MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'British Journal of Haematology' source. Wed, 08 Feb 2012 17:41:59 +0100 http://www.medworm.com/index.php?rid=5668090&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09031.x SummaryCyril Clarke was an outstanding general physician and lepidopterist. Late in his career, and stimulated by his work on the genetics of mimicry in butterflies, he became interested in the evolving field of medical genetics. His work on the relationship of blood groups to particular diseases led him and his team in Liverpool to evolve a remarkably successful approach to the prevention of Rhesus haemolytic disease of the newborn. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668090 Wed, 08 Feb 2012 05:00:00 +0100 5668090 http://www.medworm.com/index.php?rid=5668089&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09037.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668089 Wed, 08 Feb 2012 05:00:00 +0100 5668089 http://www.medworm.com/index.php?rid=5668088&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09038.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668088 Wed, 08 Feb 2012 05:00:00 +0100 5668088 http://www.medworm.com/index.php?rid=5668087&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09042.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668087 Wed, 08 Feb 2012 05:00:00 +0100 5668087 http://www.medworm.com/index.php?rid=5668086&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09043.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668086 Wed, 08 Feb 2012 05:00:00 +0100 5668086 http://www.medworm.com/index.php?rid=5668085&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09048.x SummaryCD34‐selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft‐versus‐host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post‐transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34‐selected 8–10/10 human leucocyte antigen (HLA)‐matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n = 13) or non‐malignant (... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668085 Wed, 08 Feb 2012 05:00:00 +0100 5668085 http://www.medworm.com/index.php?rid=5668084&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09027.x SummaryBurkitt lymphoma (BL) was first described in Uganda in 1958 as a sarcoma of the jaw but later confirmed to be a distinct form of Non Hodgkin lymphoma (NHL). This discovery was the defining moment of cancer research in Uganda, which eventually led to the establishment of a dedicated cancer research institute, the Uganda Cancer Institute (UCI) in 1967. The centre was dedicated to Denis Burkitt in recognition of his contribution to cancer research in East Africa. BL is still the commonest NHL in childhood in Uganda. Its incidence has significantly increased recently due to yet unknown factors. Although the human immunodeficiency virus (HIV) was considered a possible reason for the increase, there is no evidence that it has substantially impacted on the epidemiology of the disease. Howe... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668084 Wed, 08 Feb 2012 05:00:00 +0100 5668084 http://www.medworm.com/index.php?rid=5668083&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09045.x SummaryDenis Parsons Burkitt, surgeon and research scientist, is a household name in the medical profession. Denis received his BA in 1933 and graduated as a physician in 1935 from Trinity College, Dublin. After serving as a surgeon in the Royal Army Medicine Corps during World War II, he worked as a surgeon and lecturer in Africa. It was in Africa that he developed exceptional observational and analytical skills, which led him to identify and formally develop a successful treatment for a childhood cancer that is now called Burkitt Lymphoma. The influence of Christianity in his life was huge. Throughout his life he remained extremely modest, attributing much of what he had achieved to the work of others. Denis's contributions to haemato‐oncology remain salient today, and his discoveries ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668083 Wed, 08 Feb 2012 05:00:00 +0100 5668083 http://www.medworm.com/index.php?rid=5668092&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09044.x SummaryThe intra‐erythrocyte growth and survival of the malarial parasite Plasmodium falciparum is responsible for both uncomplicated and severe malaria cases and depends on the parasite's ability to remodel its host cell. Host cell remodelling has several functions for the parasite, such as acquiring nutrients from the extracellular milieu because of the loss of membrane transporters upon erythrocyte differentiation, avoiding splenic clearance by conferring cytoadhesive properties to the infected erythrocyte, escaping the host immune response by exporting antigenically variant proteins at the red blood cell surface. In addition, parasite‐induced changes at the red blood cell membrane and sub‐membrane skeleton are also necessary for the efficient release of the parasite progeny from ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668092 Tue, 07 Feb 2012 05:00:00 +0100 5668092 http://www.medworm.com/index.php?rid=5668091&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09046.