South African Institute for Medical Research and
University of the Witwatersrand. Address for correspondence:
Department of Haematology, SAIMR, Baragwanath Hospital, PO Bertsham,
Soweto 2013, South Africa.
Until recently, cALL has been uncommon in sub-Saharan Africa, but
there is now emerging a peak of incidence at the age 3 to 5 years
in west and southern Africa. Prognosis for African patients with
cALL is poor because of a multitude of clinical, biological and
social factors. AML is seen at high frequency (probably indicating
truly high incidence) in male children 5 .14 years, of whom up to
a quarter present with chloroma. It is predicted that the incidence
of AML in adults may rise in the near future, related to cigarette
smoking, occupational and environmental exposures to benzene and
other pollutants, and the prescription of alkylating agents to young
people with malignant disease. CML shows no particular epidemiological
features, except for a high frequency in young adults and children,
reflecting the age structure of the whole population. There are
two forms of B.CLL: one is seen most commonly in women of low socioeconomic
status towards the end of their reproductive life, and is probably
related to an initially polyclonal expansion of B.cells in response
of recurrent malaria and other infections; the other is seen over
the age of 45 years, with men being affected twice as commonly as
women, as in the western world. The study of epidemiology of leukaemias
in Africa has been held back by the lack of accurate population
census figures, the shortage of haematologIsts and the under-development
of laboratories. Therapy is almost always grossly inadequate because
of limited supplies of pharmaceuticals, the absence of radIotherapy
except in a few centres, and the inability or unwillingness of patients
to continue treatment regimes for long periods of time. Despite
these handicaps, a large corpus of knowledge has been acquired:
this is of global interest, especially in the questions it roses
as to epidemIology and possible aetiologies ( 1 ).
ACUTE LYMPHOBLASTIC LEUKAEMIAS
There are three epidemiology patterns of incidence of ALL in the
world (Table 1) (2). The distinction between epidemiological patterns
I and II is certainly wholly false, and is the result of a low rate
of diagnosis. Patients with ALL are likely to be dying early of
intercurrent infections; they may not attend the hospitals because
of a lack of trust, long distances to travel and costs. When patients
do attend, the diagnosis may not be entertained in a paediatric
clinic where patients commonly present with fever, infection, lymphadenopathy
and splenomegaly from other causes. If a peripheral blood film IS
examined, the blast cells are likely to be mistaken for activated
lymphocytes seen in almost all sick children where malaria is endemic.
When the diagnosis is made, there is often no routine for recording
and registration of cases. Development of haematology services led
to pattern II being reported in Uganda in 1951 (3), in Nigeria 10
years later (4), but not ( disgracefully for the richest sub-Saharan
country) in the black population of South Africa until 1975 (5).
Where there are experienced haematologists who invest their skills
into the diagnosis of ALL in sub-Saharan Africa, the rate of diagnosis
Table 1. Epidemiological patterns of acute
remains lower than in western countries. The male to female ratio
is about 2: 1, there is a low frequency below 5 years of age, but
a peak at 5 to 14 years (Table 1) (2). The majority o leukaemias
are L2 on the French American British (F AB) classification and
phenotypically T -ALL, while c-ALL is a rarity (2, 6, 7). T-ALL
is relatively more common, but probably does not have a higher incidence
than in the rest of the world. There has been a perceptible increase
in the frequency of diagnosis of cALL in black children during the
past five years in Nigeria, South Africa and Zimbabwe, with an emerging
peak at 3 to 4 years of age, although there is a tendency for relatively
more black than white children to present between 5 and 10 years
of age (8-10). This emergence of a distinctive age peak of cALL
in early childhood in urban Africa may be associated causatively
with a general improvement of living standards, and follows ItS
emer~ence in the United Kingdom in the 1920s, in Whites m the United
States and Australasia in the 1940s, in Whites in South Africa in
the 1950s, in black US children in the 1960s, in Japan and Malaysia
in the 1970s, and in Saudi Arabia in the 1980s (1, 2, 11,12).
It may be hypothesized that there is a putative childhood leukaemia
virus, which is ubiquitous in communities with low levels of hygiene,
commonly infects young children causing no or trivial symptoms and
is followed by acquired immunity (13): with improving living standards
and better hygiene, the mean age of first exposure rises and women
experience their primary infections with increasing frequency during
pregnancy (14): transplacental transmissIon of the putative childhood
leukaemia virus from a non-immune mother to her infant is one step
towards the development of cALL (13): within communities with high
levels of hygiene, infection during pregnancy and cALL in childhood
is more common in first pregnancies, in those of high socioeconomic
status (15), in those living in remote areas (16) and following
mixing of populations (17, 18). Children of Asian and west Indian
ethnic origins living in the United Kingdom have similar patterns
of incidence of ALL to white Causasians, an observation which supports
the view that environmental factors are more important than genetic
Black African children demonstrate a whole constellation of clinical,
biological and sociological features associated with poor prognosis,
both in low complete remission rates and short survival (1). Common
indicators of poor prognosis include older age, male sex, high initial
leucocyte counts, late presentation with central nervous system
involvement, mediastinal masses, L2 or L3 blasts, and T -cell phenotype
(20). In tropical Africa, all hospital facilities, cytotoxic therapies
and radiotherapy are usually substandard or absent (21). Where facilities
are adequate compliance is often poor for a variety of reasons,
including lack of communication between health professionals and
patients, mistrust, long distances to hospital and high costs (22).
