264 Abstracts

pattern of disease seen in animals transplanted with leukaemic cells mimics more closely that seen in the human, and therefore responses to therapy may be a more accurate method of predicting the likely therapeutic benefit from such agents.

Treatment of Childhood Haemophagocytic Lymphohistiocytosis

D. M. Layton 1, W. Hirst 1, G. Mieli-Vergani 2, S. Strobel 3, J. Chessels 4 and J. Pritchard 4, Departments of 1Haematological Medicine and 2Child Health, King's College Hospital, London and Departments of 3Immunology and 4Haematology and Oncology, The Hospital for Sick Children, Great Ormond Street, London, UK

Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of macrophage activation occurring predominantly in childhood. Both familial (autosomal recessive) and infection related forms have been described. Between 1985 and 1990 we have treated 23 cases (male 12; female 11) of HLH. These included eight familial cases aged 3 days--15 months, defined on the basis of an affected sibling and/or history of consanguinity. The age at presentation of cases without overt genetic basis (n= 15) varied from 1 month-9.5 years. A viral trigger was identified in four cases (EBV, 2 parvovirus B 19, 1; echovirus II, 1) including one familial case. Six of eight (75%) patients, including all familial cases (n=4) who received supportive care alone died within 6 months of diagnosis. Both long term survivors in this group presented at an older age (7.5 and 8.0 years) with proven or suspected virus associated HLH. Two patients treated with corticosteroids alone died without showing a response. Thirteen cases were treated with etoposide (VP16) 150-250 mg/m 2 on days 1-3 of a 21-day cycle, in combination with methylprednisolone 1-2 mg/kg on days 1-15 (n= 12) and intrathecal methotrexate (n= 10). Nine (69%) showed a complete (n=7) or partial (n=2) response. However one patient suffered fatal cell lysis during therapy. Four (50%) of the remain- ing eight responders subsequently relapsed and died within 20 months. Of the four survivors in the group treated with VP16, three aged 2.5-9.5 years are in continuing remission after follow- up of 12-30 months. Two aged 5 and 11 months subsequently received allogeneic bone marrow transplantation (BMT). One patient underwent matched related BMT from a sibling donor.and is in complete remission at 18 months. The other who had active disease at the time of haploidentical BMT failed to engraft but, after autologous reconstitution, remains in partial remission on cyclosporin A and prednisolone at 56 months. Overall mortality was 70%, being higher in patients ~<2 years of age (15/18) compared with those >2 years (1/6) (P=0.038). The high mortality of HLH, even among cases who initially respond to VP16 and steroids, justifies a role for allogeneic bone marrow transplan- tation in selected cases with a suitable donor, particularly those with familial HLH or who are ~<2 years of age.

Accuracy of Detection of Zoster and Measles Antibodies in Paediatric Oncology Patients

J. Khan, V. A. Broadbent and J. Gray, Addenbrookes Hospital, Cambridge, UK

The case notes of 80 patients over the age of 18 months presenting to our oncology unit between 1987-1992 were reviewed for history of chickenpox and of measles vaccination. Results of complement fixation tests (CFT) at the time of diagnosis were recorded. The sera of these patients were retested using a standard commercial ELISA test detecting specific IgG.

There were 55 patients with haematological and 25 with non-haematological malignancies; 42% had a positive history of chickenpox and 94% a history of measles vaccination.

Using the CFT test, 42% of the patients with a positive history of chickenpox had detectable antibody against zoster, and 38% of the measles vaccinated patients had detectable antibody against measles.

Using the ELISA test, 97% of the patients with a positive history of chickenpox had detectable antibody against zoster, and 89% of the measles vaccinated patients had detectable antibody against measles.

There was no statistical difference between the haematological and non-haematological groups.

Comparing these two tests, the CFT had a sensitivity of 46% for zoster and 30% for measles. We conclude that the CFT test, which is still widely in use, is a poorly sensitive test for immunity and should therefore be abandoned. We found no difference in the high levels of immune antibody detected in those with a positive history of chickenpox and measles vaccination between patients with haematological and non-haematological malignancies.

Metastatic Osteoclastoma Presenting in a Child

M. S. Ashraf and F. B. Breatnach, Our Lady's Hospital for Sick Children, Dublin, Republic of Ireland

Giant cell tumours of bone are rarely seen in childhood. Presen- tation with metastases in this age group is also exceedingly rare. We report a boy who, in November 1987, presented at age 13 years 9 months with an 8-week history of right ankle pain and a 2-day history of right lower pleuritic chest pain accompanied by marked dyspnoea, nausea and weakness. Radiographic examination con- firmed the presence of multiple pulmonary and extrapulmonary metastases and a large right-sided pleural effusion. The primary tumour was in the right navicular bone. Histology of this and of a pulmonary metastasis was consistent with osteoclastoma.

A literature search at that time failed to identify any patient presenting initially with metastatic disease and there were no specific recommendations for treatment other than surgical resection. As the metastatic lesions were multiple and unresect- able we commenced treatment with chemotherapy using IVAd initially and thereafter carboplatinum/VP 16. The pleural effusion cleared and the pulmonary and extrapulmonary metastases reduced considerably in size. Chemotherapy was continued for 4 months until March 1988 and thereafter he was reviewed on a regular basis as an outpatient. The primary tumour was electively resected in November 1988. He remained well for more than 3.5 years off treatment, despite the persistence of multiple metastases which remained static in size. In November 1991 he became symptomatic with chest pain and a CT scan of the thorax showed an increase in the size of two of the metastatic lesions. These were resected in two stages. He made a good postoperative recovery and, on recent review, was well with slight further reduction of his persisting metastatic lesions.

Investigation of Treatment Related Neurotoxicity in Long Term Survivors of Childhood Cancer by Localized Proton Magnetic Resonance Spectroscopy (MRS)

A. Davidson, G. S. Payne, M. O. Leach, D. Tait, V. Ayton and R. Guy, CRC Clinical Magnetic Resonance Research Group, Royal Marsden Hospital and Institute of Cancer Research, Sutton SM2 5PT, UK

Eleven individual studies have been performed to date, on five patients and six age-matched controls. The current patient age is 11-16 years, with a median follow-up since treatment of 10 years. All had received whole brain or hemi-brain irradiation (diagnoses: four medulloblastoma, one glioma). MRS/MR imaging studies were performed, using a T2 weighted spin echo sequence in the axial plane for imaging, and stimulated echo acquisition mode (STEAM) localization for spectroscopy studies. A 2 x 3 x 3 cm volume was positioned in the paraventricular area of the fronto- parietal lobe. Metabolite signal amplitudes of choline, creatine (Cr) and N-acetylaspartate (NAA) were calculated relative to the localized water signal from the same volume, and also relative to the creatine signal.

Results suggest that all the metabolite signals in the patient group are reduced relative to tissue water, but not relative to Cr. The largest change is seen in the NAA/water ratio (mean 6.54 + 0.87), compared with age matched controls (mean 7.97 + 0.53). As NAA is found only in neurons, this is consistent with a pathological loss of neuronal tissue consequent to therapy. MRI studies showed white matter hypodensities in one patient only, but not within the volume selected for MRS. These preliminary findings suggest that proton MRS may have a role in assessment of