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Biomedical subjects

J S Lilleyman

Publications and source records attributed to J S Lilleyman.

At least 19 recordsLinked to original sources
PubMed1992

Childhood polyclonal T cell lymphocytosis with neutropenia: effects of antilymphocyte globulin and granulocyte colony stimulating factor in vitro and in vivo.

The pathogenesis of the neutropenia that occurs in some patients with chronic T cell lymphocytosis is not well understood. We have investigated a 15-year-old girl with this syndrome. Initial committed bone marrow progenitor numbers (CFUgm) were low but markedly increased in vitro following T cell depletion. Similarly a transient correction of neutropenia was observed following in vivo lymphocyte depletion with antilymphocyte globulin. A sustained neutrophil recovery was achieved with daily therapy using recombinant human granulocyte colony stimulating factor (rhG-CSF) despite persistence of the lymphocytosis; during successful therapy CFUgm numbers remained low, and were not increased by the in vitro addition of rhG-CSF. These observations suggest the possibility of an inhibitory regulatory mechanism specifically acting on neutrophil granulopoiesis.

Adolescent↗
PubMed1992

Cytomorphology of childhood lymphoblastic leukaemia: a prospective study of 2000 patients. United Kingdom Medical Research Council's Working Party on Childhood Leukaemia.

Blast cell morphology of children with lymphoblastic leukaemia (ALL) entering two national multicentre trials was prospectively reviewed by three haematologists to define the clinical importance of (a) French-American-British (FAB) classification, (b) the presence of cytoplasmic vacuoles, and (c) the presence of 'hand-mirror' cells. Of 2135 evaluable children, 1907 (89%) had FAB L1 morphology and 228 (11%) L2. (L3 patients were not eligible for the trials in question). L2 patients more frequently had residual disease 14 d after starting treatment and had a significantly inferior disease-free survival, but not if the analysis was stratified for age, sex and diagnostic white cell count (WBC). 627 (29%) had blast cells with cytoplasmic vacuoles, and showed a significant survival advantage over the remainder. Vacuoles were positively associated with a low WBC, age range 1-6 years and blast cell positivity for CD10, but their benign influence was apparent even when these variables were taken into account. 'Hand-mirror' (HM) cells were only studied in UKALL X, and were noted in 316/1402 (23%) children. There appeared to be an inverse correlation between HM cells and cytoplasmic vacuoles and a weak association with T-cell immunophenotype, but no prognostic significance was evident. FAB classification appears to be of less prognostic importance than has previously been supposed, though L2 disease is more resistant to current remission induction regimens. Hand-mirror cells may be more common in T-ALL, but are seen in all types and are not related to prognosis. Cytoplasmic vacuoles are predictive of a good response to current therapeutic schedules even allowing for other prognostic variables, and are the single most important morphological feature relating to prognosis in childhood ALL.

Adolescent↗
PubMed1992

Children under two years treated according to the Medical Research Council UKALL VIII study and trial 1980-1984 (on behalf of the Medical Research Council Working Party on Leukaemia in Childhood).

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Pathology in Europe.

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Cost-Benefit Analysis↗
PubMed1991

Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood).

During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL. Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar. Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year. The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Importance of 6-mercaptopurine dose in lymphoblastic leukaemia.

To explore the possibility that higher total dosage of 'maintenance' treatment may have contributed to the recent improvement in outlook of children in the United Kingdom with lymphoblastic leukaemia, details of the amount of 6-mercaptopurine prescribed during the first two years of treatment were studied in an unselected cohort of children diagnosed between 1973 and 1987. Eighty five patients were studied, 30 diagnosed before and 55 after 1980. The group diagnosed after 1980 showed an 18% improvement in relapse free survival at five years. Their median total dose of 6-mercaptopurine had increased by 22%, whereas according to the protocol it should have risen by an average of only 9%. After 1980 boys were prescribed significantly more 6-mercaptopurine than girls, and had fewer dose reductions because of myelosuppression. These findings support the clinical impression that after 1980 an important therapeutic difference resulting from the new United Kingdom acute lymphoblastic leukaemia protocols was an increase in the amount of 6-mercaptopurine that children actually received as a result of changes in prescribing guidelines rather than dose. They also provide further evidence that boys tolerate 6-mercaptopurine better than girls, which may be related to the still unexplained difference in prognosis between the sexes.

Child↗
PubMed1991

Chromosomes in childhood acute lymphoblastic leukaemia: karyotypic patterns in disease subtypes.

