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S J Proctor

Publications and source records attributed to S J Proctor.

At least 19 recordsLinked to original sources
PubMed2001

The levels of TNF alpha, IL4 and IL10 production by T-cells in B-cell chronic lymphocytic leukaemia (B-CLL).

Tumour necrosis factor alpha (TNF alpha), interleukin (IL) 4 and IL10 are important for the growth and survival of the leukaemic cells in B-cell chronic lymphocytic leukaemia (B-CLL). The present study investigates the production of TNF alpha, IL4 and IL10 in patients with B-CLL. Significant increases in the TNF alpha and IL4 mean levels compared to normal control CD2(+)-cells were observed for B-CLL lymphocytes (TNF alpha: P=0.0004 and IL4: P=0.0026). By contrast, the mean level of IL10 produced by purified B-CLL CD2(+)-cells was significantly lower than that seen with normal control T-cells (P=0.0136). No significant difference in the percentage (%) of T-cells that expressed cytoplasmic TNF alpha, IL4 and IL10 was observed between B-CLL and normal T-cells. However, a significant increase in the mean level of intracellular TNF alpha and IL4 expression was observed in B-CLL compared with normal control T-cells (TNF alpha: P=0.031; IL4: P=0.0027). The increased expression of cytoplasmic TNF alpha and IL4 appeared to be associated with increased cytokine production in the tested samples. The differences observed with some B-CLL cases in the production of TNF alpha, IL4 and IL10 by peripheral blood T-cells may suggest survival mechanisms for the leukaemic cells in these patients.

CD4-CD8 Ratio↗
PubMed2001

Validation of the Hasford score in a demographic study in chronic granulocytic leukaemia.

Chronic granulocytic leukaemia (CGL) is a rare disease. For most patients the only curative treatment (an allogeneic stem cell transplant) is not available. Survival varies between a few months to many years from diagnosis, and an accurate prediction of the duration of survival could help patients and clinicians make informed decisions about the many treatment options. In 1984, the Sokal score was introduced to stratify patients into risk groups. Recently, a new prognostic scoring system was proposed by Hasford and co-workers for interferon treated patients. We have analysed survival on an unselected population based cohort of patients using both the Hasford and the Sokal scores. In the group overall, neither score was predictive of survival, but in younger patients (< 60 years) treated with interferon, the Hasford score was highly predictive of survival, dividing patients into groups with a five year survival of 77% (45 patients) v 33% (six patients) v 14% (31 patients) (p = 0.01).

Adolescent↗
PubMed2001

Gamma-linolenic acid induces apoptosis in B-chronic lymphocytic leukaemia cells in vitro.

Gamma linolenic acid (GLA) is cytotoxic to many types of human cancer cells. Most chemotherapeutic agents are cytotoxic by inducing apoptosis. We examined the apoptotic activity of GLA on purified B-cells isolated from patients with B-cell chronic lymphocytic leukaemia (B-CLL) and from normal individuals. GLA significantly increased the degree of apoptosis in B-CLL B-cells after 24 hours of culture. The mean percentage of cells undergoing apoptosis when cultured in medium alone (spontaneous apoptosis) was 20% (range: 7 to 31%) (n=25) and in the presence of GLA (5 microg-60 microg) was: 42%-95%. In the presence of GLA 5 microg/ml and dexamethasone the degree of apoptosis was 86% (range: 72 to 100%). GLA induced apoptosis in B-CLL B-cells at a higher level than that observed with normal B-cells at all lower concentrations tested 5, 10 and 15 microg/ml: P=0.045; 0.027 and 0.022, respectively. At 30 microg/ml of GLA, no significant difference in the percentage of cells displaying apoptosis between B-CLL and normal B-cells was observed (P=0.075). GLA induced apoptosis in B-CLL T-cells at both 10 and 30 microg/ml. The degree of apoptosis in normal T-cells with GLA was also significant at the higher concentration of 30 microg/ml. Interleukin 4 (IL4), a viability factor in B-CLL, and vitamin E, an anti-oxidant, protected B-CLL B-cells against GLA (20 microg/ml)-induced apoptosis. These results demonstrate that GLA induces apoptosis in B-CLL B- and T-cells cells in vitro and that they are more susceptible to GLA-induced apoptosis than normal peripheral blood B- and T-cells.

