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Purpose Despite an increasing understanding of the pathology and genetics of non-Hodgkin lymphoma (NHL), global reports on variations in the incidence of NHL remain limited in their number and scope. Methods To provide a situation analysis, national incidence estimates for NHL in 185 countries for the year 2018 were obtained from the GLOBOCAN database. We also used recorded incidence data from Cancer Incidence in Five Continents (CI5) plus for years of diagnosis 1980–2012 to examine temporal trends. Results NHL ranked as the 5th to 9th most common cancer in most countries worldwide, with almost 510,000 new cases estimated in 2018. Observed incidence rates of NHL 2008–2012 varied markedly by world region: among males, rates were highest among Israel Jews [age-standardized (world) rate of 17.6 per 100,000), Australia (15.3), US whites (14.5), Canada (13.7), and Portugal (13.3)]. Where data were available, most populations exhibited stable or slightly increasing incidence rates; in North America, parts of Europe, and Oceania the rising incidence rates were generally observed until the 1990s, with a stabilization seen thereafter. Conclusion Marked variations in NHL incidence rates remain in populations in each world region. Special attention should be given to further etiological research on the role of endemic infections and environmental exposures, particularly in Africa, Asia, and Latin America. To permit internationally comparable statistics, an equal focus on addressing the quality of hematological information in population-based registries is also warranted.
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Vol.:(0123456789)
1 3
Cancer Causes & Control
https://doi.org/10.1007/s10552-019-01155-5
ORIGINAL PAPER
Global patterns andtrends intheincidence ofnon-Hodgkin
lymphoma
AdalbertoMiranda‑Filho1 · MarionPiñeros1· ArianaZnaor1· RafaelMarcos‑Gragera2· EvaSteliarova‑Foucher1·
FreddieBray1
Received: 22 August 2018 / Accepted: 6 March 2019
© Springer Nature Switzerland AG 2019
Abstract
Purpose Despite an increasing understanding of the pathology and genetics of non-Hodgkin lymphoma (NHL), global
reports on variations in the incidence of NHL remain limited in their number and scope.
Methods To provide a situation analysis, national incidence estimates for NHL in 185 countries for the year 2018 were
obtained from the GLOBOCAN database. We also used recorded incidence data from Cancer Incidence in Five Continents
(CI5) plus for years of diagnosis 1980–2012 to examine temporal trends.
Results NHL ranked as the 5th to 9th most common cancer in most countries worldwide, with almost 510,000 new cases
estimated in 2018. Observed incidence rates of NHL 2008–2012 varied markedly by world region: among males, rates were
highest among Israel Jews [age-standardized (world) rate of 17.6 per 100,000), Australia (15.3), US whites (14.5), Canada
(13.7), and Portugal (13.3)]. Where data were available, most populations exhibited stable or slightly increasing incidence
rates; in North America, parts of Europe, and Oceania the rising incidence rates were generally observed until the 1990s,
with a stabilization seen thereafter.
Conclusion Marked variations in NHL incidence rates remain in populations in each world region. Special attention should
be given to further etiological research on the role of endemic infections and environmental exposures, particularly in Africa,
Asia, and Latin America. To permit internationally comparable statistics, an equal focus on addressing the quality of hema-
tological information in population-based registries is also warranted.
Keywords Lymphoid neoplasms· Non-Hodgkin lymphoma· Population-based cancer registries· Global epidemiology
Introduction
Non-Hodgkin lymphoma (NHL) ranks as the tenth and
twelfth most frequent cancer in males and females world-
wide, respectively, with an estimated 509,590 new cases and
248,724 deaths in 2018 [1]. These malignancies arise from
the malignant transformation of mature and immature cells
of immune system, affecting either B lymphocytes (B cells,
representing around 86% of all NHL), and a smaller propor-
tion of T- and natural killer (NK) cells (14% in developing
regions) [2]. The classification of NHL is complex; knowl-
edge of both clinical features and genetic abnormalities is
essential to distinguish entities and provide accurate diag-
noses [3]. A large proportion of NHL diagnoses (e.g., 35%
in the UK) occur at older ages, with a peak incidence rate
at ages at 75 or older [4]; the frequency of NHL subtypes
varies by country [5]. Five-year survival estimates of 80%
are observed in high-income settings but vary according to
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s1055 2-019-01155 -5) contains
supplementary material, which is available to authorized users.
* Adalberto Miranda-Filho
mirandaa@fellows.iarc.fr
1 Section ofCancer Surveillance, International Agency
forResearch onCancer, 150 Cours Albert Thomas,
69372LyonCEDEX08, France
2 Epidemiology Unit andGirona Cancer Registry (UERCG),
Oncology Coordination Plan, Department ofHealth,
Autonomous Government ofCatalonia, Catalan Institute
ofOncology (ICO), Girona Biomedical Research Institute
(IDIBGI), University ofGirona, Girona, Spain
Cancer Causes & Control
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subtype and age; survival is markedly lower in low- and
middle-income countries (LMIC) [6].
The incidence of NHL is associated with considerable
geographic and temporal variability worldwide, although
this inherent aetiological heterogeneity has helped uncover
few risk factors. Genetic determinants, including a family
history of NHL, have been implicated as a cause of NHL, as
have certain lifestyle and environmental factors, including
obesity and certain occupational exposures [7]. It has been
established that infections, particularly those associated with
Hepatitis C virus (HCV), Epstein–Barr virus (EBV), and
Helicobacter pylori (H. pylori) can increase or modulate
the risk of NHL [8]. While the risk of NHL is higher among
HIV-infected persons as a result of immunosuppression
[9], declines in the elevated risk have been reported from
some high-income settings in the post-antiretroviral therapy
(ART) era [10].
Even with an increasing understanding of the pathol-
ogy and genetics of NHL, global reports on the patterns
and trends of NHL remain rather limited in number and
scope. In part, this may reflect the underlying complexity
of evolving classification and diagnostic criteria that cancer
registries are tasked to comply with. This global overview
seeks to identify distinct patterns of incidence that may serve
to generate hypotheses for further investigation, as well as
inform cancer control. We focus on geographical and tem-
poral variations in NHL according to country, sex, and age
using the recorded data from population-based cancer reg-
istries (PBCR), alongside national estimates compiled at the
International Agency for Research on Cancer (IARC).
Methods
Data sources andpopulation
Estimates of NHL incidence for 185 countries in the year
2018 were extracted from IARC’s GLOBOCAN database
[1]. The methods of estimation are based on the most reli-
able sources of cancer incidence and mortality data avail-
able at national or subnational level. A detailed account of
the methods is provided by Ferlay and colleagues elsewhere
[11]. We examined the age profile of NHL according to the
Human Development Index (HDI) based on the predefined
cut-points: low (HDI < 0.5), medium (0.5 ≤ HDI < 0.8), high
(0.8 ≤ HDI < 0.9), and very high (HDI ≥ 0.9) [12].
The prevalence of HIV among adults aged 15 to 49 in 128
countries for the year 2010 was extracted from the WHO
Global Health Observatory [13], representing the percent-
age of the national population aged 15–49years and living
with HIV. These are visually correlated with age-standard-
ized NHL incidence rates as estimated in GLOBOCAN for
the year 2018 [11].
New cases of NHL and population-at-risk data were
extracted from successive volumes of Cancer Incidence in
Five Continents (CI5), a compendium of high-quality data
from population-based cancer registries (PBCR) worldwide
[14]. We extracted recorded incidence and population data
as reported in the latest volume of CI5 (volume XI) for 343
cancer registries in 62 countries worldwide, predominantly
for the years of diagnosis 2008–2012. We examined tem-
poral patterns of NHL in selected countries using the long-
standing high-quality cancer registries that were included in
the last six volumes of CI5 covering the period from 1980 to
2012, based on the data provided by population-based cancer
registries (PBCR) worldwide [15]. In the absence of national
coverage, an existing subnational registry or a pool of such
registries represented the relevant country (http://ci5.iarc.fr/
CI5-XI/Pages /regis try_summa ry.aspx).
