Epidemiology of acute leukaemia in the Cape Province of South Africa.

Of 535 consecutive cases of acute leukaemia diagnosed in the Cape Province between 1978 and 1985, demographic data are incomplete in 75 black patients and they have had to be excluded from the spatial analysis. Of the remaining 460 cases, 223 (48.5%) occurred in white patients and 237 (51.5%) in those of mixed ancestry, classified as coloureds according to the Population Registration Act No. 30 of 1950. The average incidence was 2.12, 1.37 and 0.58/100,000 for whites, coloureds and blacks respectively. There was no temporal trend in the incidence of acute leukaemia between the three race groups. The median age for whites was 30 years and for the coloureds was 15 years, which is comparable to the 16 years for the black patients. The two-peak age distribution for leukaemia was seen in the white group, but was absent in the other two groups. This is accounted for by a different distribution in non-lymphoblastic as opposed to lymphoblastic subtypes. Furthermore, there was a disproportionately high frequency of acute progranulocytic leukaemia in the black patients, whereas the white and coloured groups were similar. There was a single, clearly defined macro-scale cluster restricted to white patients in Statistical Region 17 (SR-17). This exploratory study provides the first epidemiologic data for acute leukaemia in the Cape Province. It needs to be extended in order to verify these observations under more controlled circumstances and to seek evidence for some environmental factors that may account for the geographical cluster.

Reduction of neonatal blood eliminates the error induced by oxygen saturation in the spectrophotometric measurement of carboxyhaemoglobin.

Blood carboxyhaemoglobin (COHb) is a sensitive index of haemolysis and has been used in assessing the cause of different types of neonatal jaundice. Although the introduction of automated spectrophotometry provides rapid and accurate measurement in adult blood, in neonates oxygenated foetal haemoglobin (HbF) is thought to interfere with COHb measurement. In an attempt to eliminate this problem, the haemoglobin in neonatal blood was reduced with sodium dithionite. Cord blood from 50 infants was measured before and after reduction using an IL-282 co-oximeter; COHb levels fell after reduction. A significant positive correlation was found between apparent COHb% and oxygenation of cord blood. In contrast, no significant correlation was found between these parameters in adult blood where COHb values remained the same or rose slightly after reduction. In 20 healthy non-icteric neonates the mean reduced blood COHb value was not significantly different from the mean COHb value of 23 healthy non-smoking adults. We suggest that COHb in neonatal blood can be simply and accurately measured by the IL-282 co-oximeter provided that the blood is fully reduced.

Intussusception in haemophilia: a case report.

A case of intussusception in a haemophilic boy is described. The presumed cause was an intramural haematoma, which resulted in an ileocolic intussuception. This appears to be the first reported case which has been reduced by barium enema. It is suggested that this method, together with factor VIII replacement therapy as soon as possible after the development of symptoms, is the treatment of choice.

Peripheral gangrene in hypernatraemic dehydration of infancy.

Gangrene of the extremities complicating diarrhoea and severe hypernatraemic dehydration occurred in 6 infants. This is a rare complication of gastroenteritis, and its association with hypernatraemia does not seem to have previously been emphasized. The increased blood viscosity resulting from serum hyperosmolarity may have been responsible for the gangrene, and studies in our patients suggested that disseminated intravascular coagulation was present. In addition to fluid and electrolyte replacement, the infants were treated with heparin with some recovery of the affected extremities.

Acute promyelocytic leukemia. A childhood cluster.

Nine children with acute promyelocytic leukemia (APL) are presented. This series of children represents 7% of all acute leukemias and 21% of acute myelogenous leukemias seen during the same period at the Red Cross War Memorial Children's Hospital. These figures are much higher than the incidence quoted in other series of childhood leukemia. In addition, most of those children came from a confined geographic area. Two of the patients were younger than 2 years of age. The youngest patient with APL previously reported in the literature was 24 months.

The effect of glucose-6-phosphate dehydrogenase deficiency on the severity of neonatal jaundice in Cape Town.

