High-dose therapy: the Third UCH Meeting.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Biomedical subjects
R Chopra
Publications and source records attributed to R Chopra.
Liposomal amphotericin B in the treatment of fungal infections in neutropenic patients: a single-centre experience of 133 episodes in 116 patients.
Liposomal amphotericin B (AmBisome) was used for suspected or confirmed fungal infection complicating 133 neutropenic episodes in 116 patients not tolerating, or not responding to, conventional amphotericin. Adverse effects were infrequent and no significant renal impairment resulted. Acute reactions occurred in five patients, reversible hepatic dysfunction in 23, and hypernatraemia in 17. The putative mycosis resolved with AmBisome treatment in 81 episodes (61%) and progressed with fatal outcome in 25 (19%), but the diagnosis was equivocal in most, and in 27 episodes (20%) evidence indicating nonfungal pathogenesis emerged. Treatment efficacy is, however, evaluable in those with proven aspergillosis. 13/17 patients with confirmed invasive aspergillosis responded to AmBisome (77%), conventional amphotericin having failed in 11. Treatment was successfully discontinued when the neutrophil count was < 1 x 10(9)/l in eight responders (61%). In four further patients treated for suspected aspergillosis, disseminated infection was documented at post-mortem, but the true incidence is unknown. This analysis confirms that AmBisome is well tolerated and effective against invasive mycoses in neutropenic patients, and may salvage patients when conventional amphotericin proves excessively toxic or ineffective.
Adolescent↗
Detection and significance of bone marrow infiltration at the time of autologous bone marrow transplantation in Hodgkin's disease.
Bilateral iliac crest biopsies were performed at the time of bone marrow (BM) harvest in patients with poor-risk Hodgkin's disease (HD) undergoing autologous bone marrow transplantation (ABMT). 67 consecutive patients with normal trephine biopsies (58 unilateral; nine bilateral) taken 2 weeks prior to harvest were studied. Nine (13%) of patients had BM infiltration with HD on the harvest biopsies. These patients had all previously had only unilateral biopsies. Three patients did not proceed to ABMT because disease progression became clinically apparent, but the remaining six patients were infused with involved marrow. One patient died 6 weeks post ABMT, with no evidence of disease at post-mortem. One patient showed no response to ABMT and four patients either had a partial or complete response to ABMT. Of the responders, three patients are now in complete remission at 53, 39 and 33 months past ABMT.
Adolescent↗
The third UCH High Dose Meeting.
The use of high-dose chemotherapy continues to increase in the treatment of a variety of haematological and non-haematological malignancies. At the same time, a greater understanding of haemopoiesis and its regulation has enabled the rapid clinical introduction of a variety of haemopoietic growth factors and peripheral blood stem cell support. Advances in immunology have led to a better understanding of the underlying mechanisms of graft-versus-host disease and the immunology associated with alloBMT. The aim of the UCH High Dose Meeting has been to critically review these advances in light of ongoing and future clinical trials. This report highlights some of the topics discussed.
Academic Medical Centers↗
Intraductal papilloma of the male breast--case report.
Explore the source record for details and available documents.
Breast Neoplasms, Male↗
Factor VIIa and other haemostatic variables following bone marrow transplantation.
Hepatic venocclusive disease causes considerable morbidity and mortality following bone marrow transplantation. There are two hypotheses regarding the aetiology of this syndrome; firstly that changes in plasma coagulation factors and natural anticoagulants lead to a prothrombotic state and secondly that endothelial cell activation stimulates intravascular deposition of fibrin. We have investigated these mechanisms by measuring the changes in proteins C and S and factors VII and X in the post transplant period and by using the plasma concentration of factor VIIa as an in vivo marker of potential endothelial cell tissue factor expression. Protein C fell in both allograft and autograft patients but more so in the allografts. Similar results were found for factors VII and X. These changes were predominantly due to hepatic dysfunction induced by the chemo-radiotherapy. Factor VIIa levels were unchanged in both the allograft and autograft patients. We conclude that there is no convincing evidence for a procoagulant state following BMT as there are both anticoagulant and procoagulant changes. The absence of any changes in factor VIIa levels suggests that tissue factor was not exposed to the general circulation following BMT but does not exclude focal expression at the sites of thrombosis.