Multivariant analysis demonstrated that these factors did not totally
account for poor prognosis in black Americans, and that there could
be some additional undefined host-factors, possible genetically
determined (20). In Johannesburg, South Africa, it has been shown
that black males with cALL, had the lowest CD10 antigen density,
as well as having the worst prognosis: white females had the highest
CD10 antigen density and the best prognosis, while the black females
and white males occupied intermediate positions: it was hypothesized
that the low density CD10 pattern in males and Blacks could be agenetic
marker of poor prognosis (23). Regrettably it may be said that patients
with ALL in tropical Africa have benefited little or not at all
from the great advances which have been made in management during
the past decades.
ACUTE MYELOID LEUKAEMIAS
AML is diagnosed at equal frequency as ALL in childhood in sub-Saharan
Africa, in contrast to the western world where childhood ALL is
seen about four times as often as AML (1,2). The difference in relative
rates is due in part to the low incidence of cALL in African children,
but also it seems that there is a high incidence of AML; the male
to female ratio can approach 4:1, and AML is especially common in
boys age 5 to 14 years (Table 2) (24). Between 10% and 25% of children,
usually males, have chloromas, most commonly arising in the orbit,
in east, west and southern Africa, but this presentation
Table 2 Acute leukaemias in children and
adults in northern Nigeria (24).
is rare in north Africa (1, 2, 10, 25). AML is seen at any age amongst
adults and at about equal gender incidence (Table 2). All FAD types
occur, but M3 and M4 are reported to be predominant in Zimbabwe
(10). There appears to be a dual distribution of AML in Africa:
one pattern affects children of low socioeconomic status, especially
boys who often present with chloromas; the other pattern is seen
in adults of both genders and is not related to socioeconomic status
(2, 26). Exposure to chemicals, toxic waste and radioactivity at
work and in the environment is increasing and is largely uncontrolled
in sub-Saharan Africa. Recognized risks for AML are exposure to
benzene, pesticides and herbicides (27). Unofficial vendors of petroleum
and workers in small mechanical workshops have high though unmeasured
exposure to benzene, and in northern Nigeria have been shown to
be frequently anaemic, leucopenic and thrombocytopenic, and may
be assumed to be at risk for AML (2, 28). Cigarette smoke is probably
the main source of individual exposure to benzene, represents the
commonest identifiable cause of AML, certainly in males, and may
account for over 20% of the disease in some populations (27). The
third world is targeted by tobacco-pedlars for the promotion of
cigarettes, and a rising incidence of AML will be one part of the
large increases of cancer, mostly tobacco-related, foreseen in developing
countries in the coming decades. Burkitt's lymphoma, other non-Hodgkin's
lymphomas, Hodgkin's disease, myeloma and CLL all occur in the young
or relatively young in Africa: alkylating agents are prescribed
commonly in their treatment and are causatIvely associated with
AML, so that it can be anticipated that this disease will have higher
than expected incidence in patients who have receIved cytOtOXIC
therapy (2). Prognosis for patients with AML in sub-Saharan Africa
treated WIth conventional cytotoxic therapy remains uniformly poor,
with median survival about 9 months (25). The facilities for bone
marrow transplant are not available.
CHRONIC MYELOID LEUKAEMIA
The annual incidence of CML is around 1 per 10 high 5 throughout
the world; the male to female ratio is about 1:5:1, with a slightly
higher rate amongst black males (29). The peak of frequency of diagnosis
is Africa is in the fifth decade, as it is in the western world,
but more patients are younger than 40 years than older, reflectIng
the age distribution of the population. The disease is not uncommon
even in childhood, about 10% of patients in Nigeria and 19% in Sudan
being below 15 years of age ( 1, 2). African patients respond as
expected to conventional cytotoxic therapy.
CHRONIC LYMPHATIC LEUKAEMIA
Epidemiology Both the gender and age distributions of CLL in tropical
Africa differ greatly from those in the western world (30). In west
Africa, the male to female ratio is 1:1, as compared to 2:1 in the
western world. CLL is common under the age of 40 years and may occur
as early as the teens in Africa, whereas it is rare in young western
adults. There is arising frequency in women up to the end of their
reproductive period of life, and CLL is seen twice as commonly in
women than in men below the age of 45 years. Over 45 years, the
male to female ratio is : 1, as in the western world. A similar
pattern is seen in east Africa, but is not so pronounced. All the
younger patients with CLL are of low socioeconomic status or come
from rural areas.
It is postulated that the unique pattern of CLL in tropical Africa
is the result of recurrent malaria and other infections, leading
to both a depression of T -cell control of B-cell proliferation
and direct antigenic and mitogenic stimuli to B-cell proliferation:
there is a greatly enlarged polyclonal B-cell pool, especially in
subjects living in rural areas and in poor hygienic conditions:
the physiological depression of cell mediated immunity of normal
pregnancy leads to an increased susceptibility to malaria, and also
to certain bacterial and viral infections, as well as reducing surveillance
for somatic mutations: all these factors ( endemic malaria, the
transmission of other infections which could include oncogenic viruses,
numerous pregnancies) favour the proliferation of a large pool of
B-cells in which there is a relatively high chance of somatic mutations
leading to a monoclonal proliferation of B-CLL. The hyper-reactive
malarial splenomegaly syndrome (HMS), previously called the tropical
splenomegaly syndrome (TSS), is a condition in which there is probably
a genetically determined malarial-triggered suppression of T -cell
control of B-cell proliferation, resulting in a grossly exaggerated
B-cell response to recurrent malaria: the chances of developing
CLL should be in theory greater in patients with HMS than in the
general population and it has been demonstrated recently that clonal
lymphoproliferation can complicate HMS, and could lead to the evolution
of CLL or splenic lymphoma with villous lymphocytes (31,32).
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