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Biomedical subjects

H Ekert

Publications and source records attributed to H Ekert.

At least 19 recordsLinked to original sources
PubMed2001

Cost-utility analysis of recombinant factor VIIa (NovoSeven) in six children with long-standing inhibitors to factor VIII or IX.

The high cost of treating patients with inhibitors in an environment of restricted budgets warrants consideration of cost-effectiveness. We determined the clinical response, effect on quality of life and the cost-effectiveness of treatment with rFVIIa in six boys with long-standing inhibitors to factors VIII or IX, compared with other treatment regimes previously used in these patients. The study used a longitudinal before-and-after design and was conducted in three phases. Phase 1 was 6 months preceding the introduction of rFVIIa, during which patients received on-demand 'usual care' with other treatment regimes; phase 2 was 6 months treatment on rFVIIa assessed retrospectively; and phase 3 was 6 months on rfVIIa treatment assessed prospectively. Treatment with rFVIIa was reserved for intrarticular, compartment, psoas, mucosal and suspected intracranial bleeding. Treatment outcomes were obtained by interview using structured questionnaires, the quality-of-life instruments CHQ CF-80 and CHQ PF-50, patient self-reporting diary, interrogation of hospital records, and the EuroQoL EQ-5D for utility valuations. Our results confirm that rFVIIa is clinically effective and resulted in 63-92% reductions in the number of re-treatments, duration of painful episodes, delay to initiation of treatment, days requiring wheelchair or crutches, emergency room visits and lost carer time compared with the patients' other therapies. Quality-of-life improvements were observed in several important areas as perceived by both patients and their families, at an incremental cost per QALY of A$51 533.

Adolescent↗
PubMed2000

Induction of immune tolerance and suppression of anaphylaxis in a child with haemophilia B by simple plasmapheresis and antigen exposure.

Anaphylaxis to factor IX (FIX) in patients with haemophilia B is a rare and life-threatening complication that has been reported to occur in association with the development of inhibitors to FIX. Management of these patients is difficult. This report presents an 18-month-old boy with a frame-shift mutation of the FIX gene and FIX coagulant level of <1% who developed anaphylactoid reactions to low and high purity plasma-derived FIX concentration infusions and an inhibitor measuring 1.0 BU mL(-1). The patient was managed with simple plasmapheresis, a short course of corticosteroids and high-dose antigen exposure, which successfully induced long-lasting immune tolerance to FIX concentrates.

Anaphylaxis↗
PubMed2000

Cognitive and academic outcome following cranial irradiation and chemotherapy in children: a longitudinal study.

Cranial irradiation therapy (CRT) and chemotherapy are associated with neurobehavioural deficits. Many studies have investigated late effects of these treatments, but few have evaluated changes in abilities over time. This study employed a longitudinal design to map abilities following these treatments. Three groups of children were studied: Group 1 (n = 35): children treated with CRT (18 Gy) + chemotherapy, aged 5 years or less at time of diagnosis; Group 2 (n = 19): children treated with chemotherapy alone, aged 5 years or less at time of diagnosis; Group 3 (n = 35): healthy children. All children were aged 7-13 years at time of initial assessment, with no pre-diagnosis history of neurologic, developmental, or psychiatric disorder. Intellectual and educational abilities were evaluated twice: T1, not less than 2 years post-treatment, and T2, 3 years later. Group 1 achieved poorest results at T1, with comparison groups performing similarly. At T2 group differences were maintained. For verbal skills differences remained stable. Group 1 exhibited deterioration on non-verbal and processing tasks, while comparison groups showed improved abilities. Group 1 exhibited increases in literacy skills, with educational intervention predicting progress. Results suggest cumulative deficits in non-verbal and information processing skills for children treated with CRT + chemotherapy, with other deficits remaining relatively stable over time. Improved literacy skills suggest that gains can occur with remediation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

High incidence of treatment failure with vincristine, etoposide, epirubicin, and prednisolone chemotherapy with successful salvage in childhood Hodgkin disease.

