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Leeds, United Kingdom

The survival prospects of critically ill patients with haematological malignancy (HM) are reviewed, as are the variables which might influence decisions about the limitation of life sustaining therapies (LLST). Approximately 40% of patients with HM admitted to ICU survive to hospital discharge and a broad admission policy is warranted. Short term survival is predicted by the severity of the underlying physiological disturbance rather than cancer specific characteristics, although the prognostic importance of neutropenia and prior stem cell transplantation remains to be clarified. Survival to hospital discharge in cancer patients following cardio-pulmonary resuscitation (CPR) is only 6-8%. Poor performance status and progressive deterioration despite ICU support appear to predict worse outcome. Patients should be provided with realistic information in order to make an informed decision about CPR. Decisions about LLST must be individualised. Consideration should be given to the patient's wishes and prognosis, the immediate clinical circumstances and their potential reversibility. © 2009 Elsevier Ltd. All rights reserved. Source


In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10-5). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10-4) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10-6). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.Leukemia advance online publication, 29 January 2016; doi:10.1038/leu.2015.313. © 2015 Macmillan Publishers Limited Source


Bowen D.T.,St Jamess Institute Of Oncology
Best Practice and Research: Clinical Haematology | Year: 2013

The myelodysplastic syndromes (MDS) are morphologically and genetically heterogeneous, and as such a single etiological factor is implausible. Therapy-related MDS has a clear etiology but the predisposition factors remain unclear. Most MDS (>90%) is not therapy-related and an etiology for this majority of patients, and indeed of better defined (morphological or genetic) subgroups cannot yet be ascertained. Exposure to occupational and environmental toxins is not obviously a major etiological contributor. The exceptions may be exposure to low concentrations of benzene and to tobacco smoke (which contains benzene amongst other carcinogens), but even these xenobiotics produce only modestly increased Hazard ratios for the development of MDS. It seems likely that low penetrance genetic variants may influence predisposition, and these may include pathways for xenobiotic metabolism, DNA repair and other quantitative trait loci.© 2013 Elsevier Ltd. All rights reserved. Source


Owen R.G.,St Jamess Institute Of Oncology
Clinical lymphoma, myeloma & leukemia | Year: 2011

Histological transformation, typically to diffuse large B-cell lymphoma (DLBCL) is reported to occur in 5%-10% of patients with WM and recent studies have highlighted a possible aetiological role for the nucleoside analogues. It is however becoming increasingly clear that histological transformation is a complex phenomenon and may include clonally unrelated disorders. In order to highlight this pathological heterogeneity we describe 5 patients with diverse histological progression events. These included EBV-associated events namely DLBCL, peripheral T-cell lymphoma and spontaneously resolving mucocutaneous ulcer. A further 2 patients demonstrated a localised plasma cell rich lesion simulating plasmacytoma and a de novo DLBCL arising in an unrelated B-cell clone. It is clear therefore that detailed pathological assessments are required in all suspected cases of transformation and that the pathological heterogeneity demonstrated by this study needs to be taken into account when potential aetiological factors are being assessed. Copyright © 2010 Elsevier Inc. All rights reserved. Source


Feyler S.,University of Leeds | Selby P.J.,University of Leeds | Cook G.,University of Leeds | Cook G.,St Jamess Institute Of Oncology
Blood Reviews | Year: 2013

An effective immune response requires a prompt but measured action against the pathological insult, to prevent over-zealous inflammatory-mediated tissue destruction. In cancer, defective or incompetent immune responses may paradoxically result in disease progression despite an immune attempt at elimination. Tumour-induced immunosuppression may not only result from soluble factors and altered antigenicity, but also from cellular-mediated tumour-induced immune evasion. Multiple myeloma (MM) is associated with both cellular and humoral immune deficiencies and increased TReg cells. In vitro modelling has indicated that the tumour cells directly induce functional TReg cells. In light of this recent evidence, it now seems that the most promising and synergistic approaches for cancer immunotherapy would involve specific anti-tumour immunity and simultaneous reduction of tumour-induced immune-regulation. This review sets out the basic understanding of the human immune response, its dysregulation in cancer and proposes how this knowledge may influence future treatment strategies to maximise the anti-tumour immune response. © 2013 Elsevier Ltd. Source

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