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J Lilleyman

Publications and source records attributed to J Lilleyman.

10 recordsLinked to original sources
PubMed2005

Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial.

Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event-free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0.0007). Event-free survival was significantly improved with dexamethasone (84.2% vs. 75.6% at 5 years; P = 0.01), with no evidence of differing effects in any subgroup of patients. The use of 6.5 mg/m(2) dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk-groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.

Adolescent↗
PubMed2000

Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. UK Medical Research Council's Working Party on Childhood Leukaemia.

Treatment of children with acute lymphoblastic leukaemia (ALL) aims to cure all patients with as little toxicity as possible and, if possible, to restrict further intensification of chemotherapy to patients with an increased risk of relapse. However in Medical Research Council (MRC) trial UKALL X two short myeloablative blocks of intensification therapy given at weeks 5 and 20 were of benefit to children in all risk groups. The successor trials, MRC UKALL XI and MRC ALL97, tested whether further intensification would continue to benefit all patients by randomising them to receive, or not, an extended third intensification block at week 35. After a median follow-up of 4 years (range 5 months to 8 years), 5 year projected event-free survival was superior at 68% for the 894 patients allocated a third intensification compared with 60% for the 887 patients who did not receive one (odds ratio 0.75, 95% CI 0.63-0.90, 2P = 0.002). This difference was almost entirely due to a reduced incidence of bone marrow relapses in the third intensification arm (140 of 891 in the third intensification arm vs. 171 of 883 in the no third intensification, 2P = 0.02). Subgroup analysis suggests benefit of the third intensification for all risk categories. Overall survival to date is no different in the two arms, indicating that a greater proportion of those not receiving a third intensification arm and subsequently relapsing can be salvaged. These results indicate that there is benefit of additional intensification for all risk subgroups of childhood ALL.

Adolescent↗
PubMed1998

Late relapsing childhood lymphoblastic leukemia.

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.

Adult↗
PubMed1997

The relationship between laparoscopic disease, pelvic pain and infertility; an unbiased assessment.

OBJECTIVES: To measure the relationship between laparoscopically detected pelvic pathology and pelvic pain or infertility. METHODS: Women undergoing diagnostic laparoscopy either for the investigation of pelvic pain, for sterilisation or for the investigation of infertility were studied. The indication for surgery was recorded before laparoscopy. At operation a series of 35-mm slide photographs were taken of the pelvis and later scored by two independent assessors without knowledge of the indication for surgery. RESULTS: Satisfactory photographs were obtained in 298 women. Minimal endometriosis was not associated with pain (adjusted OR 1.3; 0.5-2.8), although moderate disease was non-significantly so (2.5; 0.4-7.1). Severe disease was significantly more common and never occurred in patients being sterilised (P = 0.02). The odds of pain were not increased in the presence of dilated veins > 9 mm diameter (OR 1.1; 0.4-3.2) or adhesions (OR 0.6; 0.2-4.7). The odds of infertility were non-significantly increased in the presence of minimal and moderate endometriosis (OR 2.0; 0.8-5.3, and OR 4.2; 0.6-25 respectively) and again significantly more common in the presence of advanced disease (P = 0.002). The odds of infertility tended to be lower in the presence of severely dilated veins (OR 0.2; 0.032-1.2). There was no clear effect of adhesions (OR 0.9; 0.1-5.9). CONCLUSIONS: The long established associations between severe endometriosis and pelvic pain, and between endometriosis in general and infertility are confirmed. However there is little or no association between minimal endometriosis, pelvic adhesions or dilated pelvic veins and pain. Previously reported associations may have been an artefact of the surgeon's knowledge of the indication for operation when assessing the pelvis.

Endometriosis↗
PubMed1987

Medical Research Council Childhood Leukaemia Trial VIII compared with trials II-VII: lessons for future management.

This improvement in medium disease-free survival is probably a result of sustained early cell kill, and UKALL VIII has enabled us to define risk categories requiring even further continuous intensification, as now introduced in MRC UKALL X. Thanks to the greater availability of blood products, for example, the rational use of antibiotics and the development of expertise amongst nurses and doctors, such sustained therapy can now be delivered on a multi-centre basis, but only in experienced centres. The monitoring and removal of morbidity are essential if the advantages of this more sustained chemotherapy are to be realised. All elements of therapy require controlling and patients, parents and, above all, doctors must comply with protocol requirements in order to build further upon these initial promising results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Chemotherapy of childhood lymphoblastic leukaemia: the first 50 years.

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: (i) how to recognise children in whom conventional therapy will fail; (ii) how to prevent failure; and (iii) 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.

Antineoplastic Agents↗