Showing papers by "Clinical Trial Service Unit published in 1991"

How to avoid bias when comparing bone marrow transplantation with chemotherapy.

Abstract: It is important to know whether the survival of patients receiving an allogeneic bone marrow transplant (BMT) is better than that of patients receiving "conventional" treatment and, if BMT is better, to know how much better. Unfortunately, this information is surprisingly difficult to obtain accurately. Most studies that have attempted to define the value of BMT have been subject to varying degrees of bias because of the problems of identifying a "conventional chemotherapy" control group with which the outcome of patients who have received BMTs can be compared. A common bias arises when disease-free survival of BMT patients is compared with that of all other remitters. Early failures are then automatically assigned to the chemotherapy group even if they have donors and so would have gone on to a BMT had they not relapsed or died. Since some patients receive BMTs many months (or even years) after achieving remission-when their prognosis is already much improved-the definition of "early failure" is problematic. Nevertheless, although it is very rarely used, an adequate statistical method does exist to overcome this problem. Careful analysis cannot, however, overcome the problem of selection bias: patients selected for BMT are likely to have better (or worse) prognosis than patients who are treated conventionally. The only really satisfactory way of assessing the value of BMT is to conduct randomised trials comparing BMT with no BMT - or with extra chemotherapy. Several such studies are currently being undertaken assessing the role of autologous BMT in AML.(ABSTRACT TRUNCATED AT 250 WORDS)

British Heart Foundation surveys (1987 and 1989) of United Kingdom treatment policies for acute myocardial infarction.

Abstract: Consultant physicians and cardiologists were surveyed early in 1987 and 1989 to document the management policies for the treatment of acute myocardial infarction in United Kingdom hospitals and to assess the influence of major clinical trials on these policies. The response rate to both these surveys was high (84% (1178 physicians) in 1987 and 76% (982 physicians) in 1989). The percentage of physicians that reported using antiplatelet therapy "routinely" in acute myocardial infarction rose from 9% in 1987 to 84% in 1989 while those who reported using it "rarely or never" fell from 42% to 3%. Similarly, "routine" use of fibrinolytic therapy rose from 2% to 68%, and use "rarely or never" fell from 53% to 3%. This increase in the reported use of fibrinolytic therapy was accompanied by greater certainty about its efficacy and relative safety and by a general widening of the indications for its use. The use of other treatments in acute myocardial infarction (for example, the general use of anticoagulants, beta blockers, nitrates, calcium antagonists, or prophylactic antiarrhythmic agents) seemed to change little during this period, although the routine use of coronary angiography and oral anticoagulants after fibrinolytic therapy fell substantially between 1987 and 1989 (from 23% to 4%, and from 24% to 7% respectively). Fibrinolytic and antiplatelet therapy were accepted into the routine management of myocardial infarction during a relatively short period that coincided with the reporting of several positive controlled trial results. Clinical trials have rarely been seen to have had such a great impact on practice. In this case the rapid acceptance of the trial results may have been due to the consistency and reliability of the estimates of the size of the benefits (and risks) of therapy seen in these unusually large studies.

Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non‐cirrhotic portal hypertension. RESULTS FROM MRC CML II TRIAL COMPARING BUSULPHAN WITH BUSULPHAN AND THIOGUANINE

Abstract: Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML.

Prognostic importance of Sudan Black positivity: a study of bone marrow slides from 1,386 patients with de novo acute myeloid leukaemia.

Abstract: Analysis of bone marrow slides from 1,386 patients entered into the Medical Research Council's 8th and 9th trials in Acute Myeloid Leukaemia confirmed that features associated with differentiation in blast cells, in particular increasing Sudan Black (SB) positivity, were the most important morphological features for predicting remission achievement (P = 0.002) and hence survival (P less than 0.0001). SB positivity was also weakly predictive of remission duration (P = 0.05). A low complement of maturing granulocytes was associated with early induction death and a high percentage of blasts with shorter remissions. The few patients with acute promyelocytic leukaemia (FAB M3) had a high haemorrhagic death rate during induction and a low relapse rate. Apart from this, lineage involvement was not predictive of outcome. Multiple lineage leukaemias, in particular those with megakaryocytic and/or erythroid involvement, which had been reported previously to have a poor prognosis, did not have any worse remission rates in this series. When more than one cell line was involved, no combination with particularly good or poor prognosis could be identified. Multivariate analysis suggested that percentage SB positivity was adequate on its own to divide granulocytic leukaemias into poorly differentiated (less than 50% SB +ve) and well-differentiated groups (50% or more SB +ve) without the need for further measurements. This simple and reproducible test was strongly predictive of resistant disease but not of induction deaths. It was of considerably greater prognostic value--and was less open to inter-observer disagreement--than the FAB criteria which are usually used to classify granulocytic lineage leukaemias into the M1 and M2 subgroups. It is proposed that greater than or equal to 50% of blasts with SB positivity should replace blasts greater than 10% of maturing myeloid cells for this sub-categorization between M1 and M2.