2099
Acute Myeloid Leukemia: Epidemiology and Etiology
Barbara Deschler, MD
Michael Lübbert, MD, PhD
Department of Hematology/Oncology, University
of Freiburg, Freiburg, Germany.
Address for reprints: Barbara Deschler, MD,
Department of Hematology/Oncology, University
of Freiburg, Hugstetterstr. 55, D-79106 Freiburg,
Germany; Fax: (011) 49 761-270-3690; E-mail:
deschler@mm11.ukl.uni-freiburg.de
Received July 7, 2006; revision received July 31,
2006; accepted August 3, 2006.
ª 2006 American Cancer Society
DOI 10.1002/cncr.22233
Published online 3 October 2006 in Wiley InterScience (www.interscience.wiley.com).
Acute myeloid leukemias (AMLs) are infrequent, yet highly malignant neoplasms
responsible for a large number of cancer-related deaths. The incidence has been
near stable over the last years. It continuously shows 2 peaks in occurrence in
early childhood and later adulthood. With an incidence of 3.7 per 100,000 per-
sons and an age-dependent mortality of 2.7 to nearly 18 per 100,000 persons,
there is a rising awareness in the Western world of AML’s special attributes result-
ing from an ever-aging population. To objectively describe epidemiologic data on
this patient population, recent publications were evaluated to make transparent
the current trends and facts. A review of the literature is presented, reflecting
highlights of current research with respect to AML etiology. To estimate outcome
and discuss informed treatment decisions with AML patients of different age
groups and different biologic risk categories, it is mandatory to consider that the
outcome results reported in clinical trials were until now heavily biased toward
younger patients, whereas the overall dismal prognosis documented in popula-
tion-based studies most likely reflects the exclusion of older patients from aggres-
sive treatment. The etiology for most cases of AML is unclear, but a growing
knowledge concerning leukemogenenic agents within chemotherapy regimens for
other malignancies is already available. This includes specific associations of the
most frequent balanced translocations in AML, including the ‘‘good-risk’’ abnormal-
ities comprised by the core binding factor leukemias (i.e., AML with the translocation
(8;21) and inversion of chromosome 16, and acute promyelocytic leukemia with the
translocation (15;17)). In contrast to these genetic alterations, epigenetic lesions,
e.g., promoter silencing by hypermethylation of the p15/INK4b and other genes,
are increasingly recognized as important in the pathogenesis of AML. Cancer
2006;107:2099–107.
2006 American Cancer Society.
KEYWORDS: acute myeloid leukemia, epidemiology, etiology, survival.
A cute leukemias are rare diseases, but have a disproportionally
large effect on cancer survival statistics.1 Acute myeloid leuke-
mia (AML) is the most common type of leukemia in adults, yet con-
tinues to have the lowest survival rate of all leukemias. Although
rates have improved remarkably in the younger age group, the prog-
nosis in older patients continues to be very poor.2,3
Incidence
The American Cancer Society estimates that 31,500 individuals in
the U.S. will be diagnosed with 1 form of leukemia annually.
Approximately 21,500 patients will die of their disease.4,5 Although
the incidence of acute leukemias accounts for <3% of all cancers,
these diseases constitute the leading cause of death due to cancer
in children and persons age <39 years.4–6
AML accounts for approximately 25% of all leukemias in adults
in the Western world, and therefore is the most frequent form of
2100 CANCER November 1, 2006 / Volume 107 / Number 9
FIGURE 1. Age-specific incidence of acute myeloid leukemia in the U.S.,
20002003. Source: Surveillance, Epidemiology, and End Results program.
leukemia.4,7 Worldwide, the incidence of AML is
highest in the U.S., Australia, and western Europe.8
The age-adjusted incidence rate of AML in the U.S.
in the years 1975–2003 was approximately 3.4 per
100,000 persons (¼2.5 per 100,000 persons when
age-adjusted to the world standard population).9 The
American Cancer Society estimates that 11,930 men
and women (6350 men and 5580 women) in the U.S.
