Chronic lymphocytic leukaemia (CLL) in Central Africans.

OBJECTIVE: To document the clinical and haematological features of chronic lymphocytic leukaemia (CLL) in Central Africans. DESIGN: Prospective descriptive analysis. SETTING: Tertiary referral teaching hospitals. SUBJECTS: 48 Zimbabweans and 27 Malawians formed the basis of this analysis. RESULTS: There were 75 patients (40 males and 35 females) studied and their ages ranged from 32 to 78 years with a mean +/- s.d. of 56.8 +/- 10.1 years. The peak age incidence of 26.7% occurred between 60 to 64 year old and 21.3% were below 50 years. The major clinical findings included: splenomegaly (68%); hepatomegaly (37.3%); anaemia (34.7%); lymphadenopathy (33.3%) and nine (12%) patients were diagnosed incidentally. The majority of patients (78.7%) had Rai stage III and IV and only seven (9.3%) patients were in stage 0. Of the 32 patients treated with chemotherapy, 25.9% and 59.3% achieved complete or partial remissions respectively. Six patients were still alive after a follow up period of a mean +/- s.d of 39.3 +/- 24.4 months; five were lost to follow up after a mean +/- s.d period of 28.6 +/- 18.8 months and 16 were dead after a mean +/- s.d. period of 25.7 +/- 19.1 months. The main causes of death in the treated group were septicaemia in six, pneumonia in four and tuberculosis in three. In the untreated group of 43 patients, two refused therapy, four died shortly after diagnosis and 37 were lost to follow up. CONCLUSIONS AND RECOMMENDATIONS: Although the study has disclosed that CLL is not rare in central Africans and its presentations are similar to cases reported in the literature, the majority of patients seek medical treatment late. Optimal therapy is impossible due to lack of chemotherapy and supportive services..Therefore, it is recommended that tertiary referral centers in African health systems should be equipped for better management of CLL patients.

Chronic myeloid leukaemia in central Africans.

OBJECTIVES: To document the pattern of presenting clinical and haematological features of chronic myeloid leukaemia (CML) in central Africans and evaluate the clinical consequences of treating the disease with chemotherapy. DESIGN: Prospective descriptive analysis of clinical and haematological data. SETTING: Departments of Haematology of tertiary referral centres and teaching hospitals. MATERIALS AND METHODS: Prospective clinical and haematological data were collected on 150 central Africans (90 Zimbabweans and 60 Malawians) using modern Coulter counters and standard up-to-date haematological procedures and the results analysed using predetermined criteria and the top-desk Scientific Calculator Model HP 48GX, Texas Instruments, USA. RESULTS: There were 150 CML patients studied. Males predominated in a ratio of 1:5:1. The youngest patient was 10 years and the oldest 77 years with a mean +/- s.d. of 38.9 +/- 14.7 years. The peak age incidence of 47.3% occurred between 21 to 40 years. The Ph chromosome was found in 19 of the 20 patients studied. Although complaints attributed to splenic enlargement were the most common symptoms, several unusual clinical features were encountered viz: hepatomegaly (26%), bleeding (12%), significant lymphadenopathy (11.3%), purpura (3.3%), skin infiltration (2.7%), cardiac failure (2.7%) and 14.7% were diagnosed incidentally. Symptoms such as fatigue, headaches and weight loss were associated with greater degrees of leucocytosis, severe to gross splenomegaly and lower haemoglobin levels. The severe to gross splenomegaly which occurred in 68(45.3%) suggests that patients in this part of the world seek medical advice rather late in the disease. The median survival times of 65,47 and 39 months respectively for alpha interferon, hydroxyurea and busulphan are in agreement with those of previous larger series from other parts of the world. CONCLUSIONS: The study has revealed that the presenting pattern of clinical and haematological features of CML is changing probably due to the advent of modern clinical practice coupled with increased physician density, greater awareness of disease among clinicians besides other reasons. However, optimal treatment is not possible for the majority of patients due to lack of chemotherapeutic agents and supportive care. RECOMMENDATION: Referral centres in African health systems should be equipped for better management of CML patients.

