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It is 50 years since the first effective drug for childhood lymphoblastic leukaemia (ALL) was described. At that time the outlook for such children was certain death. Now patients have an odds-on chance of normal health and life expectancy. Although the greatest gains have been made in recent years, the classes of drug that have achieved this have all been available for over 20 years. It is their better deployment and the greater understanding of their pharmacology that have allowed both more effective protocols to be devised and long term adverse effects to be recognised and avoided. Supportive treatment has also improved in parallel. Three major problems remain: how to recognise children in whom conventional therapy will fail; how to prevent failure; and how to treat it if it occurs. Therapy will fail in some children for pharmacological reasons - noncompliance or constitutional (genetic) drug resistance. For such children in vitro drug sensitivity testing and greater pharmacological vigilance may help by identifying those at risk and allowing intervention. In others, treatment will fail because of intrinsically resistant disease that either develops despite therapy or regrows from a minimal residue. Despite wider application of sophisticated immunological and genetic studies both at diagnosis or later, recognising poor-prognosis children prospectively is hampered by the lack of a biological classification system that is sufficiently sensitive and specific to categorise all patients reliably. In those where there is no doubt about high-risk status, treatment failure rates are still unacceptably high whatever therapy is given, and salvage therapy in any child who relapses is a continuing challenge. [ABSTRACT FROM AUTHOR]

Fifty consecutive episodes of fever in neutropenic children with malignant disease or aplastic anaemia were randomized to treatment with either ceftazidime alone or a combination of azlocillin and tobramycin, pending the results of bacteriological investigation. More than 90% of organisms isolated from these episodes were sensitive to ceftazidime, which appears to be a non-toxic alternative to aminoglycosides in such circumstances. [ABSTRACT FROM PUBLISHER]

Serial measurements of enolase in the cerebrospinal fluid were made in 19 children with lymphoblastic leukaemia undergoing their first 6 weeks of antineoplastic treatment. The neurone-specific gamma enolase value rose appreciably in nearly all patients during the first two weeks of treatment, which comprised chemotherapy only, but the mean values for this isoenzyme failed to show any further rise during the subsequent cranial irradiation. In contrast the alpha enolase value, which is derived predominantly from glial tissue, rose progressively to attain its highest value during radiotherapy. A consideration of the likely rate of clearance of gamma enolase from the cerebrospinal fluid and the time sequence of administration of the several chemotherapeutic agents in UKALL VIII suggests that asparaginase may be the main causative agent in the rise of this marker of neuronal damage. [ABSTRACT FROM AUTHOR]

Liver biopsies were performed in 5 boys aged between 2 and 9 years with severe classical haemophilia who had persistently abnormal liver function tests. Abnormal histology was present in all; 4 had chronic persistent hepatitis and the fifth chronic aggressive hepatitis with early cirrhosis. Evidence of previous hepatitis B infection was present in one patient, 3 had antibodies to hepatitis, A, and 2 had subnormal levels of alpha-1-antitrypsin. Haemobilia occurred as a late complication of biopsy in one. The significance of these findings in young boys is discussed, as is the role of exposure to factor VIII containing blood products. It is concluded that cryoprecipitate should be used in preference to large pool factor VIII concentrates in children with haemophilia. [ABSTRACT FROM AUTHOR]

As part of the Medical Research Council Leukaemia Trial UKALL VIII, 738 unselected children with acute lymphoblastic leukaemia (ALL) had the morphology of their marrow blast cells reviewed by a panel of three haematologists. Ninety four (13%) showed appearances classifiable as type L2 by the French American and British (FAB) cooperative group's criteria, five (0.7%) were typed L3, and the remaining 639 (86%) as L1. Disregarding the patients classified as L3, those with the L2 variant showed an inferior disease free survival to that of the remainder (p less than 0.01), and more of them failed to remit after receiving "standard" remission induction treatment (p less than 0.01). They included an excess of older children (p less than 0.01) with less profound marrow failure at diagnosis, and fewer of them expressed the common ALL antigen (p = 0.05). There was no association between L2 morphology and the diagnostic white cell count, sex, or the presence of a mediastinal mass. These findings confirm earlier reports that FAB L2 ALL is associated with a poor prognosis and that it occurs more commonly in older children. The high remission failure rate is a recent observation and indicates that alternative early treatment may be appropriate for such patients. [ABSTRACT FROM PUBLISHER]

