Christopher Dalley

A retrospective comparison of conventional intensity conditioning and reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis.

A retrospective comparison of conventional intensity conditioning and reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis

Guidelines for the diagnosis and management of adult myelodysplastic syndromes.

Sally B. Killick, Chris Carter, Dominic Culligan, Christopher Dalley, Emma Das-Gupta, Mark Drummond, Helen Enright, Gail L. Jones, Jonathan Kell, Juliet Mills, Ghulam Mufti, Jane Parker, Kavita Raj, Alexander Sternberg, Paresh Vyas, David Bowen and British Committee for Standards in Haematology The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, Hull and East Yorkshire Hospitals NHS Trust, Hull, Aberdeen Royal Infirmary, Aberdeen, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, Nottingham University Hospitals NHS Trust, Nottingham, Beatson West of Scotland Cancer Centre, Glasgow, UK, Tallaght Hospital Dublin, Trinity College Medical School, Dublin, Ireland, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, University Hospital of Wales, Cardiff, Worcestershire Acute Hospitals NHS Trust and Birmingham NHS Foundation Trust, Birmingham, Kings College Hospital NHS Foundation Trust, London, Northampton General Hospital NHS Trust, Northampton, Guys and St Thomas’ and Kings College Hospitals NHS Foundation Trusts, London, Great Western Hospitals NHS Foundation Trust, Swindon, Oxford University and Oxford University Hospitals NHS Trust, Oxford, and St. James’s Institute of Oncology, Leeds Teaching Hospitals, Leeds, UK

Acute myeloid leukaemia with associated eosinophilia: justification for FIP1L1‐PDGFRA screening in cases lacking the CBFB‐MYH11 fusion gene

Jean-Christophe Ianotto Jean-Jacques Kiladjian Jean-Louis Demory Lydia Roy Françoise Boyer Jerôme Rey Brigitte Dupriez Christian Berthou Jean-François Abgrall Service d’Hématologie clinique, Institut de Cancéro-Hématologie, CHU, Hôpital Morvan, Brest, Service d’Hématologie clinique, Assistance publique-Hôpitaux de Paris, Bobigny, Département d’Hématologie, Hôpital Saint-Vincent, Lille, Département d’OncoHématologie et de Thérapie cellulaire, CHU La Milétrie, Poitiers, Service des Maladies du Sang, CHU, Angers, Département d’Onco-Hématologie, Institut Paoli-Calmettes, Marseille, Service d’Hématologie clinique, CH, Lens, and Laboratoire d’Hématologie, CHU, Hôpital de la CavaleBlanche, Brest, France. E-mail: jcianotto@hotmail.com

The Uhthoff phenomenon : a potential post transplant complication in advanced progressive multiple sclerosis

The Uhthoff phenomenon: a potential post transplant complication in advanced progressive multiple sclerosis

Long-term dual donor derived haematopoietic reconstitution following double unrelated cord blood transplantation – single unit dominance is not always the case

