Publications by authors named "Ray Powles"

Any conflict in countries that process nuclear power plants raises concerns of the potential radiation injuries to the people in that region and beyond such as the current conflict in Ukraine. International healthcare organizations and societies should prepare for the potential scenarios of nuclear incidents. The Worldwide Network for Blood and Marrow Transplantation (WBMT) and its members, have recent experience preparing for this type of events such as the Fukushima incident in 2011.

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Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting.

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Background Daratumumab (Darzalex) is a human IgG1 kappa monoclonal antibody targeting CD38 that has been recently approved for the treatment of refractory multiple myeloma. As it is a monoclonal protein, it can be detected on routine serum protein electrophoresis and by immunofixation. Methods Serum samples from four patients were analysed by serum protein electrophoresis immediately pre- and post-treatment with daratumumab.

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Objective: Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with ≥ 1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence.

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Objectives: The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature.

Methods: English-language articles were identified in MEDLINE and PubMed.

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We provide an overview on soft-tissue extramedullary plasmacytomas (EMPs) in multiple myeloma (MM). We reviewed the incidence of EMPs in MM, myeloma bone marrow homing, possible mechanisms of extramedullary spread, and prognosis and response to therapy. The incidence of EMPs is 7% to 18% at MM diagnosis and up to 20% at relapse.

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The European Blood and Marrow Transplantation Society's Nuclear Accident Committee has been a catalyst in bringing together consensus on the triage, Service Configuration, and care that might effectively be given by haematologists in the event of a massive irradiation incident. Further coordinated and integrated effort will be needed at European, international, and national levels to allow unified guidelines to treat such patients. The role of the training haematologist and devising a European Network of effective Service Configuration is the key to delivering an effective response if a major incident occurred.

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Lenalidomide in multiple myeloma.

Expert Rev Anticancer Ther

November 2009

Treatment options for patients have increased over the last few years, especially with the availability of novel agents for routine care and within clinical trials. Owing to the promising activity seen with lenalidomide in the relapsed/refractory setting, its use has now expanded to induction and maintenance therapy. It is generally well tolerated and the side effects, including hematological toxicity and thromboembolic complications, are usually easily managed.

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The concern of the public regarding terrorist actions involving nuclear emergencies resulted in the reopening of the discussion regarding the best ways to cope with the inevitable health impairments. Medical experts from the US and from Europe considered it of importance to harmonize at an international level the diagnostic and therapeutic approaches regarding the radiation-induced health impairments. The present contribution is the result of the first U.

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One-hundred-twenty consecutive adult patients aged 15-69 years (median 40) with acute myeloid leukemia (AML) excluding t(15;17) received induction therapy comprising idarubicin, high-dose cytarabine and etoposide. Planned post-induction treatment included two courses of moderate-intensity consolidation therapy followed by stem cell transplantation. 11 patients (9%) died during induction therapy.

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The aim of the study was to evaluate whether adequate stem cells (CD34+) could be harvested at presentation in myeloma patients such that high dose melphalan (HDM) with autologous stem cell rescue can be offered as primary therapy. The regimes either involved no prior cytoreductive chemotherapy (steroids only, n = 31) or a single course of VAD (n = 22). The median number of CD34 cells collected with steroids was 1.

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The epidemiology of plasma cell dyscrasias clearly links to a complicated multi-factorial pathogenic pathway that at the individual patient level gives no clear indication of why the malignant process has occurred but factors in the environment and within the genome give clues and are discussed. MGUS is a pre-malignant disorder characterised by monoclonal plasma cell proliferation in the bone marrow and no end-organ damage; the patients are asymptomatic. Primary amyloidosis is a rare disorder that is characterised by deposition of amyloid fibrils composed of immunoglobulin light chain fragments; symptoms relate to the affected organ.

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We report an analysis of the value of a second high-dose melphalan autograft, performed at relapse, on a series of newly diagnosed myeloma patients entered into the high-dose program at our center. We conclude that relapse-free survival after the first autograft is a major prognostic factor in determining outcome.