will be diagnosed with AML in 2006.10
Age
Leukemia is the most common cancer diagnosis in
children age <15 years, with an overall incidence of
4.3 per 100,000 persons in the U.S.9 However, in this
age group acute lymphocytic leukemia (ALL) is ap-
proximately 5 times more common than AML,
thereby accounting for approximately 76% of all
childhood leukemia diagnoses. Conversely, AML
comprises only 15% to 20% of cases in patients age

15 years.11 The peak incidence rate occurs in the
first year of life and then decreases steadily up to the
age of 4 years, at which point it remains relatively
constant throughout the years of childhood and early
adulthood.12
AML is therefore primarily a disease of later
adulthood. The distribution of the proportion of pre-
valent cases of all leukemias in the U.K. shows that
42.8% of patients are age >65 years. Patients newly
diagnosed with AML have a median age of 65
years.13 AML is rarely diagnosed before the age of 40
years; thereafter, the incidence increases progres-
sively with age. From 2000 to 2003, the U.S. inci-
dence rate in people age <65 years was only 1.8 per
100,000 persons, whereas the incidence rate in
people age  65 years was 17 per 100,000 persons
(Fig. 1).9 As shown in Figure 1, a slight decrease in
the incidence of AML in patients age >85 years in
the U.S. population raises the question of whether a
lack of published data regarding this phenomenon
presents an artifact due to underdiagnosed AML
cases in the oldest old.
Based on the documented frequent progression
of myelodysplastic syndromes (MDS) to AML, an
increased incidence of MDS with age appears to
partly explain both the high incidence and poor
prognosis of AML in the elderly. Because an increas-
ing blast count in MDS leads to higher mortality
without reaching the definition of AML, a distinction
between the 2 entities of myeloid disorders may be
primarily semantic. The common AML subtype in
the elderly shares characteristics with AML that fol-
lows MDS, Fanconi anemia, and alkylating agent
chemotherapy, and occurs in an estimated 10% to
15% of AML in younger patients. It has been referred
to as MDS-related AML and is characterized by com-
mon cytogenetic abnormalities shared with MDS,
and frequent multilineage dysplastic morphology in
residual hematopoietic precursors. By contrast, AML
with genotypes typical of younger patients, true de
novo AML, has an approximately flat incidence
throughout life, also in progressive age groups.
Approximately 5% of elderly patients with AML are
estimated to belong to the true de novo AML group,
which is consistent with the incidence in younger
patients.14
An increased incidence of unfavorable cytogenet-
ics contributes to poor outcome in patients age >56
years, and, within each cytogenetic risk group, treat-
ment outcome deteriorates with age.15,16
Although incidence rates for AML have been
reported to be nearly stable over time among the dif-
ferent age groups, there was a slight increase noted
among the oldest group.17
Gender and Ethnicity
The incidence of AML varies with gender and race.
In the Surveillance, Epidemiology, and End Result
(SEER) database for children ages 1 to 4 years there
was an incidence rate of 0.8 per 100,000 persons for
boys and for girls. In the first few years of life, the
incidence of AML in whites is 3-fold higher than in
blacks; however, blacks have slightly higher rates of
AML among children age 3 years.12
AML in adults has a slight male predominance
in most countries. In 2000–2003, the age-adjusted
incidence rate of AML in the U.S. was 3.7 per
100,000 for both sexes, 4.6 per 100,000 for males, and
3.0 per 100,000 for females. The incidence rate of
U.S. males is substantially higher than the incidence
rates reported for males in all other countries.18
In the U.S. in 2000, AML was more common in
blacks than in whites. However, during 2000 to 2003,
the incidence of AML for blacks (3.2 per 100,000 per-
sons) was lower than for whites (3.8 per 100,000 per-
sons).9
 Epidemiology and Etiology of AML/Deschler and Lübbert
Mortality
Untreated AML is a uniformly fatal disease. Although
it is possible to support patients for a certain period
(median survival, 11–20 weeks),19,20 they ultimately
die of the leading complications associated with
bone marrow failure (i.e., infection and hemorrhage).
Most patients seek medical attention for symptoms
related to anemia, infection, or bleeding, and those
patients typically require immediate therapeutic in-
tervention. Other patients are not candidates for cy-
totoxic therapy, mainly because of older age and/or
poor performance status or other active severe medi-
cal comorbidities that complicate their care. In such
settings, a supportive strategy may be most appropri-
ate.21 Firm stratification criteria for decision-making
in this setting are not uniformly established.
