O. B. Eden

Recognition of abnormal lysosomal enzyme patterns in childhood leukaemia by isoelectric focusing, with special reference to some properties of abnormally expressed components.

Abstract Isoelectric focusing profiles of six lysosomal enzymes, β-hexosaminidase, α-fucosidase, α-mannosidase, β-glucuronidase, acid phosphatase and α-galactosidase, were studied in lymphoid cells derived from childhood leukaemic patients and control subjects. Altered β-hexosaminidase patterns were observed in nine out of eleven patients with common ALL, in one patient with null-cell ALL and two with acute undifferentiated leukaemia. These changes were not confined to β-hexosaminidase, for other enzymes including α-fucosidase, α-mannosidase, β-glucuronidase and acid phosphatase were commonly involved. Altered enzyme patterns returned to normal with remission. With the exception of acid phosphatase abnormally expressed enzymes appeared to represent more anodic forms of the parent enzymes. For β-hexosaminidase the leukaemic enzymes unlike the normal forms were found to be neuraminidase-sensitive whereas other properties of the enzymes were found to be similar to their native forms. It is suggested that studies on lysosomal enzymes may be valuable in the differentiation of sub-types of leukaemia.

ACUTE LYMPHOBLASTIC LEUKEMIA AND KLINEFELTER'S SYNDROME

We report two children with acute lymphoblastic leukemia (ALL) who in initial cytogenetic investigation were coincidently found to have a 47, XXY karyotype. In one patient 100% of peripheral blood lymphocytes showed a 47,XXY complement, but in the other only 30% of cells had such a complement, the remainder having a normal male karyotype (46, XY). In neither case was the diagnosis of Klinefelters syndrome clinically obvious. Antileukemic therapy may exacerbate both the hypogonadism and the learning difficulties seen in this condition. Routine cytogenetic investigations on peripheral blood and bone marrow should be performed in all new cases of leukemia. Cytogenetic analysis of cultured fibroblasts is essential in all cases in which the abnormal X line did not disappear after initial therapy. Evidence of an increased risk of leukemia in association with Klinefelters is beginning to accumulate.

Improved survival for childhood acute lymphoblastic leukemia: possible effect of protocol compliance.

Survival rates were analyzed for an effectively population-based series of 77 children with acute lymphoblastic leukemia treated at one hospital during 1970-1981. Treatment was according to Medical Research Council protocols UKALL I to UKALL VII but with a great emphasis on compliance. The relapse-free survival rate was 54.5% at 5 years. The overall 5-year survival rate of 64% was substantially higher than the 47% recorded during a similar period over the rest of Britain. The difference between survival rates in this series and nationally was especially marked for children aged 2-9 years (76% versus 50%) and with white blood count under 10 x 10(9)/L (87% versus 57%). For both of these groups, the survival rates achieved were similar to those now being recorded for the UKALL VIII trial in which treatment is more sustained than in its predecessors and there is greater emphasis on doctor compliance with protocol. These results suggest that although the advantage of UKALL VIII over previous trials for poor prognosis patients may be attributed to the more sustained treatment, the improvement for good prognosis patients may be due to more rigorous compliance with protocol.

Serological study of Pneumocystis carinii infection in the absence of immunosuppression.

Serum samples from 145 children with no known immunosuppressive illness were examined by indirect immunofluorescence for antibody to Pneumocystis carinii. Positive antibody titres (greater than or equal to 1:8 dilution) were found in 69 children (48%). Antibody could not be detected in the remaining children. Previous studies have shown that at least 75% of children have antibodies to P. carinii by the age of 4 years. This study shows a lower percentage of children with detectable antibody. This may be related to geographical variation of antigen or possibly to the widespread use of co-trimoxazole.