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If standard infusional therapy (IC) has been used to treat myeloma at presentation, it is a matter of debate whether patients should receive the original induction therapy or a different drug combination in first relapse. Instinctively, most clinicians may switch treatment, particularly since the advent of new drugs for the treatment of myeloma. Hitherto, there has been no data on the efficacy of repeating standard IC in the salvage setting.

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Purpose: To develop 2D 1H-MRS measurement sequences for the evaluation of bone marrow lipids, and to assess these measurement sequences in healthy and diseased bone marrow.

Materials And Methods: Single-voxel localized variants of COSY and DQF-COSY 2D 1H-MRS sequences were developed for use at 1.5 T to investigate the biochemical composition of human bone marrow in vivo.

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Induction chemotherapy followed by high-dose melphalan (HDM) is the standard treatment for fitter patients with myeloma. The place of bortezomib and the thalidomide analogues within this treatment paradigm is yet to be established. We sought to identify patients who may benefit from the introduction of novel agents during their initial management.

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We undertook a randomised prospective observational study to identify the true prevalence of dermatological problems on an acute in-patient haemato-oncology unit treating patients with myeloma and leukaemia (median age 52 years), that could be used to plan for optimum dermatological servicing of such a unit. As a snap-shot, beds were randomly selected each week and the patients in them examined to identify the prevalence and identity of mucocutaneous problems for in-patients. Primary endpoints were the prevalence of integument reactions, prevalence and type of rash.

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Multiple myeloma is a malignant disease of plasma cells that manifests as one or more of lytic bone lesions, monoclonal protein in the blood or urine, and disease in the bone marrow. Treatment for myeloma has changed beyond recognition in the past decade, and now includes state of the art supportive treatment and infusional chemotherapy courses, followed for younger patients by high-dose melphalan and an autologous transplant. Patients younger than 70 years can now expect a doubling of median survival to 5 years, a 20% chance of surviving longer than 10 years, and a 50% chance of attaining complete morphological and biochemical remission.

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Unlabelled: The Philadelphia chromosome translocation (Ph(+)) confers a poor prognosis in patients with acute lymphocytic leukemia (ALL). CD19 is highly expressed (CD19(+)) on ALL cells and is an attractive target for antibody-based therapies. CLB-CD19 is an IgG1kappa murine monoclonal antibody (mAb) directed against an epitope on the CD19 antigen.

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Background And Objectives: Disruption of either the p14ARF- mdm2- p53 or p16INK4A- Rb1 pathways produces a breakdown of regulatory mechanisms and creates a gateway for tumorigenesis. Since the incidence and clinical implications of abnormalities of TP53, CDKN2A (encoding for p16 and p14) and MDM2 genes (chromosome 12) in multiple myeloma (MM) is not clear, we investigated allelic loss at the former two loci and gain at the latter locus in a series of 82 MM patients.

Design And Methods: Dual color fluorescence in situ hybridization (FISH) was applied to bone marrow samples to establish the incidence of changes at the above mentioned loci.

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Purpose: Many attempts have been made to improve the results of allogeneic bone marrow transplantation (alloBMT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). Bone marrow cell dose has been reported to be an important factor in alloBMT; however, its true impact on relapse incidence (RI), leukemia-free survival (LFS), and nonrelapse mortality (NRM) in a large cohort of patients is unknown.

Patients And Methods: From January 1992 to December 1999, 572 bone marrow transplantation recipients reported to the European Blood and Marrow Transplantation (EBMT) registry underwent allografting from an HLA-identical sibling donor with an unmanipulated bone marrow for AML in CR1.

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Extending the principle of conventional acute lymphoblastic leukemia (ALL) therapy to transplantation, 77 adult patients receiving autografts in first remission after melphalan with or without total body irradiation were scheduled to receive 6-mercaptopurine (6MP), methotrexate (MTX), and vincristine-prednisone (VP) for 2 years after transplantation to reduce relapse. Seventy-one percent of patients received 6MP, 57% received MTX, and 38% received VP. Thirty patients had a relapse at 1.

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