In the recent Cord Blood Special Issue of the British Journal of Haematology, several reviews discussed double unrelated cord blood transplantation in detail (Delaney et al, 2009; Fernandez, 2009; Gluckman, 2009). The reviews highlighted the ultimate haematopoietic dominance of one cord blood unit over the other. Single unit cord unit dominance occurs relatively early post-transplant in the majority of patients and appears to be universal within 1 year post-transplant, irrespective of the intensity of conditioning regimen (Barker et al, 2005; Ballen et al, 2007; Brunstein et al, 2007). Potential mechanistic aspects were also discussed, although the biological factors which determine the ‘winning’ cord unit remain unclear (Delaney et al, 2009; Gluckman, 2009). At odds with these observations, we describe a patient treated with double Umbilical Cord Blood (UCB) transplantation in which there was full donor hematopoietic reconstitution with substantial and sustained contributions from both UCB sources well beyond 1 year post-transplant. In March 2005, a 21-year-old Caucasian female was diagnosed with high risk acute promyelocytic leukaemia (white cell count 170 · 10/l). Cytogenetic and molecular analysis confirmed t(15:17) translocation with PML–RARA fusion gene. Despite intensive treatments [PETHEMA (Programa para el Estudio y Tratamiento de las Hemopatias Maligna) regimen, gemtuzumab ozogamicin, arsenic trioxide and idiarubicin], she remained persistently minimal residual disease (MRD) positive both in blood and bone marrow by real-time quantitative polymerase chain reaction (RQ-PCR). In November 2006, magnetic resonance imaging confirmed leptomeningeal enhancement consistent with central nervous system (CNS) disease, whilst bone marrow examination confirmed medullary relapse. Two cycles of salvage chemotherapy (high dose methotrexate with high dose cytarabine) achieved both complete haematological and molecular remission, and clearance of CNS disease. With no siblings available, repeated worldwide unrelated donor registry search failed to identify a suitable donor and two suitable mismatched UCB units were identified for the patient (HLA-A*0301, 2402; B*1518, 1801; Cw*0501, 0704; DRB1*0407, 1301; DQB1*0301/09, 0603). Unit A was an 3/8 allele match (A*0301, 2403; B*3501/42, -;Cw*0401/09N, -; DRB1*0407, 1301; DQB1* NT) with a nucleated cell dose 4Æ89 · 10/kg. Unit B was a 5/10 allele match (A*0301, 2402; B*3801, 3548; Cw*0702, 1203; DRB1*0407, 1301; DQB1*0302, 0603) with a nucleated cell dose 3Æ2 · 10/kg. The units were selected to be allele matched at the HLA-DRB1 locus and no more than two antigen mismatched at the HLA-A and B loci combined between both patient and units as well as between units. In February 2007, the patient underwent double UCB transplant after conditioning with cyclophosphamide 120 mg/ kg and total body irradiation (12 Gy) and alemtuzumab (total dose 100 mg). Additional radiotherapy (5Æ4 Gy in three fractions) was given to the cranium before the transplant. Neutrophil engraftment (>0Æ5 · 10/l on two consecutive days) occurred at day +44 and platelet engraftment (platelet count>20 · 10/l without platelet support) on day +67. There was no acute graft-versus-host disease or severe infective episodes. At 32 months post-transplant, the patient remained well. Bone marrow and peripheral blood RQ-PCR remained molecularly negative for the PML-RARA transcript. Donor chimerism was analysed using the Promega Powerplex 16 System (Promega, Madison, WI, USA), which co-amplifies 15 short tandem repeat loci and amelogenin, fluorescently detected on an abi prism 3730 system with GeneMapper software (Applied Biosystems, Foster City, CA,

Specialist integrated haematological malignancy diagnostic services: an Activity Based Cost (ABC) analysis of a networked laboratory service model

Aims Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) were introduced as a standard of care within the UK National Health Service to reduce diagnostic error and improve clinical outcomes. Two broad models of service delivery have become established: ‘co-located’ services operating from a single-site and ‘networked’ services, with geographically separated laboratories linked by common management and information systems. Detailed systematic cost analysis has never been published on any established SIHMDS model. Methods We used Activity Based Costing (ABC) to construct a cost model for our regional ‘networked’ SIHMDS covering a two-million population based on activity in 2011. Results Overall estimated annual running costs were £1 056 260 per annum (£733 400 excluding consultant costs), with individual running costs for diagnosis, staging, disease monitoring and end of treatment assessment components of £723 138, £55 302, £184 152 and £94 134 per annum, respectively. The cost distribution by department was 28.5% for haematology, 29.5% for histopathology and 42% for genetics laboratories. Costs of the diagnostic pathways varied considerably; pathways for myelodysplastic syndromes and lymphoma were the most expensive and the pathways for essential thrombocythaemia and polycythaemia vera being the least. Conclusions ABC analysis enables estimation of running costs of a SIHMDS model comprised of ‘networked’ laboratories. Similar cost analyses for other SIHMDS models covering varying populations are warranted to optimise quality and cost-effectiveness in delivery of modern haemato-oncology diagnostic services in the UK as well as internationally.