BACKGROUND AND PROCEDURE: In an attempt to further reduce the long-term toxicity of chemotherapy for childhood Hodgkin disease (HD), the Australian and New Zealand Children's Cancer Study Group between 1990 and 1996 enrolled 53 children with biopsy-proven and imaging-staged HD into a chemotherapy-only treatment regimen using 5-6 courses of vincristine, etoposide, epirubicin, and prednisolone (VEEP). RESULTS: There were 23 events in these children with 3 progressive disease (PD), 8 partial remissions (PR), and 12 relapses. In the stage I patients, there were 8 events (35%). There was no association between the number of events and the stage of HD. Massive mediastinal disease at diagnosis was present in 16 patients, 11 of whom had an event with 3 PD, 3 PR, and 5 relapses. For all patients with an event at 6-24-month follow-up, all but two patients were salvaged with either alkylating agent-based chemotherapy alone or with irradiation and chemotherapy. The event-free survival for the whole group with median follow-up of 33 months was 59%, but only 31% for massive mediastinal disease. Disease-free survival was 78% and overall survival at 60 months was 92%, with one death due to drug-induced aplasia and another from acute myeloid leukemia. CONCLUSIONS: We conclude that VEEP chemotherapy in childhood HD used as the only treatment modality has an unacceptably high treatment failure rate in patients with massive mediastinal disease and 35% incidence of treatment failure in stage I disease.

Adolescent↗
PubMed1997

Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia.

The Philadelphia translocation is associated with a poor prognosis in adults and children with acute lymphoblastic leukemia, even though the majority of patients achieve remission. To test the hypothesis that the translocation leads to drug resistance in vivo, we studied 61 children and 20 adults with acute lymphoblastic leukemia and used the level of minimal residual disease at the end of induction as the measure of drug resistance in vivo. In children the presence of the translocation was associated with a significant increase in residual disease, indicating higher drug resistance in vivo; five of seven Philadelphia-positive children but only five of 54 Philadelphia-negative children had a minimal residual disease level >10(-3), a level which is associated with a high risk of relapse in childhood acute lymphoblastic leukemia of standard risk. By contrast, in adults, residual disease and hence drug resistance was already higher than in children, and the presence of the Philadelphia translocation in seven patients had no obvious additional effect. We conclude that the Philadelphia chromosome may increase resistance to drugs in vivo in children, but not detectably in adults.

Adolescent↗
PubMed1997

Cross-reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand.

BACKGROUND: Inhibitory antibodies which neutralise factor VIII develop in 10-20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross-react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross-reactivity. AIMS: To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22. METHODS: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A. RESULTS: Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients, 1-19% in six, 20-39% in 11 and 40-80% in five. In six of nine patients with acquired haemophilia cross-reactivity was < or = 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor. CONCLUSIONS: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor VIIa or prothrombin complex concentrates.

Animals↗
PubMed1996

Risk factors for intellectual and educational sequelae of cranial irradiation in childhood acute lymphoblastic leukaemia.

Long-term cognitive and educational sequelae have been inconsistently reported in children who received cranial irradiation (CRT) to prevent central nervous system (CNS) disease in acute lymphoblastic leukaemia (ALL). This study investigates a large and representative sample of survivors of ALL and compares them with non-irradiated survivors of cancer and healthy control children to determine the effect of CRT on cognitive and educational ability. Three groups of children were studied: Group 1 (n=100) survivors of ALL treated with chemotherapy and CRT, group 2 (n=50) children with a variety of malignancies treated with chemotherapy alone, group 3(n=100) healthy children. Cognitive and educational abilities of these groups were evaluated using standardised psychometric techniques. Significant differences in cognitive and educational abilities were found between the children in group 1 (chemotherapy + CRT) and the two control groups, with the children receiving CRT performing less well in a range of tests. Greatest differences were detected for tasks dependent on language function including verbal IQ, reading and spelling. Within group 1 a younger age at treatment (less than 5 years) and a higher dose of CRT (24 Gy vs 18 Gy) were predictive of poor long-term outcome for cognitive and education ability. In contrast, children who received chemotherapy alone, with or without intrathecal methotrexate, performed similarly to healthy controls. No gender differences were detected for these measures.