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668091 Tue, 07 Feb 2012 05:00:00 +0100 5668091 http://www.medworm.com/index.php?rid=5649206&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09034.x This study analysed the effects of growth factor on outcome after haematopoietic stem‐cell transplantation (HSCT) with >9 years follow‐up. Of 1887 adult patients with acute leukaemia who received bone marrow from human leucocyte antigen (HLA)‐identical siblings and were treated with myeloablative conditioning, 459 (24%) were treated with growth factor. Growth factor hastened engraftment of neutrophils (P < 0·0001), but reduced platelet counts (P = 0·0002). Graft‐versus‐host disease (GVHD)‐free survival (no acute GVHD grade II–IV or chronic GVHD) at 10 years was 12 ± 2% (±SE) in the growth factor group, as opposed to 17 ± 2% in the controls [hazard ratio (HR) 0·81, P = 0·001]. Similar differences in GVHD‐free survival were seen in patients with or wi... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649206 Thu, 02 Feb 2012 05:00:00 +0100 5649206 http://www.medworm.com/index.php?rid=5649205&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09039.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649205 Thu, 02 Feb 2012 05:00:00 +0100 5649205 http://www.medworm.com/index.php?rid=5668082&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09055.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5668082 Wed, 01 Feb 2012 05:00:00 +0100 5668082 http://www.medworm.com/index.php?rid=5649214&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09036.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649214 Wed, 01 Feb 2012 05:00:00 +0100 5649214 http://www.medworm.com/index.php?rid=5649213&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09035.x SummaryDenis Burkitt's description of the eponymous lymphoma in 1958 in Uganda, opened up a vast and important field of enquiry in haematology and oncology. His pioneering experiments with chemotherapy demonstrated the possibility of cure, often with a single dose. His geographical explorations showed the tumour to be delimited by climate, suggesting an infectious cause vectored by mosquitoes. His clinical observations furthered the field of cancer immunotherapy. And his collegial, inquisitive nature facilitated the development of an enduring cancer research centre in Kampala. Burkitt's legacy in Uganda has wide‐reaching effects that endure not only in Uganda but also throughout the haematology‐oncology community to this day. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649213 Wed, 01 Feb 2012 05:00:00 +0100 5649213 http://www.medworm.com/index.php?rid=5649212&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09032.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649212 Wed, 01 Feb 2012 05:00:00 +0100 5649212 http://www.medworm.com/index.php?rid=5649211&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09033.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649211 Wed, 01 Feb 2012 05:00:00 +0100 5649211 http://www.medworm.com/index.php?rid=5649210&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09029.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649210 Wed, 01 Feb 2012 05:00:00 +0100 5649210 http://www.medworm.com/index.php?rid=5649209&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09030.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649209 Wed, 01 Feb 2012 05:00:00 +0100 5649209 http://www.medworm.com/index.php?rid=5649208&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09026.x SummaryThe refinements in both the staging and response evaluation of children with Burkitt lymphoma (BL) have contributed to the improvements in treatment outcome observed over the past 40 years. Ziegler and Magrath designed a staging system in the 1970s for children with BL in equatorial Africa. Currently, the most widely used staging system around the world is that described by Murphy in 1980, which was developed for children with non‐Hodgkin lymphoma (NHL) of any histology. There are opportunities for refinement in this system, particularly with respect to certain extra‐nodal sites, such as skin and bone. The findings obtained at diagnosis with novel technologies (functional imaging [e.g., positron emission tomography [PET]] and minimal residual disease [MRD] technology), which ar... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649208 Wed, 01 Feb 2012 05:00:00 +0100 5649208 http://www.medworm.com/index.php?rid=5649207&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09028.x SummaryTransient myeloproliferative disorder (TMD) of the newborn and acute megakaryoblastic leukaemia (AMKL) in children with Down syndrome (DS) represent paradigmatic models of leukaemogenesis. Chromosome 21 gene dosage effects and truncating mutations of the X‐chromosomal transcription factor GATA1 synergize to trigger TMD and AMKL in most patients. Here, we report the occurrence of TMD, which spontaneously remitted and later progressed to AMKL in a patient without DS but with a distinct dysmorphic syndrome. Genetic analysis of the leukaemic clone revealed somatic trisomy 21 and a truncating GATA1 mutation. The analysis of the patient's normal blood cell DNA on a genomic single nucleotide polymorphism (SNP) array revealed a de novo germ line 2·58 Mb 15q24 microdeletion including 41 ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649207 Wed, 01 Feb 2012 05:00:00 +0100 5649207 http://www.medworm.com/index.php?rid=5649204&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2012.09040.