To ensure comparability in the incidence between regis-
try populations in CI5, morphological groups of the Inter-
national Classification of Diseases for Oncology (ICD-O,
2000) were converted to the 10th revision of the Interna-
tional Classification of Diseases (ICD-10) and coded to C82-
86, C96 [16] as shown in Appendix I in supplementary file.
In order to ensure consistency in the included tumor types
between the successive volumes of CI5 malignant lym-
phoma, small B lymphocytic, NOS (9,670) was included in
our grouping of NHL, whereas NHL B-cell chronic lympho-
cytic leukemia/small lymphocytic lymphoma (9,823) was
excluded.
Statistical analyses
Age-specific incidence rates per 100,000 person-years were
estimated by country and sex and presented according to
HDI levels. Age-standardized rates (ASR) were weighted
using the World Standard population [17] and presented in
tabular form with corresponding 95% confidence intervals
[18]. The ASR for 2018 and its ranking in relation to other
cancer types were depicted in global maps. Time trends in
the ASR are presented by calendar year and sex. Analyses
were undertaken using R software 3.3.3 [19].
Results
Estimated incidence 2018
Figure1a illustrates the global variation in NHL incidence
rates in 2018 for both sexes combined; the corresponding
ASR by world region and sex are shown in Table1. Overall,
rates were consistently higher among males compared with
females, with sex ratios varying from 1.1 to 1.8 by region.
Among men, the highest incidence rates were observed in
Australia and New Zealand (16.4 per 100,000), Northern
Cancer Causes & Control
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America (14.8 per 100,000), and in Northern Europe (13.5
per 100,000), while the lowest rates were seen in Middle
Africa (3.2 per 100,000) and Central America (4.60 per
100,000). A similar geographical pattern was observed in
females, with the highest rates observed in Northern Amer-
ica (10.4 per 100,000) and the lowest in Middle Africa (2.8
per 100,000). Figure1b shows the ranking of NHL by fre-
quency of new cases relative to other major cancers. Marked
differences were seen between and within regions world-
wide, with NHL ranking as the 4th leading cause of cancer
occurrence in Oman, Egypt, Bahrain, Qatar, and Sudan. In
a further 87 countries, NHL was the fifth to ninth most com-
mon cancer.
Observed incidence circa2008–2012
Figure2 shows the recorded national or subnational NHL
incidence rates circa 2008–2012 by country according to
HDI level. The number of cases and corresponding popula-
tions covered by the registries are tabulated in Table2. Inci-
dence rates of NHL varied tenfold, with NHL rates among
males highest in Israel Jews (17.6 per 100,000), Australia
Data source: Globocan 2018
Map production: IARC
World Health Organization
© WHO 2016. All rights reserved
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever
on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities,
or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate borderlines
for which there may not yet be full agreement.
<3.0
3.0 - 4.5
4.6 - 5.8
5.9 - 8.5
>8.5
<5th
10th or greather
5th - 9th
(A)
(B)
Fig. 1 a Age-standardized (world) incidence rates (quintiles) of non-Hodgkin lymphoma, both sexes; b ranking of non-Hodgkin lymphoma by
frequency of new cases relative to other common cancers, both sexes (Source: GLOBOCAN, 2018)
Cancer Causes & Control
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(15.3 per 100,000), US whites (14.5 per 100,000), Canada
(13.7 per 100,000), and Portugal (13.3 per 100,000). Among
females, similar patterns were observed with elevated rates
in Israel Jews (13.0 per 100,000) and Australia (12.3 per
100,000), followed by US whites (10.3 per 100,000) and
Canada (10.0 per 100,000). In males, incidence rates were
lowest in South Africa (1.6 per 100,000), Vietnam, and India
(3.5 and 3.6 per 100,000, respectively), with an analogous
profile observed among females, but with the lowest rates
ranging between 1 and 2 per 100,000.
Temporal patterns 1980–2012
Time trends in the NHL incidence rates by sex in selected
countries circa 1980–2012 are shown in Fig.3. In the major-
ity of countries, trends in incidence rates were either stable
or decreases among both males and females. The United
States, Canada, Australia, and New Zealand all exhib-
ited a rising incidence trend until the 1990s, followed by
a stabilization thereafter. Similar temporal patterns were
observed in Europe (e.g., in Austria, Croatia, Germany, Italy,
France, Spain, and Switzerland) and Asia (e.g., in Japan,
Korea, India, Philippines, and Thailand).
HIV prevalence, Human Development Index,
andNHL incidence
Figure4a presents a graphic representation of HIV preva-
lence in 2010 and the estimated incidence of NHL in 2018,
both sexes combined. Figure4b shows the estimated inci-
dence of NHL in 2018, and the Human Development Index,
both sexes combined. Higher rates of NHL were common in
countries classified as very high HDI, while many countries
classified as low and medium HDI presented lower incidence
rates. The linear relation between the magnitude of the NHL
incidence rates and level of HDI appears confined to very
high HDI countries.
Discussion
In this population-based study, we provide a comprehen-
sive review of NHL incidence using national estimates in
185 countries for the year 2018, complemented by a more
detailed exposition of geographical and temporal variations
based on either national or subnational high-quality data
from population-based cancer registries included in the Can-
cer Incidence in Five Continents series. We report distinct
geographic patterns in NHL incidence by world region, HDI
level, sex, and age, with rates consistently higher among
males than females. As a disease entity, NHL ranks as the
fourth leading cause of cancer occurrence in Oman, Egypt,
Bahrain, Qatar, and Sudan, and as the fifth to ninth most
common cancer in a further 87 countries of the world. The
incidence trends were stable or increasing in most countries
where data were available; in the populations representing
North America, Europe, and Oceania, a pattern of rising
incidence until the 1990s, followed by a stabilization, was
commonly observed.
NHL comprises a wide range of cancers of the immune
system ranging from indolent to aggressive types [3] for
which the extent of clinical resources are a major factor in
assuring accurate diagnoses. The observed heterogeneity of
NHL incidence rates by human development level seen in
this study can thus be postulated to be driven by disparities
in health system infrastructure and the delivery of cancer
services, and consequently, the availability of diagnostic and
treatment facilities for cancer [20]. Diagnostic precision of
NHL requires excisional biopsy, followed by a pathologist
examination and the final classification, based on morphol-
ogy, immunophenotype, genetic, and clinical features [21,
22]. Such a process may be unattainable at present in some
Table 1 Estimated number of cases and age-standardized (world)
incidence rates of non-Hodgkin lymphoma by world region and sex.