After long-term increases or mostly level trends
that date from the 1930s, death rates for all leuke-
mias were reportedly decreasing in the 1990s in the
U.S. and Europe.6,22 From 2000 to 2003, the U.S. age-
adjusted mortality rate of AML was 2.7 per 100,000
persons. As is the case with incidence, the mortality
associated with AML varies with age, gender, and
race. Mortality rates in the U.S. appear to increase
with age because the age-adjusted mortality rate
shows its peak at 17.6 per 100,000 persons in people
ages 80 to 84 years.
The mortality rate for males is higher than that
for females, with the U.S. age-adjusted mortality rate
at 3.5 per 100,000 for males and 2.2 per 100,000 for
females (2000–2003). AML mortality is greater in
whites than in blacks. The U.S. age-adjusted mortal-
ity rate was 2.7 per 100,000 for whites and 2.2 per
100,000 for blacks in the year 2000. It is estimated
that approximately 7,800 adults will die annually of
AML in the U.S.7,10,23
Early Survivorship
A comprehensive report on the total leukemia inci-
dence and survival in the U.S. covered the period
1973 to 1990.24 Here, overall survival rates for all leu-
kemia patients improved only slightly when compar-
ing the periods 1974 to 1976 and 1983 to 1989, but
were consistently higher in whites compared with
blacks, with little gender difference noted. When ana-
lyzing survival rates in more detail, it was found that
in comparing the period 1974 to 1983 with 1984 to
1993, overall survival rates improved notably among
all races/age groups age <45 years. However, for
blacks age 45 years there was little improvement in
overall survival. In particular, for blacks age >65
years, survival rates for leukemia were decreasing,
which was not observed in earlier data.17 To our
knowledge, the reasons for these gender and racial
2101
FIGURE 2. Age associated with 5-year relative survival in patients with
acute myeloid leukemia in the U.S., 19962002. Source: Surveillance, Epi-
demiology, and End Results program.
differences observed in all subtypes of leukemia
remain unclear.
The overall U.S. survival rate associated with
AML from 1996 to 2002 was 21.7%.10 Figure 2 depicts
5-year survival rates stratified by age. The 5-year
relative survival rate was highest for those who were
younger and female. In AML, however, as opposed to
the entire group of leukemias, blacks had a slightly
better 5-year survival rate than whites (21.5% vs.
19.8%).
A recent study reported that the 5-year survival
rate of those age
55 years was 23%, whereas the
corresponding rate for those age >55 years was 11%.
Survival rates have increased in the last decade
among this younger group (from 9% in the 1980s to
35% in the 1990s), but have not changed in the older
group, who therefore pose the biggest challenge for
achieving a therapeutic success.9
In a large recent Italian population-based study
(n ¼ 1005), the median survival of patients age >60
years with AML who were treated with either sup-
portive or aggressive therapy was 5 months and 7
months, respectively. In patients age >70 years, the
median survival was 4 months, which was, notably,
regardless of the type of therapeutic effort.20 Age has
further been shown to be inversely associated with 1)
referral to a treatment center25 and/or inclusion into
a clinical trial26; 2) tolerance to induction treatment
(early death or death during the immediate postche-
motherapy phase)27; and 3) the ability to achieve
remission. In older patients (age >60 years), standard
induction therapy achieves complete remission in
only 30% to 50% of treated individuals.28
Most rates of disease-free survival reported in
major clinical studies are above these rates (e.g., 4-year
survival rates of up to 42%),29 yet they too demon-
strate quite variable results. The differences in survival
results noted among various trials using similar chem-
otherapy can possibly be explained by the prevalence
of negative prognostic characteristics within a study
2102 CANCER November 1, 2006 / Volume 107 / Number 9
TABLE 1
Selected Population-Based Studies of Myeloid Neoplasias in Various
Populations: Survival Regardless of Treatment Strategy
Median age, Median survival,
Population years weeks Reference
Northern Sweden 63 7 25
Northern England 71 8 89
Italy 69 28 20
population.30 To understand clinical features and out-
comes of that significant number of patients not meet-
ing inclusion criteria for clinical studies, population-
based evaluations have found increasing attention.
