A clinical study on the prevalence of leukemia  in patients observed  in Zimbabwean major hospitals.In the period December 1985 to November 1988 inclusive, 137 cases of acute leukaemia were diagnosed in patients of all age groups: 129 cases came under our direct care, and a further eight cases were diagnosed on blood and marrow films sent from elsewhere (four from Mpilo Hospital (Bulawayo) and four from other hospitals)

Levy, L.

Mandisodza, A.

Mukiibi, J.M.

Nkrumah, F.K.

Paul, B.

Central African Journal of Medicine

English

IDS OpenDocs

The
Central African 
Journal 
ofMedicine
Supplementary Issue to 1992 Volume 38,
1991 University of Zimbabwe Annual Research Day
A three-year prospective 
study of 137 cases of acute 
leukaemia in Zimbabwe
B PAUL, J M MUKIIBI, A MANDISODZA, L 
LEVY and F K NKRUMAH
SUMMARY
We studied 137 cases o f acute leukaemia seen 
between December 1985 and November 1988, using 
traditional sta in ing techniques together with 
cytochemistry and in cases o f probable acute 
lymphoblastic leukaemia (Sudan Black negative) by 
immunophenotyping. Not all tests were carried out in 
every case (some cases o f ALL could only be 
classified as T or non-T).
Paediatric group (agc<14 yrs): 75 cases —  acute 
lym phoblastic leukaem ia 52 , acute m yeloid  
leukaemia 18, acute undifferentiated leukaemia 5. 
Peak incidence in 5 -9  year group. Malc:Female ratio 
= 1,7:1. acute myeloid leukaemia was associated with 
chloromas in 2 cases (11 pc).
Adult group: 62 cases —  acute lymphoblastic 
leukaemia 23, acute myeloid leukaemia 36 and acute 
undifferentiated leukaemia 3. Peak incidence in 
50-54 age group. Male:Fcmale ratio = 1:1,2.
Acute lymphoblastic leukaemia subtypes (all ages) 
T 16, Common 20, Null 12, ‘non-T’ 16, B cell 0, 
untyped 11.69 pc were of L2 morphology. In T-ALL, 
11 had thymomas and Malc:Female ratio = 15:1. 
Malc:Femalc ratio for ‘non-T’ = 1,5:1.
Acute myeloid leukaemia subtypes (all ages) Ml 
3, M2 8, M3 14, M4 19, M5 8, M6 2, M7 1.
Overall incidence o f acute leukaemia appears 
increased at 0,91 per 100 000 per annum from 
previous studies in Zimbabwe. Common ALL (mean
CENTRAL AFRICAN
JOURNAL OF MEDICINE
Department o f Haematology, Medicine and Paediatrics 
University o f Zimbabwe School o f Medicine 
P 0  BoxA178
Avondale, Harare, Zimbabwe 
Correspondence 
B Paul
Dept o f Haematology 
Victoria Hospital 
Workshop 
Notts S80 2BN 
UK
age = 1 3  years) is an emerging problem and now 
outnumbers T-ALL (mean age = 10 years). This may 
be related to a general improvement in living  
standards and health in Zimbabwe.
INTRODUCTION
There is a general paucity o f information on the 
epidemiology o f acute leukaemia in Africa especially 
s in c e  th e e x p lo s io n  o f  k n o w le d g e  in c e l l  
differentiation that has occurred over the past few 
years —  a bibliography was recently published.1 An 
accurate diagnosis is essential if these disorders are 
g o in g  to be treated a g g r e ss iv e ly , and a lso  
classification relates to prognosis. The pattern of 
leute leukaemia may be changing in some parts of 
Africa and this may give some actiological clues.
Many studies have been retrospective surveys of 
hospital records3'4,5 and m ost were before the 
introduction o f cell marker studies. We have carried 
out a prospective study using traditional staining 
tech niq ues together with cy toch em istry  and 
immunophenotyping.
MATERIALS AND METHODS
In the period December 1985 to November 1988 
inclusive, 137 cases o f acute leukaemia were 
diagnosed in patients of all age groups: 129 cases 
came under our direct care, and a further eight cases 
were diagnosed on blood and marrow films sent from 
elsewhere (four from Mpilo Hospital (Bulawayo) and 
four from other hospitals).
Morphological classification was based on the
French-Amcrican-British system by examining