To define further the clinical importance of cytogenetic analysis in acute lymphoblastic leukaemia (ALL) a prospective study was performed on 139 unselected children. Analyses were considered adequate in 104, of whom 35 were normal and 69 had clonal abnormalities. Abnormalities were categorised according to banded chromosome analysis as well as chromosome count. Karyotypes were correlated with clinical and laboratory features at diagnosis and with survival. Of the successful analyses, thirty five (34%) children had no abnormalities; this group contained an excess of T cell disease. Twenty five (24%) had a "characteristic" hyperdiploid karyotype and as a group had lower presenting white counts, a tendency to CD10, and periodic acid schiff positivity of the blast cells and smaller spleens. None was an infant and only one was over 10 years old. Seven (7%) children with t(9; 22), t(8; 14), or t(4; 11) translocations were grouped together as "specific" translocations. Collectively they had a significantly worse prognosis than the remainder. Nine children developed central nervous system relapse, six of whom had either t(4; 11) or abnormalities of 9p or 19p. A descriptive classification taking into account chromosome bonding pattern is cytogenetically more appropriate and may be more clinically useful than grouping children simply by chromosome number. As knowledge and techniques improve, the classification of cytogenetic abnormalities in ALL will need to be kept under frequent review.

Bone Marrow↗
PubMed1990

Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia.

6-mercaptopurine (6-MP) can be inactivated by S-methylation, which is catalysed by thiopurine methyltransferase (TPMT). An alternative metabolic route leads to the formation of cytotoxic 6-thioguanine nucleotides (6-TGN). To investigate whether these two pathways compete with each other to affect the therapeutic response to 6-MP, 6-TGN concentrations and TPMT enzymatic activity were measured in erythrocytes (RBC) from 95 children on long-term 6-MP therapy for lymphoblastic leukaemia (ALL). RBC TPMT activities were also measured in 130 control children and 104 long-term survivors of ALL no longer on treatment. The 95 children on 6-MP showed wide interindividual differences in RBC 6-TGN concentrations at the full protocol dose of 75 mg/m2, and RBC 6-TGN concentrations correlated negatively with RBC TPMT activity. Children with 6-TGN concentrations below the group median had higher TPMT activities and a higher subsequent relapse rate. 50 of the 104 long-term survivors had been treated with "gentle" low-dose protocols, and this subgroup contained an excess of children with lower TPMT activities compared with normal controls. These results indicate that genetically determined TPMT activity may be a substantial regulator of the cytotoxic effect of 6-MP, an effect which in turn could be important in influencing the outcome of therapy for childhood ALL.

Actuarial Analysis↗
PubMed1990

Non-randomised study comparing toxicity of Escherichia coli and Erwinia asparaginase in children with leukaemia.

Seven hundred fifty-eight unselected children entered into the United Kingdom Medical Research Council acute lymphoblastic leukaemia UKALL VIII Study and Trial were studied for differences in early treatment-related toxicity according to the type of intramuscular L-asparaginase received. Two hundred seventy-five received a product obtained from Escherichia coli and 483 the enzyme from Erwinia chrysanthemi. The E. coli patients had a significantly higher incidence of neurotoxicity, pancreatitis, and life-threatening sepsis (4%, 2%, and 20%, respectively) when compared with the Erwinia group (2%, 0%, and 18%). Severe hypersensitivity was seen in one patient from both groups and the incidence of glucose intolerance was not significantly different. These findings indicate that E. coli asparaginase may be more toxic. With a minimum follow up of 4 1/2 years there is no evidence that either product has made a significantly different contribution to disease-free survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Testicular irradiation in childhood lymphoblastic leukaemia. Medical Research Council Working Party on Leukemia in Childhoods.

The effect of randomly allocated testicular irradiation on the subsequent incidence of testicular infiltration and disease-free survival was assessed in two Medical Research Council Childhood Leukemia Trials. UKALL VI and UKALL VII. None of the 83 boys who actually received testicular radiotherapy subsequently developed gonadal disease. whereas 18 of the 163 who were not irradiated did. Despite this there is no apparent difference in disease-free survival for those randomized to receive testicular irradiation compared to those who were not, after a minimum of 8 years follow up. Although prophylactic testicular irradiation appears to prevent subsequent gonadal relapse there is no evidence that it improves overall prognosis when adequate systemic chemotherapy is used. As it has considerable long-term side effects it cannot be recommended as routine therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Factor VIII inhibitor assay using skin puncture blood samples.

A method was developed for the measurement of factor VIII inhibitors by the Bethesda technique using small volumes of skin puncture blood. Human and porcine inhibitor concentrations on paired venous and skin puncture samples measured on 10 occasions were highly correlated, with no significant difference between them. Assays on four inhibitor negative haemophiliac patients were also negative by the skin puncture method. Sample dilution at the collection stage results in loss of sensitivity to inhibitor concentrations below 1 unit/ml, but the technique will be of value in monitoring higher concentrations when venous access is difficult and must be saved for parenteral treatment.

Animals↗