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Biomedical subjects

J Treleaven

Publications and source records attributed to J Treleaven.

At least 127 records · Page 7Linked to original sources
PubMed1993

Feasibility and efficacy of maintenance chemotherapy following autologous bone marrow transplantation for first remission acute lymphoblastic leukaemia.

Thirty-eight patients with poor risk ALL in first remission received maintenance chemotherapy following ABMT. Patients were conditioned for ABMT with high-dose melphalan and single fraction total body irradiation. Maintenance chemotherapy was commenced in a total of 26 patients and was tolerated to a median daily dose of 6-mercaptopurine of 40.5 mg/m2 and a median weekly dose of MTX 8.3 mg/m2. Twenty patients remain alive in first remission with a projected disease-free survival of 50% and a median follow-up in survivors of 200 weeks (range 48-387 weeks). Eleven patients have relapsed at a median of 4.5 months from ABMT. These patients were compared with remission patients with ALL receiving conventional chemotherapy on the United Kingdom Medical Research Council trials UKALL X and XA. After stratifying for major risk factors and allowing for the delay from remission to transplant, we have shown a significant reduction in the risk of relapse after ABMT (p = 0.04). Disease-free survival was not significantly increased due to transplant-related toxicity. This study suggests that maintenance chemotherapy to prevent relapse after ABMT for ALL is well tolerated and warrants assessment in a formal controlled trial.

Adolescent↗
PubMed1992

Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation.

Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.

Adult↗
PubMed1992

Tumour lysis following hydrocortisone prior to a blood product transfusion in T-cell acute lymphoblastic leukaemia.

The acute tumour lysis syndrome is a well recognised complication of chemotherapy for lymphoid malignancies. There are few reports, however, of this complication after corticosteroid therapy alone. We report a case of T-cell acute lymphoblastic leukaemia who developed the biochemical picture of tumour lysis after two doses of hydrocortisone given prior to platelet transfusion. Prophylactic corticosteroids prior to blood product infusion should be reserved for patients who have experienced febrile or allergic reactions in the past and it is suggested that they should only be administered to patients with active lymphoid malignancies with due caution.

Adolescent↗
PubMed1992

Colony-stimulating activity in the serum of patients with hemopoietic malignancies after intensive chemotherapy/radiotherapy: its augmentation by GM-CSF in vivo and interleukin 4 in vitro.

Colony-stimulating activity (CSA) in the serum of patients with hematological malignancies increased substantially after intensive therapy with cyclophosphamide/busulfan, cyclophosphamide/total body irradiation, or melphalan/total body irradiation. This was not dependent on patients receiving allogeneic bone marrow transplantation (ABMT) or autologous bone marrow rescue (ABMR). In 44 of 62 patients CSA was maximum approximately 7 days after chemotherapy/radiotherapy, whereas in 18 of 62 patients CSA was maximum between 9 and 20 days after therapy and decreased thereafter. The time course of CSA was not dependent on disease and was not affected by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) given as a continuous infusion for 14 days after therapy; however, serum from patients receiving rhGM-CSF produced significantly more colonies from donor bone marrow than serum from patients who did not receive the cytokine (p = 0.013). Despite the early peak in CSA in the majority of patients, there was no correlation between the time at which CSA was maximum and the return of patients' neutrophils to 500/microliters. Recombinant human interleukin 4 (IL-4) increased the number of granulocyte-macrophage colony-forming unit colonies, principally granulocyte colony-forming unit colonies, from normal bone marrow exposed to patients' serum after intensive therapy and antibody to GM-CSF reduced colony numbers. The results suggest that after intensive therapy granulocyte colony-stimulating factor (G-CSF) as well as GM-CSF is released into the serum and, in addition to acting directly with G-CSF, IL-4 may stimulate mononuclear cells to produce and/or release G-CSF.

Bone Marrow Cells↗
PubMed1992

No increase in relapse in patients with myeloid leukaemias receiving rhGM-CSF after allogeneic bone marrow transplantation.