6 7 8Gicmsa stained blood and marrow smears. ' ’ In the 
case of acute lymphoblastic leukaemia a scoring 
system was used to differentiate between L I , L2 and 
L3 morphology.7
Further studies carried out included Sudan Black 
B and Periodic Acid Schiff stains by routine 
methods. Myeloperoxidase, chloroacetate esterase, 
a-naphthyl acetate esterase, and acid phosphatase 
were carried out by commercial kits following the 
manufacturer’s instructions (Sigma, $t Louis, USA). 
Im m u n op h en o ty p in g  in c lu d ed  term in al 
d e o x y n u c le o t id y l tran sferase  by in d irect  
immunofluorescence (polyclonal antibody, ScraLab, 
Crawley, UK), and sheep E rosettes using fresh
Vol. 38, No. 3, March, 1992
95
CENTRAL AFRICAN
JOURNAL OF MEDICINE
Vol. 38, No. 3, March, 1992
F ig u re  I: In c id e n c e  o f  a c u te  leu k a em ia
incidence of Acute Leukaemia
R a te /100,000 per year
untreated washed red cells from African sheep ol the 
university flock by a standard technique.!0
Monoclonal antibodies (Ortho, Raritan, USA) 
were used by either indirect immunofluoresccnt or 
indirect immunoperoxidase techniques (Ortho) with 
the following specificities CD 3 (OKT3), CD10 
(OK-CALLa), CD24 (OKB2), HLAclass II (OKDR) 
and CD13 (UCHM1). Some tests were carried on 
cells in suspension after Ficoll separation or on direct 
smears if little material was available together with 
appropriate controls. Polyclonal antikappa, lambda, 
and mu (ScraLab) was used to detect surface or 
c y to p la s ic  im m u n o g lo b u lin  by d irect  
immunofl.uorescent techniques.10 A resu lt w as 
considered positive if greater than 10 pc of blast cells 
reacted.
Not all tests were carried out on each patient to 
conserve expensive reagents —  where lcukacmic 
c e l ls  had o b v io u s  Sudan B la ck  p o s it iv ity  
immunophenotyping was not carried out. Some cases 
of acute lymphoblastic leukaemia could only be 
classified as T cell (Sudan Black negative, Sheep E 
R osette p ositive , loca lised  A cid Phosphatase 
positive), or non-T cell type (Sudan Black negative,
Sheep E Rosette negative, dittuse or negative Acid 
Phosphatase).
M6 subtype was diagnosed by PAS positivity in the 
erythroblasts and M7 by PAS reaction and reticulin 
staining of the trephine biopsy.
Incidence rates are based on the sex and age 
distribution of the whole population (1982 census) 
and that the catchment population for Parirenyatwa 
Hospital at the time of the study was five million. 
Student’s V  test and chi squared tests were used for 
statistical analysis. White cell counts were log 
transformed for analysis.
RESULTS
During the three-year study period, 137 cases of acute 
leukaemia were seen: 75 (55 pc) in the paediatric 
group (aged 14 years or less) and 62 (45 pc) in the 
adult group (aged 15 years or more). This gives an 
o v e r a ll in c id e n c e  o f  acu te leukaem ia of 
approximately 0,9 per 100 000 per annum. The 
pattern based on quinquennial groups is shown in 
Figure I. Two peaks are seen at the age of 5-9 and 
50-54 years with incidence rats of 1,14 and 1,73 per 
100 000 per annum respectively.
96
CENTRAL AFRICAN
JOURNAL OF MEDICINE
Vol. 38, No. 3, March, 1992
Table I: S ea so n  v a r ia tio n  o f  a c u te  le u k a e m ia
Nov-Jan Feb-A pr M ay-Jul A ug-O ct
ALL 21 22 14 21
AL 36 3 A 33 34
ALL = Acute lymphoblastic leukaemia 
AL = Acute leukaemia (all types)
The month of presentation is shown in Table I. Data 
have been collected into three-month periods as the 
numbers in any one month arc low. November-April 
cover the rainy season and May-October the dry 
season in Z im babw e. Few er ca ses  o f  acute  
lymphoblastic leukaemia were seen in the May-July 
period, but this is not a significant difference (X2 = 
2,1, p >0,5).
A cu te  ly m p h o b la stic  leu k a em ia  w as the 