Leukaemia at Queen Elizabeth Central Hospital in Blantyre, Malawi.

OBJECTIVES: To determine the patterns of leukaemias seen in Malawians at Queen Elizabeth Central Hospital (QECH) and to compare the findings with those from elsewhere. An overview of the problems encountered in the management of leukaemia in developing countries especially those in sub-Saharan Africa are highlighted. DESIGN: Retrospective descriptive analysis of consecutive leukaemia cases seen from January 1994 through December 1998. RESULTS: Of the 95 leukaemia patients diagnosed during the study period, childhood (0-15 years) leukaemia occurred in 27 (28.4%) patients while adulthood (above 15 years) leukaemia accounted for 68 (71.6%) patients. The main leukaemia types were: acute lymphoblastic leukaemia (ALL) 14 (14.7%), acute myeloblastic leukaemia (AML) 25 (26.3%), chronic myeloid (granulocytic) leukaemia (CML) 32 (33.7%), chronic lymphocytic (lymphatic) leukaemia (CLL) 22 (23.2%) and hairy cell leukaemia (HCL) two (2.1%) patients. Most of the acute leukaemia (AL) cases occurred in the six to 15 year age bracket with a male preponderance. In ALL, lymphadenopathy was the commonest presenting feature followed by pallor (92.9%) while in the AML group, pallor occurred in 80% of cases. Abdominal swelling (87.5%) due to splenomegaly (81.3%) were the main clinical features in the CML group whereas lymphadenopathy (63.6%) followed by splenomegaly (59.1%) were the dominant presenting features in CLL. Haematologically, although leucocytosis characterised both acute and chronic leukaemias, most cases of acute leukaemia presented with more severe anaemia (Hb < 7 g/dl) and marked thrombocytopenia (Platelet count < 50 x 10(9)/l) than the chronic leukaemias. CONCLUSIONS AND RECOMMENDATIONS: The study shows that leukaemias are not rare in Malawi and cases which were diagnosed in this series probably only represent the tip of the iceberg. While there is need to increase diagnostic awareness among clinicians and laboratory staff, the severe chronic shortage of cytotoxic drugs and lack of supportive care facilities commonly encountered in developing countries should be realistically addressed through cost-sharing, cost recovery, adequate government subvention and donations from charitable organisations.

Neonatal haematology in Zimbabwe. II: The red cell and white cell parameters.

Red cell and white cell parameters were determined in 600 (310 male and 290 female) normal Black Zimbabwean neonates with a mean +/- sd birth weight of 3.0 +/- 0.4 (range 2.04 to 4.50, median 3.0) kg using a Coulter Counter Model S Plus. Cord anaemia (cord Hb < 13.5 gdl-1) was detected in 60 (10 pc) of the neonates. Although the male babies were significantly heavier than the females (p = 0.004), there were no significant differences (p > 0.05) in the red cell and white cell indices between the two sexes. When the haematological parameters of the 540 (90 pc) non-anaemic (cord Hb > or = 13.5 gdl-1) neonates were analysed, the mean +/- sd values which may serve as local reference standards were: Hb 15.2 +/- 1.8 (range 13.5 to 19.4) gdl-1, Hct 47.3 4.9 (range 38.6 to 60.3) pc, MCV 107.8 +/- 9.4 (range 88.8 to 134.3) fl, MCH 31.9 +/- 3.4 (range 25.2 to 45.2) pg, MCHC 32.9 +/- 1.3 (range 30.0 to 38.3) gdl-1, nucleated red blood cells 6.1 +/- 5.9 (range 0 to 55) per 100 white blood cells, reticulocyte count 5.0 +/- 1.9 (range 0 to 24.0) pc, total leucocyte count 13.8 +/- 4.4 (range 4.6 to 132.8) x 10(9)l-1; differential count: neutrophils 7.30 +/- 2.90 (range 1.72 to 18.02) x 10(9) l-1, lymphocytes 5.67 +/- 2.47 (range 0.98 to 16.14) x 10(9) l-1, monocytes 0.81 +/- 0.83 (range 0 to 5.58) x 10(9) l-1, 1 and eosinophils 0.08 +/- 0.13 (range 0 to 0.72) x 10(9)l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Some haematological parameters in Malawian neonates.