Antibodies, Monoclonal↗
PubMed2000

T-cell frequency analysis does not predict the incidence of graft-versus-host disease in HLA-matched sibling bone marrow transplantation.

BACKGROUND: Graft-versus-host disease (GVHD) is a major and sometimes fatal complication of allogeneic bone marrow transplantation (BMT). The prediction of GVHD remains an important issue in preventing morbidity and mortality after allogeneic BMT. In the past 10 years, there has been great interest in using the frequency analysis of alloreactive helper and cytotoxic T lymphocyte precursors (HTLp and CTLp) to detect recipient-specific alloreactivity and thus predict GVHD in HLA-matched related and unrelated BMT. However, the results remain controversial. The intention of the present study was to investigate whether alloreactive HTLp and CTLp frequencies measured in donor peripheral blood before BMT would be a useful predictor for the occurrence of acute GVHD after HLA-matched sibling BMT. METHOD: A combined limiting dilution assay was used to determine alloreactive HTLp and CTLp frequencies for 42 HLA-matched sibling patient/donor pairs. The pretransplantation host-reactive HTLp and CTLp frequencies were then correlated with post-transplantation clinical outcomes of acute GVHD. The association between HTLp/CTLp frequencies and the incidence of acute GVHD was determined using the Fisher's exact test. RESULTS: The mean values of HTLp and CTLp frequencies for this cohort of HLA-matched sibling patient/donor pairs were 1:321,322 (range 1:71,000 to 1:1000,000) and 1:195,260 (range 1:3,717 to 1:1000,000), respectively. Acute GVHD (> or =II) was observed in one of four patients with high (>1:100,000) HTLp frequencies and 20 of 36 patients with low (<1:100,000) HTLp frequencies. Similarly, 6 of 10 patients with high (>1: 100,000) CTLp frequencies and 14 of 29 patients with low (<1:100,000) CTLp frequencies developed acute GVHD (> or =II). The overall correlation between hostreactive HTLp/CTLp frequencies and the incidence of acute GVHD in this cohort of patients was 42.5% and 53.9%, respectively. There was no significant difference in the incidence of acute GVHD between the patients with either high or low host-reactive HTLp/ CTLp frequencies (P=0.331 and 0.716, respectively). The data were also analyzed separately for the adult patient group based on GVHD prophylaxis with either cyclosporine alone or the combination of cyclosporine and methotrexate. Within these two prophylaxis groups, neither HTLp nor CTLp frequencies correlated with acute GVHD. CONCLUSION: Host-reactive HTLp and CTLp frequency analysis did not provide informative prediction for the occurrence of acute GVHD after HLA-matched sibling BMT.

Acute Disease↗
PubMed2000

Population-based study of the pattern of molecular markers of minimal residual disease in childhood and adult acute lymphoblastic leukemia: an assessment of the practical difficulty of representative sampling for trial purposes. Northern Region Haematology Group.

BACKGROUND: The prevalence, in unselected patients with acute lymphoblastic leukaemia (ALL), of clonal rearrangements suitable for minimal residual disease (MRD) studies has not been formally investigated. PROCEDURE: This was a prospective, demographic study of the frequency of molecular markers of MRD in all patients with ALL presenting over 5 years within the Northern Health Region of England (population 3.1 million). Presentation marrow samples were examined to detect informative markers. RESULTS: One hundred twenty-four children (age <15 years) developed non-Burkitt ALL. No material was available for study in 21. Eighty-six had clonal gene rearrangements (BCR/ABL, immunoglobulin heavy chain (IGH) and/or T cell receptor (TCR) gene rearrangements). All entered remission; 84 (68% of the original cohort) survived to become eligible for MRD studies. One hundred sixteen adults developed ALL, of whom 48 were not studied due to insufficient cellular material in the bone marrow aspirate or to logistical problems in central referral of samples from other hospitals. Material from elderly adults (age >55 years) was less likely to be sent for analysis, 36% vs. 59% (P = 0.024). Thirty-eight had BCR/ABL and/or IGH/TCR gene rearrangements. Thirty-one (27% of the original cohort) entered remission and became eligible for MRD studies. Informative gene rearrangements were more common in children than adults (83% vs. 63%, P < 0.003). CONCLUSIONS: The results reveal substantial potential, unintentional, selection bias. Large-scale multicentre studies of MRD in children may well produce clinically relevant and representative data. Those who mount similar studies in adults should not assume they will be similarly representative or as successful in accrual of material.