Is there a danger in delaying radiotherapy in childhood medulloblastoma

Approximately 45-50% of children with medulloblastoma are cured by conventional surgery and radiotherapy, but survivors may face severe late neuropsychological toxicity. Studies showing good partial responses to platinum-based chemotherapy in relapsed patients and the theoretical possibility of a therapeutic window immediately after surgery have prompted neoadjuvant treatment studies which are ongoing. However, the absolute benefit of chemotherapy for the treatment of medulloblastoma in childhood is, as yet, not proven. There is a danger that chemotherapy may simply delay radiotherapy, and in so doing reduce the radiological impact of this known effective treatment. We report four children with medulloblastoma presenting consecutively to this unit over a 6-month period, whose management was problematic because of either failure to respond to neoadjuvant chemotherapy or their very young age. These cases are discussed in the light of the current literature and future treatment strategies that must seek to improve the therapeutic ratio of multimodality therapy.

Imaging and treatment of disseminated neuroblastoma with 131I-metaiodobenzylguanidine

A 7-year-old girl presented in August 1983 with a 4-month history of diffuse limb pains, loss of weight and general malaise. The pain had commenced in the neck and progressed to involve the right shoulder, both legs and spine. Examination revealed two firm right-sided cervical lymph nodes, 1 cm in diameter, and some smaller, firm nodes palpable over the occiput and in the inguinal regions. There was diffuse abdominal tenderness in the left upper quadrant but no other abnormal findings. Initial investigation showed a haemoglobin level of 7.9 g/dl (normochromic film), white cell count 5.9 x 109/1, ESR 90 mm in 1 h. Twenty-four-hour assay of 4-hydroxy-3-methoxymandolate was increased above 30 μmol/24 h (normal laboratory range < 30 μmol). Metadrenalin assay was 3.7/μmol/24h (normal laboratory range up to 7 μmol). Cystathionine was not detected in the urine. Chest radiography showed an enlarged left hilum associated with extensive paravertebral widening, and abdominal radiography showed calcification in the r...

Variations in incidence of childhood leukaemia in South East Scotland (1970–1984)

Concern has been expressed recently about apparent increases in the incidence of leukaemia amongst young people living in certain geographical areas. We analysed the incidence of childhood leukaemia in South-East Scotland (excluding North-East Fife) from 1970 to 1984. There was a significant geographical variation in incidence of ALL with an excess in Fife concentrated in a small area of one district partly balanced by a relative decrease in Edinburgh. We feel that the variation is unlikely to be an artefact of geographically biased mis-diagnosis.

Scottish validation study of cancer registration data childhood leukaemia 1968–1981—I

This study attempted to validate central registration data on all childhood leukaemia cases in Scotland between 1968 and 1981 in line with the Black Enquiry concerning West Cumbria. Missing files precluded a complete verification, but minor errors of registration were found in 44% of cases. A small number of important mistakes of omission (eight cases), wrong diagnosis (six cases) and postal code errors (nine cases) were found which might affect epidemiological studies of these relatively rare diseases. Precise and verified prospective data collection at the time of diagnosis is essential if the spatial distribution of childhood cancers is being studied.

Skin rash after completion of therapy for leukemia in childhood

The medical records of 58 patients who were surviving after completing treatment for acute lymphoblastic leukemia were reviewed to determine the incidence of skin rash occurring after their treatment had ended. Twenty-eight (48%) developed a rash within 3 months of completing treatment. In the majority this was erythematous, affected the face, and in all patients was transient. There was an increased incidence of rash in those patients who had eczema or asthma or who had a family history of eczema or asthma. It would seem prudent to warn parents of this phenomenon and reassure them of its benign nature.

Hemophagocytosis and Acute Monoblastic Leukemia

A 16-month-old girl presented with hepatosplenomegaly and pancytopenia. Bone marrow aspiration showed a florid increase in macrophages with marked hemophagocytosis. She subsequently improved spontaneously with no therapeutic intervention, but 2 months later presented with frank acute monoblastic leukemia. This case illustrates the difficulties in classifying malignancies of the monocyte-macrophage lineage and how hemophagocytosis can be the presenting feature of a range of diseases.