commonest type (69 pc) in the paediatric group 
(Table II). Two o f 18 cases o f acute m yeloid  
leukaemia were associated with an orbital chloroma. 
Acute myeloid leukaemia was the commonest type in 
adults (58 pc) [Table III],
Table II: S u b ty p e s  o f  p a e d ia tr ic  a c u te  le u k a e m ia
M F M :F ratio Total (pc)
ALL 36 16 2,3:1‘ 52 (69)
AML 911 9 1:1 18 (24)
AUL 2 3 1:1,5 5 (7)
Total 47 26 1 ,7 :1 " 75 (100)
\  2 chloroma *X2 = 7.65 p<0,01
" X 2 = 4,81 fx0,05
Table III. S u b ty p e s  o f  a d u lt  a c u te  leu k a em ia
M F M :F ratio Total (pc)
ALL 14 9 1,6:1 23 (37)
AML 12 24 1:2* 36 (58)
AUL 2 1 2:1 3 (5)
Total 28 34 1:1,2” 62 (100)
* X2 = 4,0 p<0,05 "  X2 = 1,08 p = NS
Commonest types o f acute myeloid leukaemia (Table 
IV) were myelomonocy tic (35 pc) and promyclocytic 
leukaemia (25 pc) with 8/14 being the hypogranular 
varient (M3b).
Table V shows the subtypes o f acute lymphoblastic 
leukaemia. Common ALL was the most frequent 
followed by T cell disease. Most cases of acute 
lymphoblastic leukaemia had L2 morphology (Table
VI). Most (69 pc) of T-ALL cases were associated 
with a large anterior mediastinal mass on chest X-ray 
and there is a marked male predominance in this 
group.
T able IV: S u b ty p e s  o f  a c u te  m y e lo id  le u k a e m ia  (a ll  
a g e  g ro u p s)
Type n PC W BC (SD)
Ml 3 5 44,8 (32,81
M2 8 15 42,2 (46,5)
M3* 14 25 56,1 (67,9)
M4 19 35 85,1 (148,6)
m51i 8 15 124,1 (202,2)
M6 2 4 35.9 —
M7 < 2 10,5 -
*M3a = 6 U 3 b = e
f  M5a = 6 M5b = 2
WBC = at presentation x tCr/1 (SO)
T able V: S u b ty p e s  o f  A L L  (a ll  a g e  g r o u p s )
n pc M :F m ean W B C (SD)
T cell* 16 21 15:1 129,1 (205,0)
Common 20 27 1:1 56,8 (110,8)
Null 12 16 3:1 149,0 (261,5)
Non-T 16 21 1:1,3 84,7 (124,5)
Untyped 11 15 1,8:1 141,9 (246,9)
Bcell 0 0
* 11 (69 pc) associated with thymoma on CXR
WBC T v CALL t = 3,44p = <0,01
WBC T v Null t = 2,79pcO.Ot
WBC Null v CALL t = 7,68 p = <0,001
T able VI: M o r p h o lo g y  a n d  PA S r e a c tio n  o f  A L L  (a ll
a g e  g r o u p s )
L2 =  23 (31 PC) P A S pos = 27  (37  pc)
L2 = 52 (69 pc) PAS ng = 46 (63 pc)
L 3 - 0 Not done = 2
Sixty three per cent of acute lymphoblastic leukaemia 
cases were PAS negative, though 16 o f 20 (80 pc) of 
common ALL were PAS positive. Thus if  PAS 
positive cases are considered as probable common 
ALL and are added to the known common ALL cases, 
the proportion o f common ALL rises to 37 pc. The 
sex ratio is equal in the Common ALL group.
There was a small group o f undifferentiated 
leukaemia (no myeloid or lymphoid markers on 
cytochemistry and immunophenotyping), with all
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CENTRAL AFRICAN
JOURNAL OF MEDTCINE
Vol. 38, No. 3, March, 1992
having a L2 morphology. Mean presentation WBC 
87,9 x 109/1; SD 103,8 (n = 7).
DISCUSSION
Previous studies o f acute leukaemia have been 
reported from Zimbabwe (formerly Rhodesia). 
Lowe’s study covered a 5-year period (1967-72) —  
46 cases were seen (acute lymphoblastic leukaemia 
14, a cu te  m y e lo id  leu k a em ia  21 , acu te  
undifferentiated leukaemia 11) giving an overall 
incidence of about 0,3/100,000/year which is much 
lower than the present study (0,91).4 For the period 
1980-82, 63 cases o f acute leukaemia were seen 
(acute lymphoblastic leukaemia 14, acute myeloid 
leukaemia 49) though some paediatric cases were not 
included.11 This study showed a male predominance 
of acute lymphoblastic leukaemia (2:1) similar to the 
present series, but classification by subtype was not 
reported —  overall incidence of acute leukaemia of 
0,7/100 000/ycar was again lower than our current 
survey.
The increasing incidence may in part reflect better 
diagnostic facilities, but there is probably a true 
increase in the incidence o f acute leukaemia in 
Zimbabwe as noted in other countries. These 