Twenty patients with leukaemia received recombinant human GM-CSF (rhGM-CSF) after allogeneic bone marrow transplantation (BMT) in a double blind controlled trial, with a significant promotion of granulopoiesis when compared with 20 control patients. The follow-up in survivors is now sufficiently long to assess the potential for promotion of relapse in the patients with myeloid leukaemias. Six patients with myeloid leukaemias are alive 22-38 months after transplantation. Eight other patients with myeloid leukaemias died within 12 weeks of transplantation without active active disease. None of these 14 patients with myeloid leukaemias have relapsed. This study supports the view that rhGM-CSF does not increase the probability of relapse after allogeneic BMT in patients with myeloid leukaemia.

Bone Marrow Transplantation↗
PubMed1991

A prospective comparison between magnetic resonance imaging, meta-iodobenzylguanidine scintigraphy and marrow histology/cytology in neuroblastoma.

A prospective comparison between magnetic resonance imaging (MRI), 123I meta-iodobenzylguanidine (mIBG) scintigraphy and posterior iliac crest marrow aspiration and trephine biopsy in 30 assessments (19 patients) showed concordance between the three techniques in 16 assessments (53.3%). In 10 (33.3%), MRI and mIBG revealed abnormalities not detected by marrow biopsy. MRI was the only technique to demonstrate marrow abnormality in four assessments (13.3%). In addition, MRI revealed more sites of abnormality in 16 parallel assessments. We conclude that MRI shows promise as a non-invasive means of detecting bone marrow infiltration by neuroblastoma, but that further evaluation of the specificity of MRI in this setting is indicated.

3-Iodobenzylguanidine↗
PubMed1991

Human recombinant GM-CSF in allogeneic bone marrow transplantation for leukaemia: double-blind placebo controlled trial.

A double-blind randomised trial compared 20 patients with leukaemia receiving human recombinant granulocyte macrophage colony stimulating factor (GM CSF), with 20 patients receiving placebo for 14 days after allogeneic matched sibling bone marrow transplantation. The median neutrophil count at 14 days was significantly higher in the GM CSF group (1.90 vs. 0.46 x 10(9)/l). The duration of hospital stay, the number of antibiotic days, and the number of fever days was the same for both patient groups. The lymphocyte count was significantly higher in the GM-CSF group than in the placebo group between days 10 and 15 after transplantation. The GM-CSF group had lower haemoglobin concentrations and platelets counts, and higher plasma urea creatinine and bilirubin, than the placebo group. There was no evidence that GM CSF was associated with a greater incidence of leukaemic relapse.

Bone Marrow Transplantation↗
PubMed1990

Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia: double-blind, placebo-controlled trial.

In a randomised, double-blind trial 20 patients with leukaemia received human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and 20 received placebo, for 14 days after allogeneic, matched sibling, bone-marrow transplantation. The neutrophil count recovered to 0.5 x 10(9)/l 3 days earlier in the GM-CSF group than in the placebo group (not significant), and the median neutrophil count at 14 days was significantly higher in the GM-CSF group (1.90 vs 0.46 x 10(9)/l). The lymphocyte count was significantly higher in the GM-CSF than in the placebo group between days 10 and 15 after transplantation, but this difference was not associated with a higher incidence of graft-versus-host disease. There was no evidence that GM-CSF was associated with a greater incidence of leukaemic relapse. The GM-CSF group had lower haemoglobin concentrations and platelet counts and higher plasma urea, creatinine, and bilirubin than the placebo group. The duration of hospital stay was the same for both patient groups. Further studies are now indicated to assess the overall effect of GM-CSF on outcome after allogeneic bone-marrow transplantation.

Adolescent↗
PubMed1990

Bone-marrow transplant from father to son and subsequent graft from son to father.

An 11-year-old boy with acute myeloblastic leukaemia in first remission received an allogeneic mismatched bone-marrow transplant (BMT) from his father in 1979; subsequent HLA typing showed that his haemopoietic system had been repopulated by the donor cells. In 1986 hypereosinophilic syndrome, secondary to a T-cell lymphocytic lymphoma, developed in the father, then aged 45 years. A full haematological remission was obtained by means of standard acute lymphoblastic leukaemia treatment. He then received melphalan, total body irradiation, and a BMT from his son. Graft-versus-host disease was transient in both patients, and father and son remain well and disease-free 20 months and 10 years, respectively, after BMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Prevention of breast cancer with tamoxifen--an update on the Royal Marsden Hospital pilot programme.