Some results concerning age distribution, treatment
decisions, remission rates, and survival in AML do
demonstrate significant differences in some of the
large clinical investigations. In 1 report, of a total of
170 AML patients, 55% were treated outside a study
protocol.26 Nonstudy patients differed significantly
from patients included in clinical trials with respect to
age and performance status at the time of clinical pre-
sentation, comorbidity, and type of AML. Patients who
participated in a clinical trial had a median age of 46
years (range, 16–73 years), whereas those not included
were significantly older (median age of 63 years; range,
21–83 years). Survival was significantly better in
patients treated in a clinical protocol (median overall
survival of 15 months vs. 3.4 months). For survival
results in population-based studies, see Table 1. An
increase in median survival may possibly, at least
partly, be explained by improved supportive care over
the past decades.
Late Survivorship
The incidence of and risk factors for the develop-
ment of late sequelae of treatment in patients who
survived for >10 years (median, 15 years) after a di-
agnosis of childhood AML was evaluated at St. Jude
Children’s Research Hospital.31 Growth abnormalities
were the most common late effects in adulthood
(51%). Depending on the treatment modality (chem-
otherapy only, combined chemoradiotherapy, or com-
bined chemoradiotherapy with consecutive bone
marrow transplantation), endocrine abnormalities,
cataracts, cardiac abnormalities, academic difficul-
ties, and secondary malignancies resulted in 14% to
51% of cases. In addition to physical late effects, psy-
chosocial complications were observed. Some treat-
ment modalities are more likely than others to
produce certain long-term complications: Radiation
more frequently than chemotherapy results in growth
and neuroendocrine abnormalities and developmen-
TABLE 2
Selected Risk Factors Associated With Acute Myeloid Leukemia
Genetic disorders Down syndrome
Klinefelter syndrome
Patau syndrome
Ataxia telangiectasia
Shwachman syndrome
Kostman syndrome
Neurofibromatosis
Fanconi anemia
Li-Fraumeni syndrome
Physical and chemical exposures Benzene
Drugs such as pipobroman
Pesticides
Cigarette smoking
Embalming fluids
Herbicides
Radiation exposure Nontherapeutic, therapeutic
radiation
Chemotherapy Alkylating agents
Topoisomerase-II inhibitors
Anthracyclines
Taxanes
tal delay32; total body irradiation, for example, preced-
ing allogeneic bone marrow transplantation has been
shown to significantly impair growth in children33;
and corticosteroids and immobilization are suspected
to lead to osteopenia and osteoporosis.34 Frequently
occurring cardiovascular disease in survivors of AML
may be due in part to the administration of cardio-
toxic medication, but also to posttreatment obesity.32
Patients that survive AML and treatment have also
been monitored in a long-term follow-up at the Uni-
versity of Texas M. D. Anderson Cancer Center.35 Some
very relevant conclusions have been drawn in this
report. Only 10% of all 1892 patients entered the
potentially cured cohort, which was defined as the
patient population in complete remission after a fol-
low-up of 3 years. Those patients in the potentially
cured cohort were likely to be able to return to work,
suggesting that the major threat to patients with newly
diagnosed AML is the disease and not the treatment.
Etiology
The development of AML has been associated with
several risk factors, as summarized in Table 2. Gener-
ally, known risk factors account for only a small
number of observed cases.36 These include age, ante-
cedent hematologic disease, and genetic disorders; as
well as exposures to viruses as well as radiation,
chemical, or other occupational hazards and previ-
ous chemotherapy.11,37,38
Leukemogenesis is a multistep process that re-
quires the susceptibility of a hematopoietic progenitor
 Epidemiology and Etiology of AML/Deschler and Lübbert
cell to inductive agents at multiple stages. The differ-
ent subtypes of AML may have distinct causal me-
chanisms, suggesting a functional link between a
particular molecular abnormality or mutation and the
causal agent.39 Most cases of AML arise de novo with-
out objectifiable leukemogenic exposure.
Genetics
Genetic factors
Among children, genetic disorders and constitutional
genetic defects are important risk factors associated
with AML (Table 1).38 Children with Down syndrome
have a 10-fold to 20-fold increased likelihood of devel-
oping acute leukemia.40 Other inherited diseases asso-
ciated with AML include Klinefelter syndrome, Li-
Fraumeni syndrome,41 Fanconi anemia, and neurofi-
bromatosis.11 A recent study found that other risk fac-
tors for developing AML in children include race/
ethnicity, the father’s age at time of conception, and
time since the mother’s last live birth.42 Specifically,
Asian/Pacific Islander children had a higher risk than
non-Hispanic white infants; children born to fathers
age >35 years, compared with those ages 20 to 34
years, also were found to have an increased risk; and a
longer time since the last live birth (at least 7 years)
resulted in an elevated risk of children developing AML.