Studies of haematological parameters were performed on 366 (177 male and 189 female) normal Malawian neonates with mean +/- s.d. birthweight of 2.99 +/- 0.37 (range 2.1-4.0) kg using a Nova Cell Track, Model Nova CT11. Cord anaemia (Cord Hb < 13.5g dl-1) was detected in 100 (27.3%) of the neonates. It was also shown that although the male babies had a significantly higher erythrocyte protoporphyrin level (p < 0.001) than the females, there were no significant differences (p > 0.05) in the red cell, white cell and platelet indices between the two sexes. When the haematological parameters of the 266 (72.7%) non-anaemic (Cord Hb > 13.5g dl-1) neonates were analysed, the mean +/- s.d. values which may serve as local reference standards were: Hb 16.0 +/- 1.7 (range 13.5-21.3) g dl-1, Hct 47.0 +/- 6.0 (range 36.5-67.5) percent, MCV 112.6 +/- 8.9 (range 72.2-131.0) fl, MCH 31.9 +/- 5.5 (range 24.4-48.5) pg, MCHC 33.5 +/- 2.8 (range 29.1-48.9) g dl-1 reticulocyte count 6.9 +/- 3.6 (range 1.2-25.0) percent, free erythrocyte protoporphyrin 3.3 +/- 0.9 (range 1.9-7.7) mgs ZPP gm-1 Hb, platelet count 269.9 +/- 57.7 (range 134.0-454.0) x 10(9) l-1 and total leucocyte count 12.3 +/- 4.8 (range 5.5-35.3) x 10(9) l-1. Further analysis of the differential wbc count disclosed normal levels of eosinophils and neutrophils similar to those given in standard haematology textbooks for Caucasian neonates; thus strengthening the belief that eosinophilia and relative neutropenia previously reported in adult Africans is not of genetic origin, but rather an acquired phenomena.

Spectrum of childhood cancers in Malawi 1985-1993.

An analysis of seven hundred and ninety one children aged 0.2 to 14 years with confirmed malignant disease recorded by the Malawi National Cancer Registry over a period of 9 years is presented. Childhood cancer constituted 6.9% of all malignancies recorded during the study period. The top ten neoplasms in descending order of frequency were: non-Hodgkin's lymphoma 434 (54.9%), retinoblastoma 89 (11.3%), nephroblastoma 50 (6.3%), epithelial carcinoma 45 (5.7%), Hodgkin's disease 38 (4.8%), soft tissue sarcoma (excluding Kaposi): 34(4.3%), Kaposi's sarcoma 32 (4.0%), malignant tumours (not specified): 20 (2.5%), acute leukaemias 18(2.3%) and osteogenic sarcoma 16 (2.0%). Some differences noted in the pattern of neoplasms in this study from those of developed and developing African countries are discussed. The findings highlight the most common childhood malignancies in Malawi where intense research should be directed so that meaningful and cost effective therapeutic intervention programmes can be planned and developed.

Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe.