Source: GLOBOCAN, 2018
asr age-standardized incidence rate (world)
a Male:female rate ratio
Males Females M:Fa
Cases ASR Cases ASR
World 284,713 6.7 224,877 4.7 1.4
Africa
Eastern Africa 8,489 5.7 6,758 4.1 1.4
Middle Africa 1,848 3.2 1,609 2.8 1.1
Northern Africa 9,136 8.9 7,297 6.8 1.3
Southern Africa 2,047 7.3 1,981 5.8 1.3
Western Africa 5,512 5.0 3,910 3.2 1.6
Americas
Northern America 44,838 14.8 36,523 10.4 1.4
Caribbean 1,417 5.7 1,265 4.6 1.2
Central America 3,908 4.6 3,147 3.4 1.4
South America 16,529 7.2 13,144 4.8 1.5
Asia
Eastern Asia 68,990 5.5 57,274 4.3 1.3
South-Eastern Asia 19,716 6.2 13,334 3.8 1.6
South Central Asia 27,052 3.0 16,572 1.8 1.7
Western Asia 8,462 7.1 6,295 5.1 1.4
Europe
Eastern Europe 11,628 5.9 12,179 4.4 1.3
Northern Europe 12,989 13.5 10,711 9.7 1.4
Southern Europe 14,143 10.0 12,187 7.4 1.4
Western Europe 23,627 12.5 17,654 7.9 1.6
Oceania
Australia/New Zealand 4,030 16.4 2,815 10.4 1.6
Cancer Causes & Control
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LMIC, where advanced diagnostic techniques are not availa-
ble. The reported NHL incidence may thus also be subject to
some misclassification and under-reporting in these settings.
The heterogeneity of NHL incidence rates and trends is
also related to the prevalence and distribution of the under-
lying known and putative risk factors [20]. In Africa, parts
of South America, and Asia, the estimated incidence rates
could in part reflect the infectious origin of NHL. There is
accumulating evidence that EBV is linked to the etiology
of NHL [23]. EBV-positive diffuse large B-cell lymphoma
(DLBCL) is a category of NHL subtype included in the
WHO Blue Books since 2008 and represents between 5 and
15% of all DLBCLs worldwide [24]. These cases are more
common in the elderly, as they relate to the process of aging
that causes alterations in the immune system and the pro-
tracted latency of EBV infection [25]. Several other T-cell
and NK-cell NHL are classified as EBV-positive; these are
rarer types, that have been reported to occur more commonly
in less-resourced settings in Asia and among indigenous
populations in Latin America [26].
Males
Females
Low HDI Medium HDI
High HDI
Human Development Index
Very high HDI
1.61.0
3.52.3
3.62.1
4.33.1
4.53.2
4.52.9
4.83.4
5.03.8
5.13.6
5.34.0
5.45.1
5.54.2
5.53.9
5.75.0
5.84.1
6.05.9
6.46.1
6.44.6
6.54.1
6.63.2
6.64.8
6.75.1
6.95.4
7.05.2
7.25.1
7.25.2
7.45.6
7.55.4
7.67.2
7.65.9
7.76.0
7.76.5
7.75.1
7.96.1
8.05.2
8.76.5
8.76.1
9.05.8
9.14.9
9.26.6
9.47.3
9.
78
.6
10.26.8
10.36.9
10.
47
.4
10.47.0
10.
97
.3
14.5 10.0
11.3 10.6
11.
57
.9
11.
68
.8
12.
08
.6
12.
19
.1
12.
27
.9
12.
38
.2
12.
59
.0
12.
59
.0
12.
98
.9
12.
98
.6
13.
19
.2
13.
37
.7
13.
79
.8
11.3 7.5
15.3 11.1
15.3 10.3
17.6 13.0
16.7 12.3
20 18 16 14 12 10 8 6 4 2 0 2 4 6 8 10 12 14 16 18
South Africa
India
Viet Nam
Algeria
Philippines
Ukraine
China
Bulgaria
Russian Federation
Chile
Jordan
Kenya
Belarus
Jamaica
Poland
Saudi Arabia
Kuwait
Thailand
Republic of Korea
Iran (2008-2011)
Argentina
Malaysia
Latvia
Uganda
Turkey
Costa Rica
Croatia
Lithuania
Seychelles
Colombia
Slovakia
Ecuador
Bahrain
Slovenia
Brazil
Czech Republic
Japan
Estonia
Qatar
Austria
Puerto Rico
Cyprus
Uruguay
Brunei Darussalam
Spain
Germany
Iceland
USA: White
Malta
Switzerland
Peru
Belgium
Ireland
France
Netherlands
United Kingdom
Norway
Italy
Denmark
New Zealand
Portugal
Canada
USA: Black
Zimbabwe (2010-2012)
Australia
Israel: Jews
Israel
Age standardised incidence rates per 100000
20
Fig. 2 Age-standardized (world) incidence rates of non-Hodgkin lymphoma by world region and HDI in males and females circa 2008–2012
(Source: Cancer Incidence in Five Continents Volume XI)
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Table 2 Number of new cases of NHL, age-standardized (world) incidence rates (ASR), and 95% confidence intervals, based diagnoses circa
2008–2012. Source: Cancer Incidence in Five Continents, Volume XI
Number of
registries
Population
covered in
million
Population
covered (%)
Males Females M:F
Cases ASR 95% CI Cases ASR 95% CI
Africa
Zimbabwe (2010–2012) 1 4.4 30.9 202 15.3 12.8 17.8 181 11.0 9.2 12.9 1.4
Seychelles 1 0.1 80.3 13 7.5 3.3 11.8 14 7.2 3.2 11.2 1.1
Uganda 1 2.2 6.6 256 6.9 5.8 8.2 203 5.1 4.2 6.2 1.3
Kenya 1 3.1 7.6 214 5.4 4.5 6.5 154 4.1 3.3 5.1 1.3
Algeria 2 2.4 6.6 223 4.2 3.7 4.9 171 3.1 2.6 3.7 1.4
South Africa 1 1.0 2.1 24 1.5 0.9 2.2 27 1.0 0.6 1.4 1.5
America and Caribbean
US: white (NPCR)a1 232.5 95 132,200 14.4 14.4 14.6 109,428 10.0 7.4 7.6 1.4
Canada 12 26.1 76.8 14,051 13.71 13.5 14 11,591 9.8 9.7 10 1.4
Peru 1 5.6 19 1,480 11.6 11 12.2 1,327 8.7 8.3 9.2 1.3
US: black (NPCR)a1 21.5 51 12,007 11.1 11.1 11.4 10,240 7.4 10 10.1 1.5
Uruguaya1 3.4 100 1,103 10.2 9.6 10.9 949 6.8 6.3 7.3 1.5
Puerto Ricoa1 3.8 100 1,250 9.4 8.9 10 1,200 7.3 6.9 7.8 1.3
Brazil 6 3.8 1.9 738 7.9 7.4 8.6 635 5.2 4.8 5.7 1.5
Ecuador 5 6.0 40.2 1,181 7.6 7.2 8.2 1,095 6.5 6.1 7 1.2
Colombia 4 4.1 9.0 774 7.6 7.1 8.2 772 5.9 5.5 6.3 1.3
Costa Rica (2008–2011)a1 3.6 79.8 623 7.1 6.6 7.7 465 5.1 4.7 5.6 1.4
Argentina 5 5.2 12.5 902 6.6 6.2 7.1 785 4.8 4.5 5.2 1.4
Jamaica 1 0.5 18.8 72 5.6 4.3 7 73 5.0 3.8 6.2 1.1
Chile 4 1.7 10.1 263 5.3 4.7 6 227 3.9 3.4 4.5 1.3
Asia
Israela4 7.6 100 3,583 16.7 16.1 17.3 3,133 12.3 11.9 12.8 1.4
Israel: Jewsa4 5.7 75.4 3,155 17.5 16.9 18.2 2,773 12.9 12.5 13.5 1.4
Brunei Darussalam 1 0.2 47.4 36 10.2 6.8 13.8 30 6.9 4.4 9.5 1.5
Qatar 1 0.2 1.25 40 9.1 6.1 12.2 24 4.9 2.8 7.1 1.8
Japan 9 28.2 22.1 13,058 8.7 8.6 8.9 10,960 6.0 5.9 6.2 1.4
Bahrain 1 1.2 100 91 7.7 6.1 9.4 61 5.0 3.7 6.5 1.5
Turkey 8 12.1 16.8 2,321 7.1 6.9 7.5 1,826 5.0 4.8 5.3 1.4
Iran (2008–2011) 1 1.4 1.8 182 6.5 5.5 7.6 92 3.1 2.5 3.9 2.1
Malaysia 4 0.9 3.1 157 6.7 5.6 7.8 125 5.1 4.2 6.1 1.3
Thailand 7 11.6 17.3 2,045 6.4 6.1 6.7 1,692 4.5 4.3 4.8 1.4
Kuwait 3 3.6 100 416 6.3 5.5 7.2 251 6.1 5.2 7 1.0
Republic of Korea 8 49.6 100 14,203 6.4 6.4 6.6 10,437 4.1 4.1 4.2 1.6
Saudi Arabia 1 21.4 77.7 558 5.9 5.4 6.5 456 5.8 5.3 6.5 1.0
Jordan 1 6.1 3.2 590 5.3 4.9 5.9 517 5.1 4.6 5.6 1.1
China 36 63.0 4.7 11,291 4.8 4.7 4.9 8,534 3.4 3.4 3.5 1.4
Philippines 2 14.0 15.0 1,195 4.4 4.2 4.8 1,063 3.2 3 3.4 1.4
India 16 47.3 3.8 4,099 3.4 3.4 3.6 2,648 2.3 2.3 2.4 1.5
Vietnam 1 6.0 6.8 421 3.6 3.2 4 314 2.1 1.9 2.4 1.7
Eastern Europe
Czech Republic 1 10.5 100 3,540 8.7 8.4 9 3,484 6.4 6.2 6.7 1.3
Slovakiaa1 5.4 100 795 7.6 7.1 8.2 812 6.0 5.5 6.5 1.3
Poland 5 11.9 31.2 2,334 5.7 5.5 6 2,201 4.0 3.9 4.3 1.4
Belarus 1 9.5 100 1,564 5.5 5.3 5.8 1,716 3.9 3.7 4.1 1.4
Bulgariaa1 7.5 100 1,398 5.0 4.8 5.3 1,311 3.7 3.5 4.0 1.3
Russian Federation 4 8.6 6.0 1,259 5.1 4.8 5.4 1,326 3.5 3.4 3.8 1.4
Cancer Causes & Control