Bone Marrow Transplantation↗
Detection and significance of pulmonary Hodgkin's disease at autologous bone marrow transplantation.
Pulmonary Hodgkin's disease (HD) is considered to carry a poor prognosis both at presentation and at relapse. We have therefore studied the incidence and significance of pulmonary involvement in 190 poor risk HD patients undergoing BEAM therapy and ABMT for relapsed or resistant disease. Forty-one of 190 patients (22%) had clinically diagnosed pulmonary HD at some stage of their disease prior to ABMT. In 29 patients, in whom a full set of CT scans was available, the patterns of pulmonary HD were characterised. Four of 29 patients had pulmonary disease at presentation only, 8 of 29 at presentation and ABMT and 17 of 29 developed pulmonary involvement at relapse and proceeded to ABMT with persistent pulmonary disease. The commonest pulmonary abnormalities at presentation and relapse were discrete nodules (72%), masses extending from hilar or mediastinal nodes (34%) and pleural effusion/thickening (28%); 52% had two or more patterns of involvement and 66% had coexistent mediastinal lymphadenopathy. There was no relationship between pattern or bulk of pulmonary involvement and outcome. Consideration of the outcome following ABMT in all 190 patients revealed no significant difference in progression-free survival at 5 years between the pulmonary HD group (43%) and those without lung involvement (48%). Furthermore, there was no significant difference in complete remission or transplant-related death rates between the two groups. This would suggest that pulmonary involvement is not in itself a contraindication to ABMT and some patients with bulky pulmonary disease are capable of long-term survival.
Adult↗
Recent advances in Hodgkin's disease.
Despite the undoubted advances in the therapy of Hodgkin's disease in the past 30 years, there remain a large number of controversial and unresolved issues surrounding the pathogenesis and the treatment of this condition. The aim of this article is to review the current literature in the context of these controversies and to highlight studies that have used modern technologies to give an insight into the pathogenesis of Hodgkin's disease.
Hodgkin Disease↗
Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial.
High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation (ABMT) are increasingly used for the treatment of relapsed and resistant Hodgkin's disease, although there has been no randomised trial of this treatment. The British National Lymphoma Investigation therefore undertook a randomised comparison of high-dose chemotherapy (BEAM = carmustine, etoposide, cytarabine, and melphalan) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue (mini-BEAM) in patients with active Hodgkin's disease, for whom conventional therapy had failed. 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM. All have been followed up for at least 12 months (median 34 months). 5 BEAM recipients have died (2 from causes related to ABMT and 3 from disease progression) compared with 9 mini-BEAM recipients (all disease progression). This difference was not significant (p = 0.318). However, both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT (p = 0.025 and p = 0.005, respectively). Recruitment to the trial became increasingly difficult because patients refused randomisation and requested ABMT. It was therefore closed early (40 patients rather than 66 intended). Nevertheless, we found a dose-response effect in these patients with relapsed and resistant Hodgkin's disease. High doses facilitated by ABMT can lead to better disease-free survival.
Adolescent↗
The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight-year study of 155 patients.
Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarial overall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses > 10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.
Adolescent↗
The effect of bezafibrate treatment on serum alkaline phosphatase isoenzyme activities.