Adolescent↗
PubMed1996

Experience with recombinant factor VIIa in Australia and New Zealand.

Recombinant factor VIIa (rFVIIa; NovoSeventrademark) was availablefor compassionate use in Australia and New Zealand from 1991 to 1994. Over this period there were 18 treatment episodes in 9 patients, age 8-66 years, with haemophilia A and high titre inhibitors cross-reacting with porcine factor VIII. There were no significant adverse effects. Treatment with rFVIIa resulted in a successful outcome in 8 potentially life-threatening (retroperitoneal, subdural, gastro-intestinal) bleeds. Elective cystoscopy, repair of a cranial flap, yttrium synovectomy and inguinal herniotomy were performed successfully, as was surgical decompression of a flexor pollicis longus bleed. Treatment of a patient with an infected haematoma had limited success, attributed to intermittent suboptimal doses. In 2 patients, satisfactory haemostasis was achieved for multiple dental extractions; subsequent oozing was attributed to suboptimal rFVIIa and/or antifibrinolytic therapy.

Adult↗
PubMed1995

Haemophilia A management in Victorian, New South Wales and South Australian haemophilia centres.

OBJECTIVE: To examine the management of haemophilia A in Australia and to compare it with international trends. METHODS: Six haemophilia centres treating most patients in Victoria, New South Wales and South Australia were surveyed in 1993 by means of a written questionnaire followed by an "on site" interview. RESULTS: The centres were treating 739 patients; 234 (32%) had severe haemophilia. Factor VIII inhibitors were present in 5.9% of all patients and in 19% of those with severe disease. Twenty-three per cent were human immunodeficiency virus (HIV) antibody-positive and 74% were hepatitis C virus (HCV) antibody-positive. The main treatment was "on demand" therapy for acute bleeds (average use of factor VIII: 1350 IU/kg per year for children; and 780 IU/kg per year for adults). Prophylactic therapy was used in only 17 patients, with doses of 3000-4500 IU/kg per year. One million IU was used for three patients with high titre inhibitors who had "tolerising" therapy. While most developed countries have a factor VIII supply of 2-5 IU per capita, the total supplied to the States represented 1.46 IU per capita, while use at the centres represented 1.1 IU per capita. CONCLUSION: Because supply of factor VIII is limited, use was less than half that recommended internationally. Shortage of factor VIII has compromised prophylactic therapy and virtually prevented "tolerising" therapy.

Acute Disease↗
PubMed1995

Characterization of clonal immunoglobulin heavy chain and I cell receptor gamma gene rearrangements during progression of childhood acute lymphoblastic leukemia.

Instability of antigen receptor gene rearrangements during progression of acute lymphoblastic leukemia (ALL) has important implications for polymerase chain reaction (PCR)-based techniques using these genes for the detection of minimal residual disease (MRD). Antigen receptor gene instability may lead to false negative results in bone marrow samples taken during remission. Utilizing the PCR and consensus primers for rearranged immunoglobulin heavy chain (IgH) and T cell receptor gamma (TCR gamma) gene sequences, we analyzed the bone marrow samples at diagnosis and first relapse for 37 children with ALL. The incidence of clonal evolution at the IgH locus was 9/33 (27%) and at the TCR gamma locus 1/15 (7%). In four of the nine patients with clonal evolution at the IgH locus, the sequence at relapse retained the diversity and joining region (D-N-J) sequences from diagnosis. Patients with clonal evolution were characterized by a higher incidence of more than one IgH PCR band at diagnosis and by late relapse (> 18 months from diagnosis). These results suggest that, where possible, patients with more than one IgH PCR rearrangement at diagnosis should be monitored using another antigen receptor gene, such as TCR gamma, since evolution for this gene was found to be a rare event. By combining this approach with a strategy directed at the more stable D-N-J region of the IgH gene, MRD false negativity would have occurred in less than 10% of patients in the present study.