In a study of the pathogenesis and clinical features of megaloblastic anaemia in southern Africa, we evaluated 144 consecutive Zimbabwean patients with megaloblastic haemopoiesis. Vitamin B12 deficiency was diagnosed in 86.1% of patients and was usually due to pernicious anaemia; isolated folate deficiency accounted for only 5.5% of cases. Anaemia was present in 95.8% of patients; the haemoglobin (Hb) was < or = 6 g/dl in 63.9%. Neurological dysfunction was noted in 70.2% of vitamin B12-deficient patients and was most striking in those with Hb values > 6 g/dl. Serum levels of methylmalonic acid, homocysteine, or both, were increased in 98.5% of patients. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe and, contrary to textbook statements, is often due to pernicious anaemia. Isolated folate deficiency is less common. As reported in industrialized countries 75 years ago, anaemia is almost always present and often severe. Neurological dysfunction due to vitamin B12 deficiency is most prominent in patients with mild to moderate anaemia.

Neonatal haematology in Zimbabwe. I: The platelet parameters.

Platelet parameters were determined in 600 full term healthy Zimbabwean neonates using a Coulter Counter Model S Plus. The mean +/- s.d. values obtained with ranges were: Platelet count 235 +/- 67 (range 100-410) x 10(9) l-1; Mean Platelet Volume (MPV) 9.5 +/- 1.0 (range 7.1-13.9) fl; Plateletcrit (PCT) 0.269 +/- 0.058 (range 0.142-0.524) and Platelet Distribution Width (PDW) 16.8 +/- 1.0 (range 12.2-19.8). Although platelet counts in this study were comparable to those established by others in both Black and Caucasian infants, the female Zimbabwean neonates had significantly higher counts than the males (p < 0.001). An inverse relationship between the number of circulating platelets and their MPV was also observed. Further studies are needed to delineate the range of normality of these platelet measurements in the African neonate so that abnormal cases can be adequately screened, investigated and appropriately treated.

Myelodysplastic syndromes (MDS) in Central Africans.

Forty two patients who were seen and satisfied the French-American-British (FAB) diagnostic criteria for myelodysplastic syndromes (MDS) over a 6-year period at the University of Zimbabwe's Department of Haematology, Harare, are presented. Their overall ages ranged from 29 to 75 years with a mean +/- SD of 57.8 +/- 11.2 years. Males outnumbered females with a male to female ratio of 1.2:1. Refractory anaemia (RA) occurred in 33.3%; refractory anaemia with ringed sideroblasts (RARS) in 16.7%; refractory anaemia with excess blasts (RAEB) in 21.4%; refractory anaemia with excess blasts in transformation (RAEB-T) in 16.7% and chronic myelomonocytic leukaemia (CMML) in 11.9% of the patients. In 90.5% the disease was primary and in 9.5% prior exposure to myelotoxic agents resulted in secondary MDS. The study reveals that MDS as a cause of anaemia in the African population is usually hidden in the big number of well known anaemias due to rampant malaria, malnutrition and a host of nutritional deficiencies. There is therefore the need to increase diagnostic awareness among our clinicians about the existence of these disorders.

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

We studied 137 cases of acute leukaemia seen between December 1985 and November 1988, using traditional staining techniques together with cytochemistry and in cases of probable acute lymphoblastic leukaemia (Sudan Black negative) by immunophenotyping. Not all tests were carried out in every case (some cases of ALL could only be classified as T or non-T). Paediatric group (age less than or equal to 14 yrs): 75 cases--acute lymphoblastic leukaemia 52, acute myeloid leukaemia 18, acute undifferentiated leukaemia 5. Peak incidence in 5-9 year group. Male: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:Female 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 Male:Female ratio = 15:1. Male:Female ratio for 'non-T' = 1.5:1. Acute myeloid leukaemia subtypes (all ages) M1 3, M2 8, M3 14, M4 19, M5 8, M6 2, M7 1. Overall incidence of acute leukaemia appears increased at 0.91 per 100,000 per annum from previous studies in Zimbabwe. Common ALL (mean age = 13 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.

Megaloblastic anaemia in Zimbabwe: spectrum of clinical and haematological manifestations.