In this context, acute promyelocytic leukemia
(APL) has been investigated in detail. Representing
an example of a unique AML subtype (FAB M3) with
a characteristic morphology associated with distinct
chromosomal and gene rearrangement aberrations, it
has been shown to also have distinct epidemiologic
features. For yet unknown reasons, an increased inci-
dence of APL has been recognized in adult patients
originating in Latin America and in Southern Europe.
Of interest, the APL-specific gene rearrangement is
different in Latinos, with the majority of breakpoints
in the RARa gene in the PML/RARa transcript in
intron 6 (called bcr1). It therefore is speculated that
this particular breakpoint site may be determined ge-
netically.43–45
Acquired genetic abnormalities
Acquired (‘‘somatic’’) clonal chromosomal abnormal-
ities are found in 50% to 80% of AML cases,25,46–49
with rising incidences in patients with secondary leu-
kemia50 or older age.14,51–53
Frequently found abnormalities include loss or
deletion of chromosome 5, 7, Y, and 9, translocations
such as t(8;21)(q22;q22); t(15;17)(q22;q11), trisomy 8
and 21, and other abnormalities involving chromo-
somes 16, 9, and 11.
Multiple studies have demonstrated the prognos-
tic importance of cytogenetic abnormalities in AML,
2103
making this at present the most important predictor
of short-term30,54,55 and long-term35 outcome: Pa-
tients with a good prognosis are those with func-
tional inactivation of the core binding factors (CBFs):
AML1 and CBFb. These cases include patients with
AML and t(8;21)(q22;q22) or inv(16)(p13;q22), 2 of
the most frequent recurrent cytogenetic abnormal-
ities in de novo AML in younger patients.56
Poor-risk patients have a loss of all or part of
chromosome 5 or 7, translocations involving 11q23,
or abnormalities of chromosome 3.57
A model of a ‘‘2-hit-hypothesis’’ for the AML phe-
notype by so-called Class 1 and 2 mutations has been
suggested. It describes the cooperativity of activating
mutations in FLT3 (Fms-like tyrosine kinase 3)
(¼Class 1) and gene rearrangements involving hema-
topoietic transcription factors (¼Class 2). The ex-
pression of both classes may result in the AML
phenotype. FLT3 mutations have been associated with
all subtypes of AML, and with the majority of known
chromosomal translocations associated with AML. In
this hypothesis, FLT3 mutations serve as exemplary of
Class 1 mutations that, alone, confer a proliferative
and survival advantage to hematopoietic progenitors
but do not affect cell differentiation. Further examples
of Class 1 mutations are activating mutations in N-
RAS or K-RAS in AML. In contrast, Class 2 mutations
would be exemplified by AML1/ETO, CBFb/SMMHC,
PML/RARa, and MLL-related fusion genes. They
appear to impair hematopoietic differentiation, but
are not sufficient to cause leukemia when expressed
alone. This new hypothesis may have important im-
plications for novel treatment approaches (e.g., molec-
ular targeting of both FLT-3 and fusion proteins).58
Data have been published recently showing that
individuals with certain polymorphisms in genes
metabolizing carcinogens have an increased risk of
developing AML.59 NAD(P)H:quinone oxidoreductase
1 (NQO1), for example, is a carcinogen-metabolizing
enzyme that detoxifies quinones and reduces oxida-
tive stress. A polymorphism at nucleotide 609 of the
NQO1 complementary DNA results in a lowering of
the enzymes’ activity. This polymorphic variant is
associated with a predisposition to therapy-related
AML60 and selected cytogenetic subgroups of de
novo AML.61
Physical and Chemical Factors
A vast variety of environmental and chemical expo-
sures are assumed to be associated with a variably
elevated risk of developing AML in adults. Only a
limited number of hazards will be mentioned here.
