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Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in long-term remission, but occasionally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 10 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a recurrence of their leukemia after 10 or more years from the time of achieving first complete remission (CR1). To prove that the relapse was a true recurrence rather than a second or secondary leukemia, DNA extracted from archived marrow smears was subjected to polymerase chain reaction (PCR) analysis for the presence of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful. A further program of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of childhood ALL after 10 years in remission appears to be small (around 1%), it persists. This raises questions about how blasts can survive quiescent for so long and when we can truly be confident of cure, if ever.

A study was carried out to determine the frequency of combined iron deficiency and beta-thalassaemia trait in a cohort of British Asian children to see whether the trait protects iron status. Of 470 consecutive children with red cell microcytosis, 77 had beta-thalassaemia trait and 26 (34%) of these also had evidence of iron deficiency. It was most common and profound in children under five years of age where the prevalence was 16 in 33 (48.5%). This suggests that iron deficiency is no less common in Asian children with beta-thalassaemia trait than in those without. It should not be presumed that the trait protects iron status or that the two are in any way mutually exclusive, at least in the early years.

A UK survey was carried out to discover the frequency, circumstances, and outcome of intracranial haemorrhage (ICH) complicating idiopathic thrombocytopenic purpura (ITP) of childhood. A questionnaire was circulated through the membership of the UK Paediatric Haematology Forum, and thence to local paediatricians and haematologists. It sought information on any child with ITP who had had an ICH during the 20 year period to January 1994. Fourteen instances were discovered, seven before 1984 and seven after. Six children survived the event with minimal or no sequelae, four without craniotomy. An immediately precipitating cause was noted in four; two had arteriovenous malformations and two suffered head injuries. The event occurred over two weeks from diagnosis in seven cases and over two months in five. All children were profoundly thrombocytopenic at the time of their intracranial bleed. By calculation the 14 children would have represented some 0.1% of the total with ITP during the period under review. ICH in childhood ITP may have a precipitating cause and is not necessarily fatal. There is no period of maximum risk, and it can occur at any time during the course of the illness when the platelet count is less than 10-15 x 10(9)/l. It is an extremely rare event and previous estimates of its incidence may have been too high.

To estimate the incidence and causes of secondary thrombocytosis in children, a 12 month study of all patients attending a children's hospital and discovered to have a platelet count over two times the upper normal limit (> 800 x 10(9)/l) was undertaken. Data so obtained were analysed both separately and together with those from two previous studies to gain as broad a perspective as possible. Of 7916 children who had platelet counts during the study period, 36 (0.5%) produced a value > 800 x 10(9)/l; there were 19 boys and 17 girls. There was a preponderance of young infants (median age 13 months). Twenty seven of the 36 had some sort of associated infection, bacterial in 18 and viral in nine. The other nine were either recovering from anti-neoplastic chemotherapy (n = 6), were post-operative (n = 2), or simply iron deficient (n = 1). Combining these patients with those described in previous studies allowed a review of 139 unselected children with very high platelet counts. Fifty three (38%) had infections, 29 (20%) had traumatic or surgical tissue damage, 16 (11%) had malignant disease undergoing chemotherapy or surgery, and 13 (9%) had connective tissue or autoimmune disorders. Secondary thrombocytosis is not rare and is most frequently seen in very young infants after infection. It can arise in a wide variety of other circumstances including rebound from myelosuppression, iron lack, or as part of an acute phase response. It is clinically unimportant in terms of morbidity and requires no treatment other than that for the primary condition.

Of 53 children with lymphoblastic leukaemia in their first remission who reached the fourth year after stopping treatment, 4 have subsequently relapsed and their cases are described. All are boys and 3 were over 10 at diagnosis despite there being only 6 such patients in the group overall. This suggests that teenage males are at special risk of late relapse and should not be considered cured on criteria applicable to younger females.

Consecutive children suffering from pre-B lymphoblastic leukaemia (pre-B ALL) were compared with those who had 'common' ALL (C-ALL) to assess any clinical and pathological differences between the two groups. Over 101 months 27 pre-B children were seen-an incidence in the population served of around 0.8/100,000 per year. There was some time-clustering and 12 of the 27 presented in one year (1987). The 51 patients with C-ALL who presented for comparison were distributed more evenly over the study period. Pre-B children had more basophilic blast cells with less periodic acid-Schiff positivity. They had higher presenting white cell counts and serum concentrations of lactic dehydrogenase; two variables which were correlated with each other. There was a trend towards pre-B children being younger and fewer had hyperdiploid blasts, but these differences were not statistically significant. No difference from 'common' ALL in response to therapy was apparent for the pre-B patients at a median follow up time of 17 months--too short a period for any conclusion to be drawn. Other than immunophenotype, pre-B ALL has no pathognomonic features, but there are differences from C-ALL in the distribution of some disease characteristics known to be associated with a worse prognosis.