1 3
Assessments of the causal association between HIV and
NHL at the global level through ecologic analyses are sub-
ject to well-known biases and any interpretation should be
undertaken with caution. The observation that countries
with a low prevalence of HIV in 2010 had quite variable
NHL incidence rates may relate to the poorer survival of
HIV-infected patients in LMIC, and the possibility that
many patients die before they would have developed NHL.
HIV infection plays an important role in the etiology of
NHL, and it has been estimated that around 5–10% of HIV-
infected patients develop lymphomas [27], and thus coun-
tries with a high prevalence of HIV, such as Uganda (7%,
data not shown), and Zimbabwe (15.5%, data not shown),
the incidence of NHL is expected to be elevated, even in the
presence of some misclassification. As NHL is an AIDS-
defining cancer, incidence rates may have declined upon
the introduction of the antiretroviral treatment, notably in
these Sub-Saharan Africa countries that have been among
the most impacted by the HIV epidemic [28, 29].
Globally, we observed some disparities in the temporal
patterns of NHL incidence in different countries. An expla-
nation for the slight increases in incidence in certain Asian
countries including the Republic of Korea, and Japan is not
clear but may be partially linked to better diagnosis and
complete registration, as well as environmental exposures
and lifestyle factors [30]. HBV has been linked to NHL inci-
dence in Korea [31] and an increasing incidence of NHL
observed at older ages, while HBV prevalence is decreas-
ing at younger ages [32]. A high proportion (50–60%) of
adult T-cell leukemia/lymphoma among NHL in Japan [33]
illustrates the importance of HTLV-I infection on NHL
incidence. The high prevalence of HTLV-1 recorded in
Japan, and certain populations in Africa, South America,
and Caribbean [34] may contribute to the observed elevated
M:F rate ratio male:female
a National registry
Table 2 (continued)
Number of
registries
Population
covered in
million
Population
covered (%)
Males Females M:F
Cases ASR 95% CI Cases ASR 95% CI
Ukrainea1 45.8 100 6,142 4.5 4.4 4.6 5,628 2.9 2.8 3.0 1.5
Northern Europe
Denmarka1 5.5 100 3,005 12.9 12.4 13.4 2,339 8.6 8.2 9.0 1.5
United Kingdom 13 62.8 100 92,940 12.4 12.4 12.6 78,908 9.0 8.9 9.1 1.4
Norwaya1 4.9 100 2,447 12.5 12 13.1 1,949 8.9 8.5 9.4 1.4
Ireland 1 4.5 100 1,843 12.1 11.6 12.7 1,541 9.1 8.6 9.6 1.3
Iceland 1 0.3 100 122 10.8 8.8 12.9 92 7.3 5.7 8.9 1.5
Estoniaa1 1.3 100 411 8.9 8.1 9.9 426 5.8 5.2 6.5 1.5
Lithuaniaa1 3.1 100 808 7.5 7 8.1 923 5.3 5 5.8 1.4
Latvia (2010–2012)a1 2.0 100 271 6.8 6 7.8 337 5.3 4.7 6.1 1.3
Southern Europe
Portugal 1 0.2 1.9 86 13.2 10.4 16.1 60 7.6 5.6 9.8 1.7
Italy 36 24.6 41.5 13,692 12.8 12.6 13.1 11,684 8.9 8.7 9.1 1.4
Malta 1 0.4 100 179 11.2 9.5 13.1 198 10.6 9 12.2 1.1
Spain 14 10.3 22.3 4,230 10.3 10 10.7 3,562 7.3 7.1 7.7 1.4
Cyprusa1 0.8 75.4 285 9.6 8.5 10.8 296 8.6 7.6 9.7 1.1
Sloveniaa1 2.0 100 715 7.9 7.3 8.6 711 6.1 5.6 6.7 1.3
Croatiaa1 4.4 100 1,201 7.4 7 7.9 1,201 5.5 5.2 6.0 1.3
Western Europe
Netherlandsa1 16.6 100 8,306 12.2 12 12.5 6,496 8.2 8 8.5 1.5
France 18 11.9 18.3 5,804 12.1 11.8 12.5 4,713 7.8 7.6 8.1 1.5
Belgiuma1 10.8 100 5,338 12.0 11.7 12.4 4,596 8.5 8.3 8.9 1.4
Switzerland 9 4.4 56.2 2,104 11.5 11 12.1 1,767 7.8 7.4 8.3 1.5
Germany 9 53.1 65.3 25,398 10.3 10.2 10.5 21,552 7.0 6.9 7.1 1.5
Austriaa3 8.4 100 3,746 9.1 8.8 9.5 3,405 6.5 6.3 6.8 1.4
Australia/New Zealand
Australiaa9 21.9 100 25,682 15.3 15.1 15.5 19,526 10.3 10.2 10.5 1.5
New Zealand 3 4.4 100 2,112 13.1 12.5 13.7 1,682 9.1 8.7 9.7 1.4
Cancer Causes & Control
1 3
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Australia
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Austria
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Brazil
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Canada
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
China
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Colombia
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Costa Rica
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Croatia
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Denmark
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Ecuador
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Estonia
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
France
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Germany
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
India
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Ireland
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Italy
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Japan
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Lithuania
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Netherlands
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
New Zealand
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Norway
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Philippines
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Poland
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Republic of Korea
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Slovakia
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Slovenia
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Spain
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Switzerland
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Thailand
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,000
1980 1985 1990 1995 2000 2005 2010
Year
Uganda
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,00
0
1980 1985 1990 1995 2000 2005 2010
Year
United Kingdom
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,00
0
1980 1985 1990 1995 2000 2005 2010
Year
USA: Black
1
1.5
2
2.5
3
3.5
4
5
7
10
12
15
20
25
30
35
40
50
60
Age standardized incidence rate per 100,00
0
1980 1985 1990 1995 2000 2005 2010
Year
USA: White
Age-standardised incidence rates per 100000 in males
Age-standardised incidence rates per 100000 in females
Fig. 3 Time trends in non-Hodgkin lymphoma incidence rates (age-standardized rates-world), in males and females 1980–2012 [Source: Cancer
Incidence in Five Continents plus (1980–2012)]
Cancer Causes & Control
1 3
incidence rates of NHL, that are likely modulated by other
factors. Perry etal. [35] found marked differences in the
frequencies of NHL subtypes in developed and develop-
ing regions; for instance, a lower frequency of B-cell NHL
and higher frequency of T- and NK-cell NHL were seen in
developing regions, while a higher frequency of Burkitt lym-
phoma was observed in parts of Central and South America
and Africa.