Adolescent↗
PubMed2000

Primary treatment of low-grade non-Hodgkin's lymphoma using an all oral anthracycline-containing regimen, chlorambucil, idarubicin, dexamethasone (CID)--a phase II study.

PURPOSE: The majority of patients with low-grade non-Hodgkin's lymphoma (LGNHL) are in the older age groups and are thus less able to tolerate aggressive treatment. Chlorambucil, alone and in combination, has been widely accepted as the initial treatment of choice for many years. The availability of an anthracycline which could be given orally in combination with chlorambucil and steroid led us to investigate the efficacy and toxicity of this novel regimen. METHODS: Patients (age less than 70 years) with a histologically confirmed diagnosis of LGNHL (Kiel classification) were eligible for the study if they had no previous chemotherapy. Treatment consisted of chlorambucil 20 mg/ m2 daily for 3 days given on each day in three divided doses, idarubicin 10 mg/m2 for 3 days before breakfast, and dexamethasone 4 mg twice daily for 5 days. All drugs were given orally. Treatment was repeated every 21 days for a maximum of six courses. The regimen was assessed for toxicity and response. RESULTS: A total of 72 patients were registered, and 64 were eligible (median age 52 years). Toxicity was assessed for all cycles given (347). The predominant toxicity was haematological, but in only one course did grade 4 neutropenia (less than 0.5 x 10(9)) occur. Alopecia was not a problem. Full doses of the treatment were administered to 40% of the patients, with no delays or dose reductions. The overall response rate was 83%. Six patients had static disease and two progressed on treatment. Lactate dehydrogenase (LDH) was found to be a good predictor of response to treatment. Of 12 patients documented to have raised LDH, 5 failed to respond to treatment, compared to 1 of 32 patients who had a normal LDH (chi2 10.65, P < 0.002). With a minimum follow-up of 4 years for all patients actuarial 5-year event-free survival was 22% and overall survival was 65%. However, in patients with best and intermediate risk LGNHL (by the SNLG Prognostic Index for Low Grade Disease) overall survival are 88% and 64%, respectively. CONCLUSIONS: This novel regimen was effective and well tolerated.

Administration, Oral↗
PubMed2000

Constrictive pericarditis post allogeneic bone marrow transplant for Philadelphia-positive acute lymphoblastic leukaemia.

We describe two cases of severe constrictive pericarditis arising after allogeneic BMT conditioning involving total body irradiation and melphalan to treat Philadelphia-chromosome positive ALL. Both patients required pericardectomy, resulting in marked improvement in ventricular filling. However, a degree of right-sided cardiac failure persisted in both patients secondary to restrictive cardiomyopathy. Constrictive pericarditis has not been previously described after BMT, but has been observed following thoracic radiotherapy for malignancy, usually involving a substantially higher radiation dose. Pericardial constriction and restrictive cardiomyopathy should be considered as causes of breathlessness and/or oedema occurring late after BMT. Bone Marrow Transplantation (2000) 25, 571-573.

Adult↗
PubMed2000

Haematologists' approaches to the management of adolescents and young adults with acute leukaemia.

Approaches to the management of adolescents and young adults with acute leukaemia were investigated by sending a questionnaire to hospitals identified as having diagnosed or treated patients aged 15-29 years. The responses demonstrated the types of hospital treating these patients, the haematologists' perceived practice for entry of patients to Medical Research Council (MRC) leukaemia trials and reasons for non-entry. Data were linked to MRC trials data to determine the proportion of patients aged 15-29 years at diagnosis in responding hospitals actually treated in MRC leukaemia trials in the 5 years preceding the questionnaire. Eighty-two per cent of haematologists stated that they entered patients 'always' or 'whenever possible' for acute myeloid leukaemia (AML) and 76% for acute lymphoblastic leukaemia (ALL), but actual entry rates from the study hospitals were 46% of 239 AML patients and 36% of 182 ALL patients. The reasons most commonly reported for not entering eligible patients to national leukaemia trials were clinician preference for one arm of an MRC trial, a regional study or non-trial protocol, and concern about workload and ethical approval.