Treatment of relapsed myelodysplastic syndrome following double umbilical cord blood transplantation with interferon alpha and 5-azacytidine

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Long term lympho-haematopoietic reconstitution by umbilical cord blood stem cells following primary graft failure and autologous rescue.

fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood, 113, 4094–100. Risitano, AM, Seneca, E, Marando, L, Imbraco, M, Soscia, E, Soscia, F, Micol Pizzuti, L, Malcovati, L, Fenu, S, Iori, AP, Notaro, R, Matarazzo, M & Rotoli, B. (2009b) From renal siderosis due to perpetual hemosiderinuria to possible liver overload due to extravascular hemolysis: changes in iron metabolism in paroxysmal nocturnal hemoglobinuria (PNH) patients on eculizumab. Blood, 114, 4031 (abs). Risitano, AM, Perna, F & Selleri, C. (2011) Achievements and limitations of complement inhibition by eculizumab in paroxysmal nocturnal hemoglobinuria: the role of complement component 3. Mini Reviews in Medicinal Chemistry, 11, 528–35. Röth, A, Hock, C, Konik, A, Christoph, S & Dührsen, U. (2011) Chronic treatment of paroxysmal nocturnal hemoglobinuria patients with eculizumab: safety, efficacy, and unexpected laboratory phenomena. International Journal of Hematology, 93, 704–14.

Histopathological Response of Transitional Cell Carcinoma to Arsenic Trioxide during the Treatment of Concurrently Diagnosed Acute Promyelocytic Leukaemia

Sir d We enjoyed the recent review of the naturally occurring double-stranded RNA oncolytic reovirus by Comins et al. [1]. In addition to discussing the direct anticancer activity of reovirus, the authors mentioned the induction of an anti-viral humoral immune response as a limiting factor in virotherapy: high titres of neutralising antibody are rapidly generated in response to the systemic delivery of reovirus [2]. Considerable efforts are being made with a variety of oncolytic viruses to design methods of protecting viral particles from neutralisation within the circulation, including lipid encapsulation, polymer coating and cellular carriage; the success of these approaches may be critical to the future of oncolytic virotherapy. We wish to highlight the possibility that, in contrast to the antibody response, the cellular immune system may play a central role in mediating anti-tumour activity. In addition to direct oncolysis, oncolytic viruses may generate anti-tumour immunity or anti-viral cellular immune responses eliminating virally infected tumour cells. Reovirus infection of melanoma cells has been shown to result in the secretion of a range of pro-inflammatory cytokines and chemokines, including interleukin-8, RANTES, MIP-1a and MIP-1b [3]. These soluble mediators will act to recruit other cells of the immune system to the tumour microenvironment. Reovirus additionally directly activates dendritic cells [4], the professional antigen presenting cells of the immune system. The presence of ‘danger’ signals are required for the generation of an effective anti-tumour immune response [5]. Tumour infection by an oncolytic virus can powerfully provide such signals. In the case of reovirus, ‘danger’ signals may be provided by alterations in the tumour microenvironment, including cytokine secretion and innate immune cell infiltration, or the recognition of double-stranded RNA via the double-stranded RNA-dependent protein kinase or tolllike receptor 3 present within dendritic cells. Consistent with this concept is the finding that reovirus infection of both human and murine melanoma cell lines can generate adaptive anti-tumour immune responses [6]. Oncolytic virotherapy trials should be designed with specific assessment of both anti-viral and anti-tumour immune responses. An understanding of, and the ability to harness, the immunotherapeutic potential of these novel agents may be required for these novel agents to fulfil their maximum potential. In this regard, the outcome of planned studies combining reovirus with immunomodulation using cyclophosphamide will be intriguing.

Lessons from a Jehovah’s Witness with 5q‐ syndrome: role of systemic immunosuppression and kinetics of recovery with lenalidomide from a life threatening anaemia

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