A study was made of 3718 newborn infants with jaundice in excess of physiological levels. Prematurity, haemolytic disease, haematomas or infections were present in 1278 patients. Of the remaining 2440 neonates, 137 were deficient in glucose-6-phosphate dehydrogenase (G-6-PD) and 2303 had idiopathic hyperbilirubinaemia. Exchange transfusion was necessary in 59 (42,7%) of the patients with G-6-PD deficiency and in 426 (18,5%) of those with idiopathic hyperbilirubinaemia. Kernicterus occurred in 3 infants (2,2%) with G-6-PD deficiency and in 3 (0,13%) with idiopathic hyperbilirubinaemia. These findings indicate that G-6-PD deficiency contributes significantly to the severity of neonatal jaundice in the population group studied and should be regarded as a potentially dangerous condition.

Microcytic anaemia and haemoglobinopathy in Cape Town children.

Patients with thalassemia as well as those with iron deficiency typically have red cell microcytosis and hypochromia. In view of the large number of children with microcytic anaemia or an isolated microcytosis seen at the Red Cross War Memorial Children's Hospital, the frequency with which a low red cell mean corpuscular volume (MCV) was associated with the presence of thalassaemia or with an abnormal haemoglobin was investigated. Of 730 patients with an MCV of 60 fl or less, 46 (6.4%) were found to carry the beta-thalassaemia gene and 20 children (2.7 %) had an abnormal haemoglobin, most commonly haemoglobin E. The prevalence of thalassaemia was greatest among Coloured patients and abnormal haemoglobins were found exclusively in this group of children. The implications of these findings are discussed.

The relationship between prognosis and scintigraphic evidence of bone metastases in neuroblastoma.

The clinical records, scintigrams, radiographic skeletal surveys, and bone marrow aspiration and trephine results of 30 children with neuroblastoma were reviewed to determine the relationship between the result of the scintigram and the clinical outcome of the patient. The nine patients with normal radiographic skeletal surveys and no evidence of bone metastases on scintigraphy are alive and well having been off treatment for between 14 and 83 months. Eleven of the 13 children who had bone metastases on scintigraphy and radiography have died, as have seven of the eight patients who had positive scintigrams and normal radiographs. Scintigraphic evidence of bone metastases is associated with a very poor prognosis irrespective of the results of other investigations.

Haemoglobin Köln in Cape Town. A case report.

A 7-year-old patient presented with an acute haemolytic episode. Investigation showed the presence of an unstable haemoglobin (Hb), identified as Hb Köln. No other members of the family were affected. This disorder has occasionally been seen as a spontaneous mutation. This is the first report of Hb Köln in a South African family, although other unstable Hb variants have been described.

The classification of acute leukaemia in childhood.

In 1976 a French, American and British (FAB) cooperative group proposed a morphological classification of acute leukaemia which they hoped would prove more reproducible than previous classification. We present our preliminary experience with this classification, based on a 2-year study of 39 patients. Cytochemical and cell surface marker characteristics of the leukaemic cells were also studied. We found this classification to be satisfactory but some problems were noted in regard to its reproducibility, especially in acute lymphoblastic leukaemia (ALL). Cell surface markers were absent in the majority of cases of ALL ("null cell" type), while the remainder had T-cell characteristics. No B-cell types were seen. Cytochemical staining patterns clearly distinguished ALL from acute myeloid leukaemia (AML) and also helped to categorize AML into its subtypes. The implications of our finding are discussed.

Immunological studies in haemophilic children.

A majority of haemophiliacs who have received large-pool plasma products within the past 5 years have been exposed to the putative agent of the acquired immunodeficiency syndrome (AIDS)--HIV. It is not known what the risk of infection is among patients in South Africa. A study was made of 39 children with congenital coagulation disorders attending the Red Cross War Memorial Children's Hospital Haemophilia Clinic. All but 3 had been treated exclusively with small-pool lyophilised cryoprecipitate or a factor IX concentrate prepared by local blood transfusion services. Three patients had also received imported non-heat-treated commercial products FEIBA (Immuno), Autoplex, Proplex (Hyland) or Factorate (Armour). Absolute lymphocyte counts were normal in all patients but the OKT4/OKT8 ratio was reduced below 1.0 in 9 children including 2 of the 3 who had received commercial plasma concentrates. A high titre of HIV antibody was present in 2 of the 38 patients tested. Both of these children had received imported plasma concentrates and 1 shows some features of the AIDS-related complex. These results suggest that haemophiliacs who receive non-heat-treated commercial concentrates may be at greater risk of HIV infection than patients treated with locally produced plasma products.

Prevalence of human parvovirus B19 and TT virus in a group of young haemophiliacs in South Africa.