Acute Disease↗
PubMed2000

Monoclonal antibodies recognizing CD5, CD10 and CD23 in formalin-fixed, paraffin-embedded tissue: production and assessment of their value in the diagnosis of small B-cell lymphoma.

AIMS: Assessment of the expression of antigens CD5, CD10 and CD23 can be of value in the differential diagnosis of small B-cell lymphoma. Correct subclassification is important since optimal treatment regimes differ between the subtypes. The aim of this study was to generate monoclonal antibodies recognizing these antigens in paraffin-embedded tissue and to assess their efficacy using a panel of cases of small B-cell lymphoma of various subtypes. METHODS AND RESULTS: For each antibody synthetic recombinant protein and conventional murine hybridoma technology was employed. Monoclonal antibodies effective in formalin-fixed, paraffin-embedded tissue were successfully generated, designated NCL-CD5-4C7, NCL-CD10-270 and NCL-CD23-1B12, respectively. A series of 58 cases of small B-cell lymphoma including examples of each subtype (lymphocytic, follicle centre cell, mantle cell, marginal zone and lymphoplasmacytoid) was assembled and immunostaining for the respective antigens carried out using the monoclonal antibodies produced. Our results indicate that the antibodies are specific for their respective antigens and give the predicted phenotypic profile in the small B-cell lymphoma subtypes. CONCLUSIONS: These novel monoclonal antibodies may be of value in routine diagnostic practice.

Animals↗
PubMed2000

High dose ifosfamide in combination with etoposide and epirubicin followed by autologous stem cell transplantation in the treatment of relapsed/refractory Hodgkin's disease: a report on toxicity and efficacy.

Patients with Hodgkin's disease (HD) refractory to first line chemotherapy and those who have rapid or multiple relapses have a very poor prognosis. With the increasing use of hybrid chemotherapy these patients will have been exposed to many of the drugs active in HD so it is important to develop salvage regimens that are novel and demonstrate activity in this group of patients. We report the use of a continuous high dose infusion of ïfosfamide at a dose of 9g/m(2) over 3 days in combination with etoposide and epirubicin followed by autologous stem cell transplant with either BEAM or Melphalan/VP16 conditioning in this difficult group. Forty six patients (28M:18F) with a median age of 28 years (range 13-45) were treated. Overall 39 out of 46 (85%) patients responded to treatment, with 17 achieving complete remission and 11 a good partial remission; 28 proceeded to autologous bone marrow/stem cell transplantation. In total, 23 patients are alive and in continuous remission with a follow up of between 12 and 61 months. Median overall survival for the whole group is 36 months. Haematological toxicity, particularly neutropenia (WHO grade IV), was observed in all cases but improved over the 3 courses of treatment in all patients. Non-haematological toxicity was not a major problem; no significant cardiac, hepatic, renal, pulmonary or neuro toxicity was observed and there were no deaths on treatment. This regime shows promise in patients with difficult Hodgkin's disease and warrants further study.

Adolescent↗
PubMed2000

Tumour necrosis factor gene polymorphisms in lymphoproliferative disease.

Tumour necrosis factor (TNF) alpha is involved in the pathogenesis of established lymphoproliferative disease. Serum levels of TNFalpha and its soluble receptors are above normal values in B-cell chronic lymphocytic leukaemia (B-CLL) and they are valuable prognostic markers in lymphoma patients. The production of TNFalpha is genetically controlled. Altered synthesis of TNFalpha has been associated with polymorphisms at the TNF gene cluster (i.e. TNFA, TNFB and LTB). In the present study, we evaluated the prevalence of the known high TNFalpha- and TNFbeta- producing alleles TNF1, TNF2 of the TNFA gene, TNFB1, TNFB2 alleles of the TNFB gene and of the polymorphic alleles TNFd1, d2, d3, d4 and d5 of the microsatellite TNFd in patients with B-CLL, non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). This study demonstrates that there is no difference in the frequency of the tested TNF alleles between normal controls and cohorts of patients with lymphoproliferative disease. These results indicate that TNF alleles are not genetic predisposing factors in the development of these diseases.

Alleles↗
PubMed1999

A NICE programme.

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Epidemiologic Methods↗