An 'anti-oestrogen' such as tamoxifen may protect prophylactically against breast cancer. At the Royal Marsden Hospital, the blind randomised feasibility study of tamoxifen 20 mg per day versus placebo in 200 healthy women has been extended into a pilot trial. A total of 435 women with a family history of breast cancer have been accrued. Compliance, acute toxicity, clotting factors, lipids and bone mass were assessed. The pilot trial has confirmed the findings of the feasibility study. Compliance was high and the frequency of side-effects was similar in both groups, except for a significant increase in hot flushes in the tamoxifen-treated women (33 vs. 17%). Bone mass and clotting factors were not affected. Tamoxifen significantly reduced serum cholesterol, low-density lipoprotein cholesterol (LDLC) and apolipoprotein B levels in post-menopausal women. In premenopausal women, the effects on lipids and lipoproteins was smaller with a significant fall in total serum cholesterol and LDLC only. The trial has approval to accrue up to 1000 women.

Breast Neoplasms↗
PubMed1990

High-dose cytosine arabinoside plus etoposide as initial treatment for acute myeloid leukaemia: a single centre study.

In a single centre, 52 newly diagnosed patients with acute myeloid leukemia (AML) under the age of 56 years received induction chemotherapy commencing with high-dose cytosine arabinoside (Ara-C) and etoposide (Protocol BF11), followed by Ara-C, 6 thioguanine (6TG). A total of 67% of patients entered remission using these drugs. An anthracycline was added for those patients not in remission. The overall remission rate (CR) was 86.5% (45/52), with a minimum follow-up of 90 days. Patients are hospitalised for relatively short periods, and consequently require less blood product and antibiotic support. Patients in continuing first remission following induction with Ara-C and etoposide are similar in number to those in continuing first remission who initially received an anthracycline. This would imply that the efficiency of Ara-C and etoposide in inducing long-term disease-term survival is comparable with anthracycline-containing regimens. We conclude that high-dose Ara-C and etoposide used in the first induction cycle for treating AML have good antileukaemic effect with acceptable toxicity.

Adolescent↗
PubMed1990

Evidence that multiple myeloma may be regulated by homeostatic control mechanisms: correlation of changes in the number of clonogenic myeloma cells in vitro with clinical response.

Myeloma colonies (MY-CFUc) could be grown in vitro for 6 months (median time) after a group of 12 myeloma patients had reached complete remission (CR). In a second group of 25 patients MY-CFUc increased in 17/25 and GM-CFUc in 20/25 patients after cyclophosphamide even though 24/25 patients had a partial response to VAMP and one was in CR. These data suggest that cell killing by cyclophosphamide stimulates residual tumour cells into proliferation and adds further support to the idea that myeloma is under some degree of homeostatic control which may be analogous to that in normal bone marrow. Although lymphoplasmacytoid myeloma cells may be more drug resistant than plasmacytoid myeloma cells in vitro, it was not possible to conclude that the emergence of lymphoplasmacytoid cells at relapse was indicative of resistance to further treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Thrombocytopenia after bone marrow transplantation for leukaemia: changes in megakaryocyte growth and growth-promoting activity.

Megakaryocyte growth-promoting activity (MK-GPA) was scored on a scale of 0-3 in the serum of 23 patients up to 120 d following bone marrow transplantation (BMT) for leukaemia. Nine of 19 allografts and two of four autografts had thrombocytopenia requiring platelet transfusion more than 30 d after BMT. There was a close correlation between MK-GPA and platelet count. MK-GPA reached a maximum before day 30 after BMT but remained elevated in patients with persisting thrombocytopenia secondary to poor engraftment, graft-versus-host disease (GVHD) or relapse. Recent platelet transfusion did not suppress serum MK-GPA. Two of four patients undergoing autologous BMT for acute myeloid leukaemia (AML) showed delayed platelet recovery and persistence of MK-GPA in the serum. Seven further AML remission marrows were tested for megakaryocyte production before or after autologous BMT, using pooled sera with known MK-GPA activity. Megakaryocyte generation was reduced before BMT and absent in post transplant samples. This failure of MK production was not corrected by T-cell depletion or by the presence of adherent cells from normal marrow. We conclude that thrombocytopenia after BMT is associated with an appropriate increase in MK-GPA levels in response to a reduction in the megakaryocyte pool rather than the platelet pool, and that persisting thrombocytopenia after autologous BMT is due to decreased numbers of available megakaryocyte precursors.

Adolescent↗