Our common observation of a rising incidence in North
America, parts of Europe, and Oceania until the 1990s with
a stabilization thereafter is confirmed by other reports.
van Leeuwen etal. [36] reported NHL incidence increas-
ing during the period 1982–1996, with stable trends seen
from 1997 to 2006. In Spain, Marcos-Gragera etal. [37]
found an attenuation in NHL incidence after 1996, that was
hypotheses as partly explained by the decrease in incidence
of AIDS-related lymphomas among young adults and other
factors. Adamson etal. [38] described the trends in inci-
dence of 13 European countries until 2000, observing an
increase in the number of NHL registration in all countries
of the study [38].
While a higher incidence of NHL has been consistently
reported In North America and other developed countries
and one that has been linked to the HIV epidemic [37, 39],
the temporal patterns of NHL, must be interpreted with cau-
tion. The improvements in cancer registration, as well as the
changing classification may have impacted on the observed
patterns over time. The Revised European-American Clas-
sification of lymphoid Neoplasms (REAL) became the basis
for the WHO Classification of Tumours of Haematopoietic
and Lymphoid Tissue when originally published in 2001, and
represented a global consensus on hematopoietic classifica-
tion that likely coincides with some of the period-related
changes in the trends observed in this study.
There are also a number of limitations in our study. The
robustness of the national estimates in GLOBOCAN var-
ies by country depending on the availability of high-quality
incidence and mortality data. International comparisons
based on the observed data from PBCR may be subject to
varying coding practices between the registries included in
the CI5 series and within each institution over time. It is
also important to note that incidence data are derived from
subnational cancer registries in many countries, and some
will be more representative of the national profile and time
trends than others. While the registries included in CI5 are
deemed of high quality by an appointed editorial board,
there remains the need to improve the accuracy of informa-
tion on hematological malignancies as defined in the pathol-
ogy reports abstracted at the PBCR. Not all cancer registries
provide specific morphological diagnosis for a sufficiently
large proportion of cases as to be included in analyses by
histological subgroup. Although such analyses may help
interpreting the results in the areas with high-quality pathol-
ogy services, the definition of subtypes may be subjected to
regional variation.
An important strength of our study is the global coverage
assembled via successive volumes of CI5 spanning 30years,
alongside national estimates for all world areas for the year
(A) (B)
Low HDIMedium HDI
High HDI
Human Development Index
Very high HDI
0
2
4
6
8
10
12
14
0.1
0.2
0.3
0.4
0.5
0.7
1
2
3
5
7
10
20
30
HIV prevalence
Age standardised (World) incidence rate per 100000
0
2
4
6
8
10
12
14
0.4
0.5
0.6
0.7
0.8
0.9
Human Development Index
Age standardised (World) incidence rate per 100000
Fig. 4 a Prevalence of HIV among adults aged 15–49 years old
in 2010 (log scale) and age-standardized incidence rates 2018 by
Human Development Index; b age-standardized incidence rates and
Human Development Index (natural scale) by the prevalence of HIV
among adults aged 15–49years. The diameter of the circles is rela-
tive to the magnitude of the HIV prevalence and their color represents
HDI level (Sources: GLOBOCAN 2018, WHO Global Health Obser-
vatory, United Nations Development Programme)
Cancer Causes & Control
1 3
2018 from the GLOBOCAN database that can be inspected
at IARC’s Global Cancer Observatory (http://gco.iarc.fr). In
countries with longstanding cancer registries of high qual-
ity, an age-period-cohort analysis is warranted to determine
more explicitly the role of period effects (linked mainly to
artifact, such as changes in practices affecting all studied age
groups at a given time or time period) versus birth cohort
effects (linked mainly to changes in population-level risk
and the prevalence of the underlying determinants among
successive generations).
Conclusion
The marked differences in contemporary NHL incidence
rates by country and region may be partly linked to contrast-
ing levels of access to care and the availability of diagnostic
services. In addition, endemic infections and environmen-
tal exposures in regions in Africa, Asia, and Latin America
likely contribute to these differences. Changes in classifica-
tion of NHL have been applied at different time points in the
contributing registries, and these may have partially affected
the observed patterns and time trends. All of these factors
need to be taken into account to gain further insight into this
complex set of diseases.
Acknowledgments The work reported here was undertaken by Dr.
Miranda-Filho during the tenure of an IARC Postdoctoral Fellowship,
partially supported by the European Commission FP7 Marie Curie—
Actions—People—co-funding regional, national, and international
programmes (COFUND). We would like to thank the Directors and
staff of the population-based cancer registries worldwide who compiled
and submitted their data for the CI5 and GLOBOCAN projects used
in this paper.
Compliance with ethical standards
Conflict of interest The authors declare no competing interests.
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... (3) Studies have revealed that NHL cases were more likely to be diagnosed at older ages (4) among White people in the United States. (5) Moreover, chronic inflammation, (6) including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), (7) is a known risk factor for NHL overall, except for certain subtypes of NHL. In addition, family history of any cancer is one of the established risk factors for NHL. ...
... Notably, tea consumption was about 8.5 times higher in Asian compared to White; (27) whereas, higher risk and higher mortality rate of NHL were found among White populations, compared to Asian populations. (5) The difference in the occurrence of malignant lymphomas between different racial groups may be partly explained by tea-drinking habits. Additionally, previous findings indicate that tea protects against cigarette smoke-induced apoptosis. ...
... Potential confounders (4)(5)(6)(8)(9)(10) ...
Article
Although, biological evidence suggests that tea consumption may protect against non-Hodgkin lymphoma (NHL), epidemiologic evidence has been unclear. The aim of this study was to examine the association between tea-drinking habits and the risk of NHL in a large nationwide prospective cohort of postmenopausal US women. 68,854 women who were enrolled from 1993 through 1998 in the Women’s Health Initiative Observational Study (WHI-OS) and responded to year 3 annual follow-up questionnaire comprised the analytic cohort. Newly diagnosed NHL cases after the year 3 visit were confirmed by medical and pathology reports. Multivariable-adjusted Cox proportional hazards models were performed to assess the associations of tea-drinking habits (specifically, the amounts of caffeinated/herbal/decaffeinated tea intake) with the overall risk of NHL and 3 major subtypes (Diffuse large B-cell lymphoma, DLBCL, (n=195, 0.3%), follicular lymphoma, FL, (n=128, 0.2%), and chronic lymphocytic leukemia/small lymphocytic lymphoma, CLL/SLL, (n=51, 0.1%)). Among 62,622 participants, a total of 663 (1.1%) women developed NHL during a median follow-up of 16.51(SD±6.20) years. Overall, different amounts of type-specific tea intake were not associated with the risk of NHL regardless of its histologic subtypes after adjustment for confounders. Our findings suggest that tea intake at the current consumption level does not influence the risk of NHL, regardless of its histologic types.