An analysis of 100 cases (43 males and 57 females) with confirmed megaloblastic anaemia is presented. The age distribution showed two peaks with 18% in the third and fourth decades and 25% in the seventh decade. Anaemia of moderate to severe degree occurred in all patients and accounted for the commonest triad of symptoms at presentation viz: weakness (73%); breathlessness (40%) and headaches (33%). Macrocytosis or macroovalocytosis and neutrophil hyper-lobulation were found in all cases; MCV greater than 100fl in 84%; pancytopenia in 47%; and megaloblastic haematopoiesis found in all patients varied from moderate to gross in severity. Thus, the finding of macrocytic anaemia with a high MCV particularly in excess of 100fl, neutrophil hypersegmentation, and characteristic megaloblastic changes in the bone marrow should dictate further appropriate investigations to help in establishing the specific diagnosis if appropriate therapeutic intervention is to be ultimately instituted.

Megaloblastic anaemia in Zimbabwe. II: Diagnostic significance of red cell indices in.

Studies of red cell indices viz: Rbc count, Hb, Hct ratio, MCV, MCH and MCHC were carried out in normal subjects (n = 62) and in patients with: B12 deficiency (n = 34); folate deficiency (n = 17); and B12 and folate deficiency (n = 18). Although these red cell parameters were diagnostically useful (2P less than 5 x 10(-3)) in distinguishing the patients' groups from the control group; they showed no ability to distinguish the deficient groups from each other. However, their practical and diagnostic significance as screening tests in the local environs is briefly highlighted.

Megaloblastic anaemia in Zimbabwe: the pernicious anaemias.

This study of 16 patients with pernicious anaemia (PA) (9 males and 7 females); serves as further evidence that the disease is not as infrequent in Africans as the literature stressing its rarity in the past appears to have suggested. The age-old preconceptions about racial incidence; age of onset; and absence of adequate laboratory facilities particularly in the African setting have hitherto greatly contributed to under-diagnosis of this disorder in Africans.

Haemophilia in Zimbabwe.

Of the 120 haemophiliacs diagnosed in Zimbabwe in 8 years, haemophilia A and Christmas disease accounted for 90% and 10% respectively (i.e. a ratio of 9:1). Although the clinical and laboratory parameters were essentially similar to those previously described in Caucasian, African and other populations in the World, sub-haemophiliac cases are probably still being missed particularly in very busy health centres where the index of suspicion is low and malnutrition and infectious disease predominate and therefore readily attract the attention of most health workers. However, with the steadily improving socio-economic status and decentralization of health care facilities, more of these cases are likely to be diagnosed. Major constraints in the diagnosis and management of haemophilia in an African setting are succinctly discussed; including home therapy; and the implications of recent findings of HIV sero-positivity. The study serves as evidence that haemophilia is common in Zimbabwe contrary to earlier published literature.

Autoimmune thrombocytopenic purpura (AITP) in Zimbabwe.

80 patients with autoimmune thrombocytopenic purpura (AITP) seen in Zimbabwe between January 1980 and December 1987 are presented. There was a female preponderance (male to female ratio of 1:1,9); and the mean age +/- s.d. was 18.1 +/- 14.5 (range 0.5 to 59) years. Seventy nine per cent of the acute AITP patients presented within the first decade of life; whilst 25% and 75% of the chronic AITP cases were seen below and above ten years respectively. Epistaxis was the commonest form of presentation; occurring in 70% of all cases. Platelet counts considered to be in the potentially dangerous level i.e. less than 40-50 X 10(9)/l were respectively found in 92% and 82% of the acute and chronic cases. The disease is not rare in Zimbabwe and presents with a picture identical with that previously described in Caucasian and other African populations.

The significance of 'dry tap' bone marrow aspirations in Zimbabweans.

Of the 2880 bone marrow examinations performed in a 3-year period in patients with diverse haematological and oncological disorders, 116(4%) patients exhibited 'dry tap' on routine marrow aspiration. However, when the Jamshidi-Swaim technique of trephine bone marrow biopsy was performed in these patients, the single commonest underlying pathological cause of 'dry tap' was found to be aplastic anaemia which accounted for 56(48.3%) of the cases. The diagnostic potential of the technique and its advantages particularly in a developing country are briefly high-lighted.