Mouse erythrocyte (M) rosette formation and colchicine sensitivity were compared for their ability to differentiate chronic lymphocytic leukaemia (CLL) from B cell non-Hodgkin's lymphoma (NHL) with overspill. Twenty-two cases of CLL and eight of NHL were studied along with 31 normal adults. Results from the patients in both tests differed significantly from the controls but colchicine sensitivity failed to differentiate them further. M Rosettes, on the other hand, while increased in some patients with NHL were, without overlap, much more numerous in those with CLL, and clearly distinguished the two conditions. A significant autolymphocytotoxic effect of plasma from both study groups was also noted which was not found in the controls. [ABSTRACT FROM PUBLISHER]

A semiquantitative assessment of blast cell acid phosphatase activity, expressed as a score, was made in 41 unselected children with newly diagnosed and untreated non-T acute lymphoblastic leukaemia (ALL). Despite a wide range of enzyme activity in both sexes boys had significantly higher scores than girls, and, in view of the known association between males and T ALL on the one hand, and between acid phosphatase and T ALL on the other, these findings raise the possibility that boys may have a predisposition to a type of pre-T ALL which could contribute to the as yet unexplained difference in prognosis between the sexes. [ABSTRACT FROM PUBLISHER]

Diagnostic bone marrow smears from 132 patients with acute lymphoblastic leukaemia, (ALL) were stained simultaneously by the periodic acid-Schiff (PAS) reaction, and the blast cell positivity was assessed quantitatively. The patients fell naturally into two unequal groups: those with more than 20% PAS-positive blast cells (44 patients) and those with less (88 patients). There was no relation between the degree of positivity and age, sex, or presenting leucocyte count. Actuarial survival studies showed that the group with more than 20% PAS-positive blast cells survived longer, but that this difference assumed statistical significance only after the exclusion of patients over 14 years old and those with high white cell counts at the time of diagnosis. It appears that the PAS reaction can identify long survivors among patients with ALL, but not in the absence of features strongly associated with a poor prognosis. [ABSTRACT FROM PUBLISHER]

Children from the UKALL V trial were studied to assess the clinical importance of myelosuppression during uninterrupted 'maintenance' treatment of 'standard risk' lymphoblastic leukaemia. Those receiving daily 6-mercaptopurine and weekly methotrexate who were in first remission 20 months from diagnosis were divided into two groups on the basis of whether or not they had ever had an absolute neutrophil count of less than 0.5 x 10(9)/l recorded during maintenance treatment up to that time. Of 105 evaluable children, 45 (43%) became neutropenic at least once, and 60 (57%) did not. Seven (16%) of the neutropenic group subsequently relapsed compared with 27 (45%) of the remainder. This difference was still significant if the analysis was stratified by total treatment time (two or three years), age, sex, or diagnostic white cell count. Seven (16%) neutropenic children died in remission, compared with one (2%) of the non-neutropenic children. Therapeutic myelosuppression during standard maintenance treatment of 'standard risk' lymphoblastic leukaemia is associated with increased toxicity but a reduced risk of relapse. The unexplained improvement in long term survival in the United Kingdom in recent years may in large part be due to this. [ABSTRACT FROM AUTHOR]

A prospective randomised double blind crossover trial was conducted comparing the new synthetic cannabinoid nabilone with oral domperidone in a group of children receiving repeated identical courses of emetogenic chemotherapy for a variety of malignant diseases. Eighteen of 23 consecutive eligible children, aged 10 months to 17 years, completed the trial. When taking nabilone they experienced significantly fewer vomiting episodes and less nausea, and two thirds expressed a preference for the drug. The most common side effects of treatment with nabilone were somnolence and dizziness, with one patient being disturbed by hallucinations. The results indicate that nabilone is an effective antiemetic for children having chemotherapy, even for young children. It seems to be superior in this respect to domperidone, and although it has a higher incidence of side effects, these are mostly acceptable to patients. It can be recommended as an alternative to conventional antiemetic treatment throughout childhood. [ABSTRACT FROM AUTHOR]