... After a steady increase for several decades worldwide, in most parts of the World, incidence of non-Hodgkin's lymphoma (NHL) reached the top of the curve around the 1990's and stabilized thereafter [1]. According to the latest estimates from the 10 th Edition of the IARC Cancer Incidence in the Five Continents, across the 33 Italian Cancer Registries, NHL incidence ranges 9.7-17.4 ...
... Therefore, our results show that in 1974-2003 NHL incidence increased linearly among the population of the Italian region of Sardinia, in both the female and male population, and in all age groups. Cancer Registry data, partially available from the last decade of the 30-year time span covered by the oncohematology database we used, confirm its validity and completeness for the years 1998-2002 in northern Sardinia, and suggest no further increase in NHL incidence, consistently with what was observed in most countries worldwide [1]. Taking profit of the local, well-functioning Cancer Registry, another Italian study explored incidence of and survival from peripheral lymphomas, including Hodgkin's and non-Hodgkin's lymphomas and chronic lymphocytic leukemia (CLL), but not multiple myeloma (MM), over a relatively short time span [17]. ...
Article
The causes of the peculiar time trend in the incidence of non-Hodgkin's lymphoma (NHL) in most parts of the world and of its geographic distribution are still unknown. We used the data base of 1974-2003 incident cases of hematological malignancies to explore the time trend of NHL incidence in the region of Sardinia, Italy, and we used Bayesian methods to plot the probability of NHL incidence by residential unit on the regional map. In 1974-2003, 4109 NHL cases were diagnosed among resident adults in Sardinia, with an incidence rate of 13.38 x 10-5 (95% CI 12.97-13.80). NHL incidence showed an upward trend along the study period with an average annual percent change (APC) of 4.94 (95% CI -5.39-16.4), which did not vary by gender or by age-group. Cancer registry data, covering part of the region starting from 1993, suggest that the increasing trend did not persist in the subsequent years. Areas with the highest probability of an excess incidence tended to cluster in the north-eastern part of the region and in two major urban centers, with the low incidence areas located in the south, confirming previous observations. Prevalence of viral infections, environmental and occupational exposures, or socio-economic deprivation would not explain the peculiar geographic distribution we observed. These findings provide convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants of NHL in the risk areas.
... A pesar de una comprensión cada vez mayor de la patología y la genética de los linfomas, los informes globales sobre variaciones en la incidencia siguen siendo limitados en su número y alcance 37 . Las marcadas diferencias en las tasas de incidencia por país y región pueden estar relacionadas en parte con niveles contrastantes de acceso a la atención y la disponibilidad de servicios de diagnóstico. ...
Article
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Introducción: El cáncer representa un desafío para la salud pública global, ya que requiere de una estrategia integral para su control. En este contexto los Registros de Cáncer de Base Poblacional (RCBP) son actores clave para la generación de políticas públicas que garanticen su implementación. Objetivo: Este estudio analiza las tasas de incidencia y mortalidad por cáncer en la ciudad de Quito durante el período 1985-2017 y las discute en el marco de la Estrategia Nacional contra el cáncer propuesta en 2017 para Ecuador. Métodos: Se establecieron las tasas de incidencia y mortalidad estandarizadas por edad utilizando datos del RCBP de Quito. Para el análisis de las tendencias, de ubicaciones seleccionadas, se utilizó la regresión de join point y el cambio porcentual anual (CPA). Resultados: Durante todo el período de estudio, hubo un incremento sostenido tanto en las tasas de incidencia (CPA hombres= 2.0, IC 95%: 1.7-2.4; CPA mujeres= 2.0%, IC 95%: 1.4-2.6), como en las tasas de mortalidad (CPA hombres= 2.0%, IC 95%: 1.8-2.3; CPA mujeres= 1.3%, IC 95%: 1.1-1.6). La incidencia y mortalidad de los cánceres de mama, próstata, colon-recto, tiroides y linfoma se incrementaron, mientras que las tasas de incidencia de cáncer de cuello uterino y estómago disminuyeron inicialmente, luego se observó un estancamiento. Conclusión: La información presentada por el PBCR de Quito sirve como referencia para el pronóstico del cáncer en el país y como línea de base para su control. Son urgentes acciones para fortalecer las estrategias de prevención y promoción del cáncer.
... In a recent study on global epidemiology of lymphoma, the incidence and death rates due to NHL were lowest in Central Sub-Saharan Africa, South Asia, Central Asia, North Africa, and Middle East and highest in high-income North America, Australasia, and Western Europe, which could also explain the lower risk of lymphoma in our study. 26 Like our study, in a recent administrative database analysis from Japan, there was no difference in NHL incidence relative to general population in any treatment subgroup regardless of prescription of thiopurines. 27 However, a multicenter study from South Korea reported increased lymphoma risk in IBD patients in relation to thiopurine use, although the overall lymphoma risk in IBD patients was similar to general population. ...
Article
Background: Thiopurines are widely used to maintain remission in both Ulcerative Colitis (UC) and Crohn's Disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long-term efficacy and safety of thiopurines. Methods: Records of 5351 patients followed up at IBD clinic, All India institute of Medical Sciences, New Delhi from 2004-2020 were evaluated retrospectively. Safety was evaluated in terms of long-term adverse events and development of malignancy. Results: Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC=788 [proctitis-1.9%, left sided colitis-44.9%, pancolitis-53.1%], CD=305 [inflammatory-42.6%, stricturing-46.9%, fistulizing-10.5%]) were included (60.8%-males). Follow-up and treatment duration on thiopurine were 7(4-12) years and 39.4±40.3 months respectively with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred fifty-nine [UC:249(31.6%); CD:110(36.1%); p=0.1] patients developed adverse events (AE), commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥5 years) developed lymphoma or non-melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1,2 and 5 years was 78.6%, 71.9% and 68.4% respectively and this was comparable between UC and CD (p=0.09). Conclusion: Long-term follow up of patients with IBD from Northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non-melanoma skin cancer.
... Non-Hodgkin's lymphoma (NHL) has been identified as one of leading causes of cancer mortality [1,2]. The most common type of non-Hodgkin's lymphoma (NHL) is an aggressive tumor that affects B-lymphocytes; this is commonly known as diffuse large B-cell lymphoma (DLBCL), which accounts for approximately 30-40% of new cases of lymphoma [3]. ...
Article
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Background Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used to treat patients with diffuse large B-cell lymphoma (DLBCL) under National Health Insurance (NHI) scheme in Indonesia. This study aims to estimate its cost-effectiveness and budget impact. Methods We conducted a cost utility analysis using Markov model over a lifetime horizon, from a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital data. Direct non-medical costs, indirect costs, and utility data were primarily gathered by interviewing the patients. We applied 3% discount rate for both costs and effect. All monetary data are converted into USD (1 USD = IDR 14,000, 2019). Probabilistic sensitivity analysis was performed. In addition, from a payer perspective, budget impact analysis was estimated using price reduction scenarios. Results The incremental cost-effectiveness ratio (ICER) of R-CHOP was USD 4674/LYG and 9280/QALY. If we refer to the threshold three times the GDP per capita (USD 11,538), R-CHOP could thus be determined as a cost-effective therapy. Its significant health benefit has contributed to the considerable ICER result. Although the R-CHOP has been considered a cost-effective intervention, the financial consequence of R-CHOP if remain in benefit package under National Health Insurance (NHI) system in Indonesia is considerably substantial, approximately USD 35.00 million with 75% price reduction scenario. Conclusions As a favorable treatment for DLBCL, R-CHOP ensures value for money in Indonesia. Budget impact analysis provides results which can be used as further consideration for decision-makers in matters related to benefit packages.