Adolescent↗
PubMed1994

Outcome prediction in childhood acute lymphoblastic leukaemia by molecular quantification of residual disease at the end of induction.

Methods to detect and quantify minimal residual disease (MRD) after chemotherapy for acute lymphoblastic leukaemia (ALL) could improve treatment by identifying patients who need more or less intensive therapy. We have used a clone-specific polymerase chain reaction to detect rearranged immunoglobulin heavy-chain gene from the leukaemic clone, and quantified the clone by limiting dilution analysis. MRD was successfully quantified, by extracting DNA from marrow slides, from 88 of 181 children with ALL, who had total leucocyte counts below 100 x 10(9)/L at presentation and were enrolled in two clinical trials, in 1980-84 and 1985-89. Leukaemia was detected in the first remission marrow of 38 patients, in amounts between 6.7 x 10(-2) and 9.9 x 10(-7) cells; 26 of these patients relapsed. Of 50 patients with no MRD detected, despite study of 522-496,000 genomes, only 6 relapsed. The association between MRD detection and outcome was significant for patients in each trial. In the first trial, patients relapsed at all levels of detected MRD, whereas in the later trial, in which treatment was more intensive and results were better, the extent of MRD was closely related to the probability of relapse (5 of 5 patients with > 10(-3) MRD, 4 of 10 with 10(-3) to 2 x 10(-5), 0 of 3 with levels below 2 x 10(-5), and 2 of 26 with no MRD detected). Early quantification of leukaemic cells after chemotherapy may be a successful strategy for predicting outcome and hence individualizing treatment in childhood ALL, because the results indicate both in-vivo drug sensitivity of the leukaemia and the number of leukaemic cells that remain to be killed by post-induction therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

GATA-1 is expressed in acute erythroblastic leukaemia.

Previous studies have demonstrated the expression of GATA-1 (a DNA-binding nuclear protein) in erythrocytes, megakaryocytes, eosinophils, basophils, mast cells, early marrow progenitor cells and in mouse and human erythroid leukaemia cell lines. We studied 31 bone marrow specimens from patients with acute myeloid leukaemia (AML) for GATA-1 expression by reverse transcriptase/polymerase chain reaction (RT/PCR) analysis. GATA-1 expression was detected in all of the patients with erythroleukaemia, and in one of nine patients with megakaryoblastic leukaemia, but absent from 17 patients with French-American-British (FAB) M1-5 leukaemia. In AML, GATA-1 expression is indicative of differentiation to the erythroid and possibly megakaryocytic lineages, analogous to its expression in normal haemopoiesis.

Bone Marrow↗
PubMed1994

Intellectual, educational, and behavioural sequelae after cranial irradiation and chemotherapy.

Cognitive and educational sequelae are inconsistently reported in children treated with cranial irradiation for acute lymphoblastic leukaemia. This study investigated differences in these skills after cranial irradiation, controlling the effects of chemotherapy and psychosocial factors. Three groups were evaluated: 100 children diagnosed with acute lymphoblastic leukaemia and treated with cranial irradiation and chemotherapy; 50 children diagnosed with acute lymphoblastic leukaemia or other cancers and treated with chemotherapy alone; and a healthy control group of 100 children. Children in the clinical groups stopped treatment at least two years before evaluation and had no history of relapse. Children were aged between 7 and 16 at the time of assessment. Evaluation included cognitive, educational, and behavioural measures. Analyses found that children receiving cranial irradiation and chemotherapy performed more poorly than non-irradiated groups on intellectual and educational tests, with verbal and attentional deficits most pronounced. Children receiving chemotherapy alone performed similarly to controls, suggesting such treatment is not associated with adverse neurobehavioural sequelae.

Adolescent↗