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BACKGROUND: Patients with multiple myeloma treated with lenalidomide maintenance therapy have improved progression-free survival, primarily following autologous stem-cell transplantation. A beneficial effect of lenalidomide maintenance therapy on overall survival in this setting has been inconsistent between individual studies. Minimal data are available on the effect of maintenance lenalidomide in more aggressive disease states, such as patients with cytogenetic high-risk disease or patients ineligible for transplantation. We aimed to assess lenalidomide maintenance versus observation in patients with newly diagnosed multiple myeloma, including cytogenetic risk and transplantation status subgroup analyses. METHODS: The Myeloma XI trial was an open-label, randomised, phase 3, adaptive design trial with three randomisation stages done at 110 National Health Service hospitals in England, Wales, and Scotland. There were three potential randomisations in the study: induction treatment (allocation by transplantation eligibility status); intensification treatment (allocation by response to induction therapy); and maintenance treatment. Here, we report the results of the randomisation to maintenance treatment. Eligible patients for maintenance randomisation were aged 18 years or older and had symptomatic or non-secretory multiple myeloma, had completed their assigned induction therapy as per protocol and had achieved at least a minimal response to protocol treatment, including lenalidomide. Patients were randomly assigned (1:1 from Jan 13, 2011, to Jun 27, 2013, and 2:1 from Jun 28, 2013, to Aug 11, 2017) to lenalidomide maintenance (10 mg orally on days 1-21 of a 28-day cycle) or observation, and stratified by allocated induction and intensification treatment, and centre. The co-primary endpoints were progression-free survival and overall survival, analysed by intention to treat. Safety analysis was per protocol. This study is registered with the ISRCTN registry, number ISRCTN49407852, and clinicaltrialsregister.eu, number 2009-010956-93, and has completed recruitment. FINDINGS: Between Jan 13, 2011, and Aug 11, 2017, 1917 patients were accrued to the maintenance treatment randomisation of the trial. 1137 patients were assigned to lenalidomide maintenance and 834 patients to observation. After a median follow-up of 31 months (IQR 18-50), median progression-free survival was 39 months (95% CI 36-42) with lenalidomide and 20 months (18-22) with observation (hazard ratio [HR] 0·46 [95% CI 0·41-0·53]; p

Objective: To conduct an audit of the frequency of red cell concentrate transfusions (RCeTs) in infants of different weight categories, the donor exposure rate (DER) in these transfused infants and the volume of blood wasted during each transfusion, and to identify from this baseline information specific categories of infants who would benefit from the introduction of a limited donor exposure programme (LDEP). Study setting: Neonatal wards and neonatal intensive care unit (NICU), Tygerberg Hospital, Western Cape. Study design: A prospective descriptive study and comparison with a historic control group. Subjects: Information on the birth weight, age at the time of each RCCT and number of blood donors to whom an infant was exposed were collected post factum for all infants admitted to the neonatal wards and NICU between May 1993 and May 1994. During this time, the red blood cell concentrate was supplied as single paediatric bags (180 ml) transfused within 14 days of donation. An LDEP was introduced in February 1995. With this system, red blood cells were supplied as triple packs: a main unit of 250 ml with three empty satellite packs allowing up to three separate transfusions. These were assigned to a specific infant and were to be transfused within 21 days of donation. A second system where one adult blood bag was divided into two 180 ml bags and assigned to one infant to be transfused within 35 days of donation was also assessed. Results: Of the 7 854 infants admitted during the first 12-month audit period, 387 (4.9%) received 977 RCCTs. Of these, 183 (47.3%) received one transfusion, 72 (18.6%) two transfusions, 51 (13.2%) three transfusions, 27 (7.0%) four transfusions and 54 (13.9%) five or more transfusions. Infants (N = 188) with a birth weight beiow 1 500 g admitted to the NICU were identified as the group with the highest prevalence of RCCTs (68.6%), and it was therefore decided that in the prospective study such infants would qualify for the LDEP. A total of 81 infants was transfused with either the doubie (N = 47) or the triple bags (N = 34) over a 5-month period. The decrease in the mean OER (± SO) was clinically significant when the triple (1.9 ± 0.8) (P =0.0001) and the double bags (1.6 ± 0.8) (P =0.0001) were compared with the previous single-bag system (4.4 ± 3.5). Of concern was the large mean volume of concentrated red cells (118.5 ± 12.5 ml) wasted per transfusion with the single-bag system. Conclusions: This survey confinned a high RCCT rate as well as a very high DER in very-Iow-birth-weight (VLBW) infants treated at a tertiary centre. By assigning a triple or double bag of red cells from one blood donor and extending the storage of blood for small-volume RCCTs in infants from 14 days to 35 days, donor exposure was reduced significantly. We urge the introduction of the multibag blood transfusion system and extended storage period of blood for small-volume RCCT for VLBW infants in South Africa.S Afr Med J 1996: 86: 1460-1464

Contains fulltext : 219689.pdf (Publisher’s version ) (Open Access) On 7-8th November 2016, 60 people with an interest in the 'Trials within Cohorts' (TwiCs) approach for randomised controlled trial design met in London. The purpose of this 2nd TwiCs international symposium was to share perspectives and experiences on ethical aspects of the TwiCs design, discuss how TwiCs relate to the current ethical framework, provide a forum in which to discuss and debate ethical issues and identify future directions for conceptual and empirical research. The symposium was supported by the Wellcome Trust and the NIHR CLAHRC Yorkshire and Humber and organised by members of the TwiCs network led by Clare Relton and attended by people from the UK, the Netherlands, Norway, Canada and USA. The two-day symposium enabled an international group to meet and share experiences of the TwiCs design (also known as the 'cohort multiple RCT design'), and to discuss plans for future research. Over the two days, invited plenary talks were interspersed by discussions, posters and mini presentations from bioethicists, triallists and health research regulators. Key findings of the symposium were: (1) It is possible to make a compelling case to ethics committees that TwiCs designs are appropriate and ethical; (2) The importance of wider considerations around the ethics of inefficient trial designs; and (3) some questions about the ethical requirements for content and timing of informed consent for a study using the TwiCs design need to be decided on a case-by-case basis. 3 p.

We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4–1.0%), 2.3% (95% CI 1.6–2.7%) and 3.8% (95% CI 2.9–4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2–26.4%), compared with 6.5% (95% CI 0.2–12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.