P. H. Morris Jones

TESTICULAR HISTOLOGY AFTER COMBINATION CHEMOTHERAPY IN CHILDHOOD FOR ACUTE LYMPHOBLASTIC LEUKÆMIA

A study of testicular histology has been made in 44 boys treated with combination chemotherapy for acute lymphoblastic leukaemia. At the time of testicular biopsy 21 boys were still receiving cytotoxic drugs and 23 had completed their chemotherapy some time earlier. Evidence of leukaemic infiltration was seen in 5 (11%), interstitial fibrosis in 24 (55%), and basement-membrane thickening in 6 (14%). The mean tubular fertility index in the 44 biopsies was 50% of that in age-matched controls, and 18 of the biopsies had a severely depressed tubular fertility index (40% or less). Three variables had a highly significant effect on the tubular fertility index: previous therapy with cyclophosphamide or cytosine arabinoside (greater than 1 g/m2) depressed the tubular fertility index, whereas with increasing time after completion of chemotherapy the tubular fertility index improved. The prognosis for fertility in these subjects is not known. Long-term surveilance is necessary.

Residual disabilities in children treated for intracranial space‐occupying lesions

A retrospective study of 30 long‐term survivors of cranial or craniospinal irradiation for intracranial space‐occupying lesions has demonstrated physical and mental handicaps in the majority. This is most severe in those cases treated before the age of 11 years, and is not confined to those children having craniospinal or whole‐brain irradiation. The mental handicap also appears to be progressive, but cannot be easily examined in this retrospective study.

The treatment of Wilms' tumour: results of the United Kingdom Children's cancer study group (UKCCSG) second Wilms' tumour study.

The aims of the UKW2 study were: (1) to further refine treatment for stage I and II favourable histology (FH) patients; (2) to consolidate the UKW1 results for stage III FH patients; (3) to improve the outlook for patients with inoperable primary tumours and those patients with stage IV and unfavourable histology disease. Treatment consisted of primary nephrectomy, wherever possible, followed by chemotherapy and radiotherapy, as dictated by stage and histology. Treatment was refined successfully for stage I and II FH patients. The 4-year event-free survival for these two groups was 94% and 91%, respectively. Stage III FH patients had a 4-year event free survival of 84%. The outlook for patients with clear cell sarcoma of the kidney is as good as for patients with favourable histology, whilst that for patients with anaplastic or rhabdoid variants remains poor. The outlook for the majority of children with Wilms’ tumour is now excellent.

Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens

Eight children treated between 1977 and 1983 with the UK Childrens Cancer Study Groups non-Hodgkin lymphoma (NHL) and T-cell protocols have developed second malignancies within 7 years of commencing treatment. Five developed acute non-lymphoblastic leukaemia and a sixth died from infection while pancytopenic with a pre-leukaemic marrow. The other malignancies were cerebral astrocytoma and an undifferentiated low grade sarcoma. These eight children were included among 261 children studied in the first UKCCSG NHL and T-cell trials giving an actuarial incidence of 7.8% second malignancy at 7 years. Six had received adjuvant radiotherapy which may have contributed to the high incidence of second malignancy.

Relationship between the pretreatment proliferative activity of marrow blast cells and prognosis of acute lymphoblastic leukaemia of childhood.

Pretreatment marrow blast cells were studied in 38 boys and 27 girls (aged 1-14) with acute lymphoblastic leukaemia by flow cytometry after staining with propidium iodide.The percentage of blast cells in the S phase of the cell cycle ranged from 1% to 40% (median 6%). A correlation was found between the percentage of cells in S and the morphological classification of the French American British Cooperative Group (FAB), presence of T or B cell markers, haemoglobin concentration, blast size, bone pain, platelet count, and an inverse correlation with coarse granule and block staining with Periodic-acid-Schiff (PAS).63 of the 65 children attained complete remission. During the first 24 months of follow up there were fewer relapses (P = 0·054), and deaths (P = 0·004) in those children with 6% or fewer blasts in S phase. The difference was most marked in the first 12 months with 4 relapses out of 33 in the group with 6% or fewer cells in S compared with 13/30 in the group with > 6% cells in S.In order to investigate the prognostic significance of the pretreatment proliferative studies in greater detail, remission duration was correlated with 17 presenting features. Each feature was correlated individually and then the simultaneous effect of all the features was assessed by stepwise multiple regression.Only 3 features of the disease at diagnosis were individually correlated with duration of remission. These were% cells in S (P < 0·001), log white cell blood count (WBC) (P < 0·01) and the presence of T- or B-cell surface markers (P < 0·05). However, the multiple regression analysis showed that cell markers were not an independent prognostic feature, whereas the percentage cells in S and log WBC were independently and significantly correlated with duration of first remission (P < 0·001 in each case).

Fatal pulmonary fibrosis following 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy.

A case is reported of a child with fatal pulmonary fibrosis following BCNU therapy. This side effect has only once previously been reported with the nitrosourea group of compounds.

Children in long-term remission after treatment for acute lymphoblastic leukaemia show persisting haemopoietic injury in clonal and long-term cultures

Twenty children who were in unmaintained full haematological remission after treatment for acute lymphoblastic leukaemia (ALL) showed a significantly lower incidence of granulocyte‐macrophage progenitor cells (GM‐CFC) in the bone marrow compared to controls. This low incidence lasted for up to at least 3 years after the cessation of chemotherapy. There was no tendency to higher values with longer times after treatment, and the low incidence was not predictive of relapse.

Hodgkin's disease complicated by the nephrotic syndrome.

A 12‐year‐old boy with nodular sclerosis Hodgkins disease demonstrated nephrotic syndrome. A renal biopsy studied with light microscopy, electron microscopy, and immunofluorescence showed minimal change glomerulonephritis and some foci of fluorescence with anti‐IgM. A literature review revealed that 35 cases of Hodgkins disease with nephrotic syndrome have been reported. Possible etiologic mechanisms are discussed.

Childhood leukaemia in North West England 1954-1977: epidemiology, incidence and survival.

The annual incidence of leukaemia among children aged up to 14 years as estimated by the Manchester Childrens Tumour Registry has been analysed for the 24 years 1954-1977. A significant increase in acute lymphoid leukaemia (ALL) was found, while the incidence of acute myeloid leukaemia (AML) remained constant. Other types of leukaemia were too rare to be analysed separately. The increase in ALL was concentrated among boys in the 1--5-year age group. Analysis with respect to initial white-cell count showed the increase to be more pronounced in children with initial white cell counts of 1-5 x 10(4)/microliters. The proportion of cases presenting in Lancashire compared with Greater Manchester did not change during the study period. The distribution of cases with respect to social class and socio-economic group of the parents also remained constant. Due to advances in the treatment of childhood ALL survival improved considerably during the study period and no increase in mortality was seen.

Neuroblastoma-When are urinary catecholamines and their metabolites 'Normal'?

The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.