A reduction in serum total alkaline phosphatase (ALP) activity is a well-documented side effect of treatment with bezafibrate and other fibric acid derivatives. To evaluate the effect of bezafibrate treatment on individual ALP isoenzyme activities, 10 patients were studied on two separate occasions, first, after a 6-week period on no drug treatment, and second, after 6 weeks of bezafibrate therapy. On each occasion, serum total ALP and ALP isoenzyme activities and serum gamma-glutamyltransferase (GGT) activity were measured both after fasting and following the ingestion of a standardized high-fat meal rich in long-chain fatty acid triglycerides, as intestinal ALP activity is known to be influenced by dietary fat intake. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured on fasting samples. In the fasting state, bezafibrate treatment resulted in a 25% reduction (P < .01) in serum total ALP activity; liver ALP activity was reduced by 40% (P < .01), and biliary ALP activity was reduced in those patients in whom it was initially detectable, while bone and intestinal ALP activities were unchanged. There was also a 15% reduction (P < .05) in serum GGT activity, but no change in plasma AST or ALT activities. Serum intestinal ALP activity increased significantly (P < .01) by 1 hour following ingestion of the high-fat meal, but treatment with bezafibrate did not change the magnitude of this response. There was no change in the activity of any other ALP isoenzyme following fat ingestion. This study demonstrates that the effect of bezafibrate on serum ALP activity is confined to the liver and biliary isoenzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Acute hepatitis C infection in patients undergoing therapy for haematological malignancies: a clinical and virological study.
Patients receiving multiple transfusions are at risk of acquiring hepatitis C (HCV) infection from a donor population which is unscreened for hepatitis C antibodies (anti-HCV). Prior to the introduction of blood donor screening for anti-HCV in the U.K., a group of patients undergoing therapy for haematological malignancies, with repeatedly abnormal liver function tests, were investigated for acute HCV infection. Thirty-two patients had repeatedly raised serum transaminases, and eight of these (25%) had evidence of an acute HCV infection. The diagnosis was made by the detection of HCV-RNA in the patients' serum using a complementary DNA/polymerase chain reaction (cDNA/PCR) procedure. All eight patients had received myeloablative chemotherapy and three had undergone bone marrow transplantation. HCV infection contributed significantly to the morbidity of this group of patients in the short term whilst they were undergoing treatment for their underlying haematological condition. The long-term effects have yet to be evaluated. In an attempt to decrease hepatic damage due to HCV, three patients were placed on interferon therapy. None showed a sustained reduction in serum transaminases or HCV viraemia. It is hoped that the introduction of anti-HCV screening of blood donors, will reduce the frequency of transfusion-acquired HCV infections. Early observations suggest that this is the case, as we have seen no new cases of HCV infection in our unit since the introduction of donor screening in September 1991.
Acute Disease↗
Randomised vehicle-controlled dose-finding study of glycosylated recombinant human granulocyte colony-stimulating factor after bone marrow transplantation.
A multicentre, randomised vehicle-controlled single-blind dose ranging trial of intravenous recombinant granulocyte colony-stimulating factor (rhuG-CSF) administration after BMT has been performed in 121 patients with non-myeloid malignancies. All the doses of rhuG-CSF used (2-20 micrograms/kg/day) resulted in significant acceleration of neutrophil recovery, and a dose-response effect was apparent (p < 0.05). At the 20 micrograms/kg/day dose of rhuG-CSF the median time taken to achieve a neutrophil count of > 0.5 x 10(9)/1 was reduced from 19 to 13 days (p < 0.001) and the time to achieve a neutrophil count > 1.0 x 10(9)/1 on the first of 3 consecutive days, from 26 to 14 days (p < 0.001). There was a trend to less antibiotic use in the rhuG-CSF recipients and the median time in hospital was markedly reduced by 11-15 days (p < 0.01). There was no toxicity in this study attributable to rhuG-CSF.
Adolescent↗
Effect of aerosolised verapamil and nifedipine in bronchial asthma.
Twenty patients of bronchial asthma were given 5 mg of either nifedipine or verapamil as aerosol therapy in a randomized fashion. Both drugs showed a statistically significant improvement in FVC, PEFR at zero hours lasting through 90-120 minutes. Changes in respiratory rate, pulse rate, blood pressure were insignificant with verapamil while appreciable tachycardia and transient fall in BP occurred with nifedipine therapy.
