America (5.27 per 100,000 population) and Oceania (1.7 per 100,000 population) (Fig. 7B and Table S5), the highest and lowest ASDR of HL in 2019 were appeared in Western Sub-Saharan Africa (0.66 per 100,000 population) and Asia Pacific (0.08 per 100,000 population) (Fig. 7B and Table S6). The regions with the largest increasing trend in the ASDR of NHL were South Asia (EAPC = 1.25), East Asia (EAPC = 1.16), and Andean Latin America (EAPC = 1.14) (Fig. 7D). Except for the Caribbean (EAPC = 0.88), the ASDR of HL demonstrated a decreasing tendency in all regions, with the largest decreases in East Asia (EAPC = −4.68), Central Europe (EAPC = −3.4), and Western Europe (EAPC = −2.42) (Fig. 7D). Among the 204 countries, Qatar and the United Arab Emirates had the most significant increases in all lymphoma types deaths (Figs. S13B, S14D, and Table S7). The two countries with higher ASDR of NHL were found to be Monaco and Afghanistan, with rates of 14 to 16 per 100,000 population in 2019 (Fig. 8C). The two countries with higher ASDR of HL were found to be Pakistan and Nigeria, with rates of 1.1 to 1.3 per 100,000 population in 2019 (Fig. S14E). In addition, Georgia (EAPC = 4.54) and Syrian Arab Republic (EAPC = −2.46) has the most significant increasing and decreasing trends respectively in the ASDR of NHL (Fig. 8D), Cuba (EAPC = 3.96) and China (EAPC = −4.77) has the most significant increasing and decreasing trends respectively in the ASDR of HL (Fig. S14F). For Qatar and the United Arab Emirates, which had the largest fluctuations in the number of cases, further analysis showed that the huge changes in population structure were an important reason for the fluctuations in the number of cases (Fig. S21).

For the correlation analysis of EAPC influencing factors in lymphoma, the EAPC was negatively connected with ASIR (P < 0.001, ρ = −0.342) and ASDR (P < 0.001, ρ = −0.444) in NHL (Fig. S15), the EAPC was negatively associated with ASDR (P < 0.001, ρ = −0.417) and SDI (in 2019) (P < 0.001, ρ = −0.431) in HL (Fig. S16). In addition, we found that in areas with higher SDI levels, ASIR and ASDR in NHL were higher, ASIR in HL was higher, and only ASDR in HL showed a decrease, suggesting that areas with higher SDI levels should better perform preventive healthcare and promotion for NHL.

Contribution of high BMI burden to death from hematologic malignancies

Leukemia was the leading cause of death for hematologic malignancies at the global and regional scales, followed by NHL, MM, and HL, accordingly for 45.8%, 34.9%, 15.5%, and 3.8% of total deaths in 2019, respectively (Fig. S17A). High BMI is the main cause of diverse metabolic disorders, the public health issues associated with high BMI have been recognized for a long time and are becoming increasingly important [22,23,24,25]. Our analysis found that the proportion of mortality risk attributable to high BMI in 2019 was significantly higher in all regions than in 1990. The proportion of deaths attributed to high BMI had a strong positive correlation with SDI levels, and the proportion of leukemia, MM, and lymphoma in low SDI regions was 2.4%, 3.7%, and 2.9%, respectively, in 2019, lower than in other SDI regions (Fig. S17B). Meanwhile, the region with high SDI consistently had the highest risk of death attributable to high BMI from 1990 to 2019 (Fig. S17C, E). Regarding the effect of gender and age, the proportion of deaths attributed to high BMI was higher in females with leukemia and MM in all regions (Fig. S19A). Globally, the highest risk of death from hematologic malignancies (including leukemia, MM, and NHL) attributed to high BMI in 2019 was in the 50 to 69 age group (Fig. S19B). Table S8 shows the details of the risk of death attributed to high BMI at the national level, Congo males (15.9%), Canadian males (15.2%), and Colombia males (17.6%) account for the highest percentages of leukemia, MM, and NHL respectively, in 2019.

Contribution of occupational carcinogens burden to death from leukemia

Exposure to benzene and formaldehyde in occupational carcinogens is a known risk factor for leukemia [26]. Globally, the proportion of leukemia deaths attributable to occupational exposure to benzene and formaldehyde in 2019 was 0.56% and 0.18%, respectively. The proportion of deaths attributed to occupational carcinogens was always the highest in middle SDI regions, and the proportion of deaths from occupational benzene exposure changed from the lowest in the low SDI regions to high SDI regions from 1990 to 2019 (Fig. S18A, B). For all leukemia subtypes, the largest risk of death attributed to occupational exposure to benzene and formaldehyde globally in 2019 was CML. The regions with the highest proportion of leukemia deaths attributable to occupational carcinogens in 2019 were Andean Latin America and Central Latin America (Fig. S18C). Regarding the effect of gender, the proportion of deaths attributable to occupational exposure to benzene in CML and CLL was predominant in males, while AML and ALL were predominant in females, and occupational exposure to formaldehyde was more common in males with all types of leukemia (Fig. S20). Ireland and Dominica are at high risk of occupational exposure to benzene and formaldehyde, the detailed death risk caused by occupational carcinogens for all types of leukemia at the national level is shown in Table S9.