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The formation of intracellular thionucleotides are a prerequisite for mercaptopurine (MP) cytotoxicity, and interindividual variations in the inherited level of thiopurine methyltransferase (TPMT) activity regulate their formation. Measurement of pretreatment TPMT activities can identify the TPMT "deficient" patient and, conversely, the individual with very high enzyme activities. The former are at higher risk of acute toxicity and potentially fatal bone marrow failure and the latter of suboptimal treatment. Leukaemic children taking MP therapy who form inadequate amounts of thioguanine nucleotides (TGNs) do not experience drug toxicity and are at an increased risk of disease relapse. When low TGNs are due to very high TPMT activities, thioguanine may be a more appropriate thiopurine. Another cause of inadequate TGN concentrations is partial or noncompliance with oral chemotherapy. Compliance problems can be identified by the measurement of both TGNs and methylated drug metabolites.

1. Red blood cells from four children with lymphoblastic leukemia were age fractionated on Percoll density gradients into 'young', 'middle-aged' and 'old' cells. 2. The rates of accumulation of the mercaptopurine (MP) metabolites thioguanine nucleotides (TGNs) and methylmercaptopurine nucleotides (MeMPs) were measured in the cell fractions from the start of MP continuing chemotherapy. 3. TGNs and MeMP metabolites were present in all the red cell fractions after 3 days oral MP. There was no significant difference between the metabolite concentrations measured in either young, middle-aged or old cells (Mann-Whitney P = 1.0 to 0.12). 4. These observations suggest that MP metabolites do not enter red cells at the stem cell level at the start of therapy. 5. With respect to the monitoring of therapy, these results suggest that the concentration of TGNs after 7 to 10 days MP could be used to predict eventual steady-state concentrations using a simple model.

Ten per cent of children entered into the national leukaemia study UKALL VIII were under 2 years at diagnosis. The 6 year event-free survival of this cohort was 39%. Specific adverse features were age under 1 year, high initial white cell count and null cell ALL. Those with common ALL, WBC 10-50 x 10(9) 1-1 and especially those aged 18 months or older did not have an adverse prognosis compared with the whole trial entrants. Overall, however there was a doubling of CNS relapse rate and of both induction and remission deaths. Those with a WBC under 10 x 10(9) 1-1 had a high haematological relapse rate. The type of leukaemia and method of management rather than specifically the age appeared to be the predictor for poor outcome.

Six patients with various forms of leukaemia had neurological signs and symptoms associated with an extremely high white blood cell count and increased whole blood (but not plasma) viscosity. All were treated by leucapheresis with an Aminco Celltrifuge. Rapid and complete reversal of all symptoms occurred in three patients and partial recovery in one. One patient died shortly after leucapheresis and another (from cerebral intravascular coagulation) two days later. It is concluded that a cellular hyperviscosity syndrome may cause neurological dysfunction in patients with extremely high white cell counts, and that leucapheresis, in carefully selected patients, can be an effective method of treatment.

Of 46 adult patients with active leukaemia whose white cells were examined using a Hemalog D automated differential leucocyte counter, 45 showed abnormalities indicative of their disease, and the odd one out would not have been missed due to associated thrombocytopenia. Sequential studies while on chemotherapy allowed rapid and accurate neutrophil counts to be performed even in the presence of profound leucopenia and the re-emergence of blast cells in some cases was detected 2--3 weeks earlier than by microscopy. These findings indicate that the Hemalog D is reliable in the detection and can be useful in the follow-up of patients with leukaemia.

Two children are described with acute leukemia in remission who both developed a swinging pyrexia and pathologically identical splenic necrotizing granulomata. No organisms were seen in, or isolated from, either spleen. After splenectomy, systemic symptoms persisted and did not resolve until steroids were given. The etiology of this syndrome remains unknown.

Unequivocal lymphoblastic leukaemia in a 4-year-old boy was followed 3 years later by equally unequivocal myeloblastic leukaemia in his 20-year-old brother. The boy achieved complete remission and remains well more than 6 years later whereas his brother failed to respond to treatment and died after 5 months. The parents and 3 remaining siblings showed no recognized features suggesting a constitutional predisposition to leukaemia despite thorough investigation.