... Les lymphomes non hodgkinien (LNH) sont des hémopathies malignes les plus courantes dans le monde [1]. Ils constituent un groupe hétérogène de tumeurs malignes qui se développe à partir de la transformation maligne de précurseurs cellulaires présents dans les organes lymphoïdes primaires et secondaires, affectant soit les lymphocytes B (environ 86% de tous les LNH), soit une petite proportion de lymphocytes T et de cellules Natural Killers (14 % de tous les LNH) à divers stades de différenciation [2][3][4]. Ce groupe, très diversifié en troubles lymphoprolifératifs, a un comportement biologique, histologique et clinique distinct avec des étiologies mal comprises [2,3,5]. Selon GLOBOCAN en 2020, le NLH a été responsable de 544000 nouveaux cas et 260000 décès (1) Available free at www.hsd-fmsb.org ...
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Introduction. Les lymphomes non-Hodgkiniens (LNH) sont des hémopathies développées à partir de précurseurs cellulaires présents dans les organes lymphoïdes et dont la pathogénèse implique la production de lymphocytes anormaux, ce qui pourrait affecter significativement les taux de Lymphocytes T CD4 + (LT CD4 +) au cours d'un LNH. L'objectif de cette étude était d'étudier la variation des quantités de LT CD4 + en fonction de quelques paramètres cliniques chez des sujets atteints de LNH. Méthodologie. Une étude transversale a été menée sur des malades présentant un LNH à l'Hôpital Général de Yaoundé d'Octobre 2018 à Mars 2019. Pour chaque patient consentant, du sang a été prélevé et les LT CD4 + quantifiés par immunophénotypage. Les variables étudiées au cours de l'étude étaient démographiques, cliniques et biologiques. Résultats. Quarante participants ont été enrôlés dans cette l'étude. L'âge moyen de la cohorte était de 51±16 ans, avec un sex ratio de 1,5. L'amaigrissement et l'état général altéré étaient les principales causes d'évolutivité clinique. La localisation ganglionnaire, le lymphome de type agressif et le stade avancé de la maladie, étaient les paramètres majoritaires au sein de notre population d'étude. Le nombre médian de LT CD4 + mesurés a été de 723 cellules/mm 3 et est resté élevé quel que soit le paramètre démographique et clinique utilisé. Conclusion. Bien que la lymphopénie reste un trait commun aux malades atteints de LNH selon la littérature, notre étude a montré un taux de LT CD4 + élevé chez ces malades. ABSTRACT Introduction. Non-Hodgkin's lymphomas (NHL) are hemopathies developed from cell precursors present in lymphoid organs and whose pathogenesis involves the production of abnormal lymphocytes, which could significantly affect CD4+ T-Lymphocyte levels (CD4+TL) during an NHL. Objective. To profile the CD4+TL variation rate, based on few clinical parameters in subjects with NHL. Methods. A cross-sectional study was conducted on NHL patients at Yaoundé General Hospital from October 2018 to March 2019. For each consenting patient, venous blood was collected and CD4+TL quantified by immunophenotyping. The studied characteristics were demographic, clinical and biological. Results. Forty participants were enrolled. Their average age was 51±16 years, with a sex ratio of 1.5. Weight loss and impaired overall condition were the main causes of clinical evolutivity. Lymph node location, aggressive lymphoma and advanced stage of disease were the most common clinical parameters in our population. The median number of LT CD4+ TL was 723 cells/mm3 and remained high regardless of the demographic and clinical endpoint used. Conclusion. Although lymphopenia remains a common trait in NHL patients according to the literature, our study showed a high CD4+ TL rate in these patients.
... This could be explained through the underrecording of cases in previous reports and/or the rising incidence rates of NMSC in the last decades (48). Furthermore, studies on CVID-associated cancers can be confounded by variations between patient cohorts and especially the regional variability in the prevalence of the diverse types of cancer (49,50). Evaluation of relative occurrence of different forms of cancer in CVID through the calculation of its prevalence can be biased, given the differences in the demographic parameters between studied cohorts and the general population. ...
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Objective The aim of this study was to investigate the prevalence of cancer and associating clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID).Methods In this retrospective monocenter cohort study, we estimated the standardized incidence ratio (SIR) for different forms of cancer diagnosed in CVID patients. Furthermore, we evaluated the likely association of infectious and non-infectious CVID-related phenotypes with the diagnosis of cancer by calculation of the odds ratio. The genetic background of CVID in patients with cancer was evaluated with sequential targeted next-generation sequencing (tNGS) and whole-exome sequencing (WES). Patients’ family history and WES data were evaluated for genetic predisposition to cancer.ResultsA total of 27/219 patients (12.3%) were diagnosed with at least one type of cancer. Most common types of cancer were gastric cancer (SIR: 16.5), non-melanoma skin cancer (NMSC) (SIR: 12.7), and non-Hodgkin lymphoma (NHL) (SIR: 12.2). Immune dysregulation manifesting as arthritis, atrophic gastritis, or interstitial lung disease (ILD) was associated with the diagnosis of cancer. Furthermore, diagnosis of NMSC associated with the diagnosis of an alternative type of cancer. Studied immunological parameters did not display any significant difference between patients with cancer and those without. tNGS and/or WES yielded a definite or likely genetic diagnosis in 11.1% of CVID patients with cancer. Based on identified variants in cancer-associated genes, the types of diagnosed cancers, and family history data, 14.3% of studied patients may have a likely genetic susceptibility to cancer, falling under a known hereditary cancer syndrome.Conclusions Gastric cancer, NMSC, and NHL are the most frequent CVID-associated types of cancer. Manifestations of immune dysregulation, such as arthritis and ILD, were identified as risk factors of malignancy in CVID, whereas studied immunological parameters or the identification of a monogenic form of CVID appears to have a limited role in the evaluation of cancer risk in CVID.
Article
Purpose: To describe the cancer incidence burden and trends among adolescent and young adults (AYAs) in Alberta, Canada over a 35-year period. Methods: We obtained data from the Alberta Cancer Registry on all first primary cancers, excluding non-melanoma skin cancer, diagnosed at ages 15-39 years among residents in Alberta from 1983 to 2017. Cancers were classified by using Barr's AYA cancer classification system. Age-standardized incidence rates (ASIR) and the average annual percentage change (AAPC) in incidence rates were calculated. Statistically significant changes in the AAPC during the study period were assessed using Joinpoint regression. Results: Overall, 23,652 incident cases of AYA cancer were diagnosed in Alberta. Females accounted for ∼60% of the diagnoses. AYA cancer increased significantly over the study period overall (AAPC: 0.5%; 95%CI: 0.3%-0.7%), for each sex (AAPCmale: 0.7%; 95%CI: 0.4%-0.9%; AAPCfemale: 0.4%; 95%CI: 0.2%-0.6%), and among male and female 20-39 year-olds. Although statistically significant increases were observed in 11 out of 29 cancer sites for at least a portion of the study period, with significant AAPCs ranging from 0.8% (95%CI: 0.01%-1.5%) to 6.6% (95%CI: 4.6%-8.5%), the main driver was thyroid cancer (AAPC: 3.7%; 95%CI: 3.2%-4.2%). Statistically significant decreases were observed for six cancer sites, with AAPCs ranging from -6.4% (95%CI: -8.7% to -4.1%) to -1.1% (95%CI: -1.8% to -0.5%). Conclusions: There is a growing cancer burden among AYAs in Alberta, which is driven primarily by thyroid cancer and early-onset cancers in males. These results highlight the need for etiological studies and tertiary strategies to prevent and mitigate morbidity and mortality in the AYA population.