Administration, Inhalation↗
Hepatic involvement in tuberculosis.
Seventy one cases of pulmonary and extrapulmonary tuberculosis (confirmed by clinical, sputum examination, Skiagram, lymph node or other organ biopsy) and 13 cases of PUO suspected to be tubercular in origin were included in the study. Besides, thorough clinical workup, LFTs and liver biopsy were also done in all cases. LFT alterations were seen in only 5 (7%) cases of tuberculosis while in PUO group, 3 (23%) cases showed deranged LFT. In all, alteration in SGOT/SGPT was most frequent observation. In Liver biopsy, histopathological changes were seen in 63 percent (45 out of 71) of cases of tuberculosis and in 46.16 percent cases of PUO. In tubercular cases, various abnormalities observed were caseating granulomas: 18.30 percent, nonspecific inflammatory infiltration: 25.32 percent, focal Kupffer cell hyperplasia: 11.2 percent and fatty changes: 8.45 percent. Four of the PUO cases, showing Kupffer cell hyperplasia and non-specific inflammatory infiltration responded to antituberculous therapy. Thus it is surmised that though the caseating granuloma is the hallmark of tuberculosis, but nonspecific inflammatory hepatitis and retothelial tubercle nodules may be the forerunner in the evolution of granuloma.
Adolescent↗
Treatment of Hodgkin's lymphoma.
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
Modern trends in bone marrow transplantation for acute myeloid and acute lymphoblastic leukemia.
A greater understanding of the underlying mechanisms of hematopoiesis and leukemogenesis in the clinical management of acute myeloid and lymphoblastic leukemia has led to an improvement in survival from what were invariably fatal diseases. Bone marrow transplantation is increasingly becoming an accepted form of therapy for acute myeloid leukemia and acute lymphoblastic leukemia in certain situations. This review seeks to address some of the recent advances and controversies including whether bone marrow transplantation is more efficacious than modern intensive chemotherapy, the role of autologous bone marrow transplantation and matched-unrelated donor transplants, the graft-versus-leukemia effect, and the role of purging in autologous bone marrow transplantation. Furthermore, advances in supportive therapy including the introduction of hematopoietic growth factors is critically evaluated. Finally, the appropriate timing and role of bone marrow transplantation is discussed in the context of previous ongoing and future clinical trials.
Acute Disease↗
Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: a British National Lymphoma Investigation double-blind, placebo-controlled trial.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is active in enhancing the production of mature myeloid cells in vitro and several phase I/II clinical trials have suggested that its administration may accelerate neutrophil recovery after autologous bone marrow transplantation (ABMT). We have conducted a multicentre randomized double-blind placebo controlled trial in patients with poor prognosis malignant lymphoma receiving an identical high-dose combination chemotherapy regimen with ABMT. 61 patients were entered and 29 in each arm of the trial were evaluated. Treatment with GM-CSF did not affect the period of severe neutropenia (absolute neutrophil count (ANC) of < 0.1 x 10(9)/l) but accelerated recovery to an ANC of 0.5 x 10(9)/l (median 14 d v 20 d in controls, P = 0.001). There was no significant difference in platelet recovery between the groups (GM-CSF group platelet dependent for 25 d v control 19 d, P = NS). The number of positive blood cultures was similar in both groups (GM-CSF 14 v placebo 13) and there were no differences in days of fever > 37.5 degrees C (median 8 v 6) or days on parenteral antibiotics (11 v 10). Patients receiving GM-CSF had a median period of hospitalization following BMT of 24 d (control 25). No significant major toxicity attributable to GM-CSF administration was detected. We have confirmed in a randomized trial that GM-CSF accelerates neutrophil but not platelet recovery following ABMT. We were unable to demonstrate any accompanying changes in clinical outcome and believe that further trials are necessary to assess the clinical value of GM-CSF in BMT.
Adolescent↗