Exposure to ionizing radiation is linked to AML.62
Among survivors of the atomic bomb explosions in
2104 CANCER November 1, 2006 / Volume 107 / Number 9
Japan, an increased incidence of AML was observed,
with a peak at 5 to 7 years after exposure. Also, thera-
peutic radiation has been found to increase the risk of
secondary AML.63
Chemotherapeutic agents, such as alkylating
agents and topoisomerase II inhibitors, have been re-
ported to increase the incidence of AML.64,65 A number
of other substances (therapeutic66 and occupational11)
have been linked to an increased risk of AML. Chronic
exposure to certain chemicals clearly shows an in-
creased risk for the development of AML. Benzene is
the best studied and most widely used potentially leu-
kemogenic agent.67 Persons exposed to embalming
fluids, ethylene oxides, and herbicides also appear to
be at increased risk. Furthermore, smoking has been
discussed to be associated with an increased risk of
developing AML (particularly of FAB subtype M2),
especially in those persons aged 60–75.37
Viruses
Viruses, particularly RNA retroviruses, have been found
to cause many neoplasms in experimental animals,
including leukemia.68 However, to our knowledge, a
clear retroviral cause for acute myeloid leukemia in
humans has not been identified to date. An association
between the exposure to certain viruses and the devel-
opment of AML has been suggested. Parvovirus B19
therefore could play a role in the pathogenesis of
AML.69 To our knowlege, however, it has so far not been
demonstrated that simple infection with either an
RNA- or DNA-based virus alone is a cause of acute my-
eloid leukemia.
Secondary AML
For most patients with acute leukemia, the cause of
the disease is unknown. ‘‘The true secondary AML’’
has been recommended to refer to patients who have
a clinical history of prior myelodysplastic syndrome
(MDS), myeloproliferative disorder, or exposure to
potentially leukemogenic therapies or agents; it is
thus a rather broad category.56 Greater than 90% of
secondary leukemias are of myeloid origin and have
a particularly poor outcome, with a lower incidence
of patients achieving a complete remission and a
shorter duration of survival than for patients with de
novo AML.70–72
Treatment-related secondary leukemia was first
observed in survivors of successfully treated Hodgkin
disease,73 which extended later to include survivors
of ALL74 and other disease entities such as multiple
myeloma.75
The development of secondary AML peaks in the
5 to 10 years after therapy. The distinct pattern of
cytogenetic and genetic abnormalities in secondary
or treatment-related AML is quite remarkable.76 It is
a subset of 10% to 20% of patients with AML in
whom the disease arises after previous therapy for
other malignancies. The risk of therapy-related AML
after intensive chemotherapy often is increased 100
times or more.77
Specific cytogenetic abnormalities currently serve
as the most important factor in distinguishing differ-
ences in AML biology, response to treatment, and
prognosis.49 The different abnormalities result in gene
rearrangements that may reflect the etiology and
pathogenesis of the disease.78 Treatment-related or
secondary leukemias are examples in which genetic
aberrations provide information regarding its specific
etiology. In understanding the mechanisms associated
with the development of secondary AML, general facts
concerning leukemia etiology can been elucidated.
In this context, genetic pathways with different eti-
ology and biologic characteristics have been proposed
for cytogenetic changes that can be related to previous
exposure to different chemically well-defined cytostatic
agents with a known mechanism of action.79 Among
those are alkylating agents: deletions or loss of 7q or
monosomy 7 with normal chromosome 564,80,81 and
deletions or loss of 5q or monosomy 5.82 For epipodo-
phyllotoxins, balanced translocations to chromosome
bands 11q23, primarily in children, have been de-
scribed.74 Topoisomerase II inhibitors have been linked
to t(8;21), inv(16).83 Topoisomerase II inhibitors, an-
thracyclines, and mitoxantrone,84 as well as radio-
therapy,85 may be associated with therapy-related acute
promyelocytic leukemia with t(15;17) and chimeric
rearrangements between PML and RARA genes as well
as different translocations to chromosome bands 11q15
and chimeric rearrangement between the NUP98 gene
and its partner genes.86 Another subgroup includes
10% to 15% of all patients with secondary AML, with
normal karyotype or various chromosome aberrations
uncharacteristic of t-AML.79
In the future, many more—as yet unknown genetic
and epigenetic changes—may be discovered. To our
knowledge to date, methylation of the promoter of
p15/IN4b, retinoic acid receptor (RAR)b2, SOCS-1 and
other genes are frequent abnormalities observed in a
high percentage of patients with AML,87 especially in
patients with secondary AML.88
The observed changes may pose an option for
future attempts to decipher epidemiologic and etiologic
findings as well as accelerate the development of new
treatment strategies.
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