Article
Selinexor is a first-in-class, oral therapy that selectively inhibits nuclear export. The drug is active with an overall response rate (ORR) of approximately 30% in relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL). Long-term patient follow-up has not been reported. Thirty-one NHL patients were treated between July 2012 and July 2018; 22 were evaluated for response. ORR was 32% (7/22). Two patients achieved complete remission (CR) and were alive and lymphoma-free at the end of follow-up. Fifteen patients (68%) progressed during treatment, most of them died within 3-10 months. The most common grade 3/4 adverse events were gastrointestinal and hematological. Median follow up was 50 months. Overall survival for the entire cohort was 16%. Selinexor monotherapy for r/r NHL is an active therapy with the potential for long-term disease control. It may serve as a 'bridge' to subsequent therapy. Additional studies are needed to identify predictive biomarkers and to evaluate combination approaches.
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Lymphoma refers to a group of cancers that arise from lymphocytes and is the most common form of hematological malignancy in adults. While the recent availability of specific chemotherapy regimes has resulted in good patient outcomes for some lymphoma subtypes, relapsed and refractory lymphoma is still a challenge that needs to be overcome. This review discusses how Nrf-2 regulated antioxidant systems such as the thioredoxin and glutathione systems are upregulated in lymphomas and have been linked with several signaling pathways involved in lymphoma development and progression, including the B cell receptor, the NF-κB, and the STAT3 signaling pathways. Thioredoxin reductase (TrxR) has been recognized as a potential anticancer target and, as a consequence, the synthesis of TrxR inhibitors, along with the discovery of inhibitors from natural resources and evaluation of their anti-cancer effects, is an ongoing active area of research. Targeting antioxidant systems, especially TrxR, may represent a new valid therapeutic approach for lymphoma, potentially in combination with existing therapies.
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Background: Infections with certain viruses, bacteria, and parasites are strong risk factors for specific cancers. As new cancer statistics and epidemiological findings have accumulated in the past 5 years, we aimed to assess the causal involvement of the main carcinogenic agents in different cancer types for the year 2012. Methods: We considered ten infectious agents classified as carcinogenic to human beings by the International Agency for Research on Cancer. We calculated the number of new cancer cases in 2012 attributable to infections by country, by combining cancer incidence estimates (from GLOBOCAN 2012) with estimates of attributable fraction (AF) for the infectious agents. AF estimates were calculated from the prevalence of infection in cancer cases and the relative risk for the infection (for some sites). Estimates of infection prevalence, relative risk, and corresponding 95% CIs for AF were obtained from systematic reviews and pooled analyses. Findings: Of 14 million new cancer cases in 2012, 2·2 million (15·4%) were attributable to carcinogenic infections. The most important infectious agents worldwide were Helicobacter pylori (770 000 cases), human papillomavirus (640 000), hepatitis B virus (420 000), hepatitis C virus (170 000), and Epstein-Barr virus (120 000). Kaposi's sarcoma was the second largest contributor to the cancer burden in sub-Saharan Africa. The AFs for infection varied by country and development status—from less than 5% in the USA, Canada, Australia, New Zealand, and some countries in western and northern Europe to more than 50% in some countries in sub-Saharan Africa. Interpretation: A large potential exists for reducing the burden of cancer caused by infections. Socioeconomic development is associated with a decrease in infection-associated cancers; however, to reduce the incidence of these cancers without delay, population-based vaccination and screen-and-treat programmes should be made accessible and available. Funding: Fondation de France.
Article
This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high‐quality cancer registry data, the basis for planning and implementing evidence‐based cancer control programs, are not available in most low‐ and middle‐income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1‐31. © 2018 American Cancer Society
Article
Background: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. Methods: CONCORD-3 includes individual records for 37·5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. Findings: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89·5% in Australia and 90·2% in the USA, but international differences remain very wide, with levels as low as 66·1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68·9%), colon (71·8%), and rectum (71·1%); in Japan for oesophageal cancer (36·0%); and in Taiwan for liver cancer (27·9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59·9% in South Korea, 52·1% in Taiwan, and 49·6% in China), and for both lymphoid malignancies (52·5%, 50·5%, and 38·3%) and myeloid malignancies (45·9%, 33·4%, and 24·8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49·8% in Ecuador to 95·2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28·9% in Brazil to nearly 80% in Sweden and Denmark). Interpretation: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. Funding: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation.
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Lymphomas can affect any organ in the body, present with a wide range of symptoms, and be seen by primary care physicians and physicians from most specialties. They are traditionally divided into Hodgkin's lymphoma (which accounts for about 10% of all lymphomas) and non-Hodgkin lymphoma, which is the topic of this Seminar. Non-Hodgkin lymphoma represents a wide spectrum of illnesses that vary from the most indolent to the most aggressive malignancies. They arise from lymphocytes that are at various stages of development, and the characteristics of the specific lymphoma subtype reflect those of the cell from which they originated. Since this topic was last reviewed in The Lancet in 2012, advances in understanding the biology and genetics of non-Hodgkin lymphoma and the availability of new diagnostic methods and therapies have improved our ability to manage patients with this disorder.
Article
Purpose of review: The purpose of this review is to describe the epidemiology of cancers that occur at an elevated rate among people with HIV infection in the current treatment era, including discussion of the cause of these cancers, as well as changes in cancer incidence and burden over time. Recent findings: Rates of Kaposi sarcoma, non-Hodgkin lymphoma and cervical cancer have declined sharply in developed countries during the highly active antiretroviral therapy era, but remain elevated 800-fold, 10-fold and four-fold, respectively, compared with the general population. Most studies have reported significant increases in liver cancer rates and decreases in lung cancer over time. Although some studies have reported significant increases in anal cancer rates and declines in Hodgkin lymphoma rates, others have shown stable incidence. Declining mortality among HIV-infected individuals has resulted in the growth and aging of the HIV-infected population, causing an increase in the number of non-AIDS-defining cancers diagnosed each year in HIV-infected people. Summary: The epidemiology of cancer among HIV-infected people has evolved since the beginning of the HIV epidemic with particularly marked changes since the introduction of modern treatment. Public health interventions aimed at prevention and early detection of cancer among HIV-infected people are needed.
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The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 27 centers in 25 countries using the World Health Organization classification and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males in the developing regions compared to the developed world (p<0.05). The median age at diagnosis was significantly lower for both low- and high-grade B-cell lymphoma in the developing regions. The developing regions had a significantly lower frequency of B-cell lymphoma (86.6%) and a higher frequency of T- and NK-cell lymphoma (13.4%) compared to the developed world (90.7% and 9.3%, respectively). Also, the developing regions had significantly more cases of high-grade B-cell lymphoma (59.6%) and fewer cases of low-grade B-cell lymphoma (22.7%) compared to the developed world (39.2% and 32.7%, respectively). Among the B-cell lymphomas, diffuse large B-cell lymphoma was the most common subtype (42.5%) in the developing regions. Burkitt lymphoma (2.2%), precursor B- and T-lymphoblastic leukemia/lymphoma (1.1% and 2.9%) and extranodal NK/T-cell lymphoma (2.2%) were also significantly increased in the developing regions. These findings suggest that differences in etiologic and host risk factors are likely responsible and more detailed epidemiologic studies are needed to better understand these differences.
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Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV-positive DLBCL can be seen in younger, immunocompetent patients. The diagnosis of EBV-positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The International Prognostic Index (IPI), and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor. Patients with EBV-positive DLBCL should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. It has been suggested, however, that EBV-positive patients have a worse prognosis than EBV-negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV-positive DLBCL.