A well recognized hazard of transfusion with blood or blood products is the acquisition of a viral infection. Parvovirus B19 and transfusion transmitted virus (TTV) are two of several non-enveloped viruses that may on rare occasions be present in coagulation factor concentrates. The prevalence of these viruses in the South African Haemophilia population has not previously been studied. Thirty-nine Haemophiliac children were investigated for evidence of parvovirus and TTV infection. 26 boys with Haemophilia A had been treated with cryoprecipitate or intermediate purity factor VIII, and 13 boys with Haemophilia B had received prothrombin complex concentrates. All the plasma products were prepared from South African donors and were virally inactivated by heat or solvent/detergent since 1992. A control group of 32 children who had not been transfused were also studied. IgG antibodies to B19 were present in 29 of the 39 patients (74%), 18/26 (69%) with Haemophilia A and 12 of the 13 (85%) with Haemophilia B. None of the patients was IgM antibody positive but two children were PCR positive for B19 DNA. Of the control children, 47% had IgG antibodies to B19, but none were IgM antibody or B19 DNA positive. TTV viral DNA was found in 10.2% of patients and in 9% of the control group. The results indicate that our locally produced plasma products are not a significant source of TTV transmitted infection but may contribute to infection by B19 parvovirus.

Presentation and outcome of 25 cases of Fanconi's anemia.

Twenty-five children with Fanconi's anemia (FA) who attended the Paediatric Haematology Clinic of Red Cross Children's Hospital over the past 20 years were retrospectively reviewed. There was a female predominance with 17 girls and 8 boys in the group. The clinical features and laboratory data are enumerated. An unusually high prevalence of gastrointestinal anomalies (20%) was found. Seventeen children received an adequate trial of androgen therapy and in 12 the initial hemoglobin concentration increased by more than 2 g/dl or return to normal. Most patients subsequently required intermittent courses of androgens but three were able to stop treatment and maintain a normal hemoglobin concentration for from 3.5 to 20 years. Ten patients remain alive, of whom five had less severe hematological problems and did not require any treatment. The mean period of follow-up of the survivors is 8.7 years. Thirteen patients have died, with a mean time of 5.5 years from diagnosis to death. Of the deaths, two were due to malignant disease and one resulted from cerebral hemorrhage. The other 10 children died of confirmed or suspected infections. Treatment options of FA are discussed.

Transient dyserythropoiesis occurring during the involutionary phase of stage IV-S neuroblastoma.

An acutely ill 6-month-old female infant presented with massive hepatomegaly, accompanied by severe anemia with peripheral normoblastemia and thrombocytopenia. Bone marrow examination revealed erythroid hyperplasia with gross erythroid dysplasia, reduced granulocytic precursors, and virtually absent megakaryocytes. The bone marrow also contained completely necrotic cells occurring in clumps as well as singly. The appearances suggested bone marrow involvement by neuroblastoma. Accordingly, combination chemotherapy was instituted and laparotomy was performed as soon as her clinical condition had improved. Left adrenalectomy was carried out, because a small adrenal nodule of ganglioneuroma was present. Liver biopsy showed expansion of portal tracts by loose fibrous connective tissue containing hemosiderin deposits and some degenerate cellular debris, consistent with areas of involuted metastatic neuroblastoma. Complete recovery followed, and subsequent bone marrow examination was entirely normal. It is thought that the dyserythropoiesis probably resulted from the release of toxic metabolites from regressing neuroblastoma.

Haemolytic anaemia due to erythrocyte pyrimidine 5'-nucleotidase deficiency. Report of the first South African family.

The first South African case of haemolytic anaemia due to erythrocyte pyrimidine 5'-nucleotidase deficiency is reported. The anaemia is characterized by the presence of high erythrocyte pyrimidine nucleotide levels and marked basophilic stippling. The enzyme levels in 20 family members confirm an autosomal recessive mode of inheritance and illustrate the difficulty of diagnosing the carrier state.

Haemoglobin E variants: a clinical, haematological and biosynthetic study of 4 South African families.

The clinical, haematological and biosynthetic features of subjects with Hb E variants are described. An association with red cell hypochromia and microcytosis was confirmed, although this was not invariable in Hb E trait. Imbalanced globin chain synthesis was found in the majority of Hb E carriers. A patient doubly heterozygous for Hb E and Hb S, a condition we have not previously seen reported, had a benign clinical course with minor haematological changes, despite a relatively large amount of Hb S (67%).