A prospective analysis of 620 bone marrow examinations in Zimbabwe: preliminary observations.

Of the 1,310 bone marrow examinations performed in a 16-month period in patients with diverse haematological, oncological and other disorders, 620 had sufficient data for analysis. Seventy-nine percent were from the two main hospitals viz: Parirenyatwa and Harare Central Hospitals. Investigation for anaemia (42.6 percent), staging of malignant disease (14.4 percent) and pancytopenia (10.3 percent) formed the commonest triad of indications for requesting the examination. There were 318 (51 percent) males, mean age +/- s.d. of 33.8 +/- 22.6 years (range 6 months to 80 years); and 302 (49 percent) females, mean age +/- s.d. of 32.6 +/- 20.7 years (range 6 months to 78 years) giving a male to female ratio of 1.1:1. Of the 620 patients studied, 452 (73 percent) were adults (M:F ratio of 1:1) mean age +/- s.d. of 42.8 +/- 17.3 years (range 16-80 years); and 168 (27 percent) were children (M:F ratio of 1.1:1) mean age +/- s.d. of 7.3 +/- 4.5 years (range 6 months to 15 years). The three commonest diseases in the combined (adults and children) group were: megaloblastic anaemia (25.2 percent); acute or chronic leukaemia (19.2 percent) and iron deficiency anaemia (10.5 percent). These three diseases respectively accounted for 32 percent, 17.5 percent and 10.8 percent of the cases in the adult (16 years and over) group; whereas in the paediatric (0-15 years) group, the top three diseases were: acute leukaemia (22 percent); Hodgkins and non-Hodgkins lymphomas (14.3 percent) and retinoblastoma (13.7 percent). These preliminary observations indicate some of the commonest haematological and oncological disorders where intense research might be beneficial to the community in Zimbabwe.

Myelodysplastic syndromes (MDS) in Zimbabweans--preliminary observations.

Twenty three Zimbabwean African patients who satisfied the French-American-British(FAB) diagnostic criteria for the myelodysplastic syndromes(MDS) at Godfrey Huggins School of Medicine, University of Zimbabwe, between July 1985 and June 1987 are presented. The disorders appear not to behave differently from those reported in Caucasian populations with regard to clinical and haematological features. Refractory anaemia (RA) occurred in 12 (52.2%) patients; refractory anaemia with ringed sideroblasts (RARS) in 4 (17.4%) patients; refractory anaemia with excess blasts (RAEB) in 2 (8.7%) patients; refractory anaemia with excess blasts in transformation (RAEB-T) in 3 (13.0%) patients; while chronic myelomonocytic leukaemia (CMML) was observed in 2 (8.7%) patients. In 19 cases, the disease was primary and in 4 prior exposure to myelotoxic agents resulted in secondary MDS. The clinical significance of recognising the disorders is briefly high-lighted together with our current treatment protocol.

Megaloblastic anaemia in Zimbabwe. 1: Seasonal variation.

Two hundred and ten patients who were confirmed to have megaloblastic anemia over a 2-year period were grouped according to the month of diagnosis. A distinct seasonal variation was detectable in the occurrence of megaloblastic anemia with a high prevalence in the wet season and a low prevalence in the dry season. The major factor postulated to be responsible for the seasonal fluctuations of the disorder is the concomitant diminution in the availability of folate-rich green vegetables; and not malaria transmission. As the dry season sets in and progresses, the frequency of megaloblastic anaemia cases increases reaching a peak during the wet season. It is suggested that an adequate supply of green vegetables like lettuce, spinach and cabbage throughout the year might lessen or even eliminate the seasonal variation of megaloblastic anaemia presently observed in this community.