Zimbabwean studies are not true population based 
surveys and thus the absolute figures must be treated 
with caution.
The incidence o f acute leukaemia is still low in
comparison with the United Kingdom (eg age 0 -4
acute lymphoblastic leukaemia = 5,0, acute myeloid
leukaemia = 0,8; age 55-65 acute lymphoblastic
leukaemia = 0,7, acute myeloid leukaemia = 5,7.100
000/ycar).13’14 Lower rates of acute lymphoblastic
leukaemia arc noted in American blacks, Jamaicans 
12 15and Nigerians. ’
Environmental factors may be important in the 
aetiology o f some types o f acute leukaemia.2 We 
exam ined the seasonal incidence by month o f  
presentation to see if this gives any clues. However, 
there is no significant trend in our patients despite a 
slight fall in part o f the dry season (May-July) nor in 
the subtypes o f acute lymphoblastic leukaemia.
All the major FAB subtypes of acute myeloid 
leukaemia were identified with M4 being the most 
common (35 pc). We were surprised at the number o f  
M3 (25 pc) o f which 8/14 were the hypogranular 
varient. Previous studies have shown marked
variation in distribution which in part may reflect lack 
of reproducibility of some FAB criteria —  M3 
averages 10 pc of acute myeloid leukaemia.16 All our 
cases were classified by one author (BP) and M3 has 
characteristic morphology. A previous study in 
Zimbabwe also gave a relatively high incidence of 
M3 —  4/17 (24 pc).4 Many patients presented with 
high blast cell counts and these were highest in the 
M5 group (mean 124 x 109/1).
Two boys presented with an orbital chloroma with 
M3 and M4 AML —  a 10 pc incidence o f chloroma 
in childhood acute myeloid leukaemia. A higher 
incidence of chloroma has been reported from West 
Africa (-50  pc),17 East Africa (-23 pc),5 and in South 
African blacks (-24  pc).19
Most cases o f childhood acute lymphoblastic 
leukaemia (75 pc) were o f L2 morphology which is 
higher than 10-15 pc in European populations.16 
Other poor prognostic features included the majority 
being PAS negative, 13/44 (30 pc) being T-ALL, and 
most presenting with a high WBC. The mean age of 
T-ALL was 10 years (SD = 11,6). The age peak for 
Common-ALL is also older than in Europeans — 
mean 13,3 (SD 9,0) years. Common-ALL is reported 
to be rare in Africa compared to T-ALL. ,19'20 
However, we found 20/66 (30 pc) typed as common 
ALL (all ages) and 20 pc o f paediatric cases.
Eighty per cent o f Common-ALL were PAS 
positive so this remains a good marker in the absence 
of more sophisticated techniques. The incidence of 
Common-ALL is still less than in European children 
(-80  pc) and adults (-50  pc).16 No cases o f L3 ALL 
were found in this study period though 5 cases of 
secondary marrow invo lvem en t by Burkitt’s 
lymphoma were seen.
The null-ALL cases are probably more accurately 
called “early B-precursor ALL” , but this needs to be 
confirmed by immunoglobulin gene rearrangement 
studies.
It is possible that the improving socioeconomic 
position of black Zimbabweans is now associated 
with an increasing incidence o f common ALL as 
noted in other countries. ’ Continued long teim 
studies including karyotyping are needed to confirm 
our findings. There is also an overall increase in the 
incidence o f acute leukaemia in Zimbabwe which is 
relevant to the allocation o f scarce resources — the 
results o f treatment will be reported separately.
98
ACKNOWLEDGEMENTS
Thanks to Andrea Vardy for typing the manuscript
and Christine Gwanzura for technical assistance.
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A three-year prospective study of 137 cases of  acute leukaemia in Zimbabwe

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A three-year prospective study of 137 cases of acute leukaemia in Zimbabwe

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