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5649204 Wed, 01 Feb 2012 05:00:00 +0100 5649204 http://www.medworm.com/index.php?rid=5639113&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09009.x In conclusion, a simple model which includes: age, JAK2 V617F‐status and constitutional symptoms can clearly separate distinct risk groups and can be used in addition to the Lille model to predict OS after RIC‐ASCT for myelofibrosis. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5639113 Sun, 29 Jan 2012 21:56:57 +0100 5639113 http://www.medworm.com/index.php?rid=5610005&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09013.x SummaryThe two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria – BL incidence relates to the malaria transmission rate – and early infection by Epstein–Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component of lymphomagenesis in BL. The critical event in lymphomagenesis is the creation of a MYC translocation, bringing the MYC gene into juxtaposition with immunoglobulin genes and causing its ectopic expression, thereby driving the proliferation of BL cells. It is highly likely that such translocations are mediated by the activation‐induced cytidine deaminase (AID) gene, which is responsible for hypervariable region mutations as well as class switching. Stimulation... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5610005 Fri, 20 Jan 2012 21:51:02 +0100 5610005 http://www.medworm.com/index.php?rid=5610008&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09024.x SummaryBurkitt lymphoma/leukaemia is the most common (40%) form of non‐Hodgkin lymphoma that occurs in children and adolescents. The prognosis of advanced (disseminated) Burkitt lymphoma/leukaemia in children and adolescents three decades ago had a 5‐year event‐free survival (EFS) of <40%, and required combination chemotherapy and radiation therapy over a 1–2 year period. Currently, the prognosis for the same advanced stage has a 5‐year EFS of 85–90% with <6 months of chemotherapy only. Radiation therapy has been eliminated for children and adolescents with Burkitt lymphoma/leukaemia except in emergencies, such as superior vena cava syndrome and acute neurological impairment or in patients with relapse/progression. Current risk factors in the prognosis of childhood and ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5610008 Fri, 20 Jan 2012 05:00:00 +0100 5610008 http://www.medworm.com/index.php?rid=5610007&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09015.x In conclusion, 4‐HNE transfer from pRBCs to npRBCs in rosettes is suggested to play a role in the phagocytic removal of large numbers of npRBCs, the hallmark of severe malaria anaemia. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5610007 Fri, 20 Jan 2012 05:00:00 +0100 5610007 http://www.medworm.com/index.php?rid=5598788&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09025.x We presented here the first GWAS for plasma AT and free‐PS levels and ACV in Caucasian samples. We identified three independent loci associated with ACV (F2, F5 and PROCR) and replicated two independent effects on plasma PC levels at the PROCR locus. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5598788 Tue, 17 Jan 2012 22:46:53 +0100 5598788 http://www.medworm.com/index.php?rid=5598793&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09023.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5598793 Mon, 16 Jan 2012 05:00:00 +0100 5598793 http://www.medworm.com/index.php?rid=5598792&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09007.x SummaryThe particular epidemiological features of Burkitt lymphoma (BL) in Tropical Africa, first described by Denis Burkitt in 1958, initiated the search for a virus that induces malignant B cell lymphomas in humans and is transmitted by arthropods. The herpes virus (Epstein‐Barr virus, EBV) discovered by Epstein and collaborators in cell lines established from BL biopsies fulfilled some of these predictions. It drives primary B cells into unlimited proliferation, induces malignant B cell lymphomas in immunocompromised individuals (post‐transplant lympho‐proliferative disease, PTLD) in vivo, and footprints of the virus are generally detected in African BL biopsies supporting a causative role of the virus in the pathogenesis of BL. The virus is, however, not transmitted by arthropods... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5598792 Mon, 16 Jan 2012 05:00:00 +0100 5598792 http://www.medworm.com/index.php?rid=5598791&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09011.x SummaryThe majority of patients with diffuse large B‐cell lymphoma are over the age of 60 years and the management of these patients is often sub‐optimal. Intensive therapy with curative intent should be given to all patients who can tolerate such therapy, and this requires very careful evaluation of each patient prior to treatment allocation. A detailed history and examination are required, with attention to concomitant disease and existing drug therapy. A quantitative assessment of comorbidity and a comprehensive geriatric assessment (CGA) are valuable adjuncts to physician judgment. For most elderly patients, the R‐CHOP regimen (rituximab, cyclophosphamide doxorubicin, vincristine, prednisolone) remains the standard of care. Granulocyte colony‐stimulating factor should be give... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5598791 Mon, 16 Jan 2012 05:00:00 +0100 5598791 http://www.medworm.com/index.php?rid=5598790&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09012.x The objective of this guideline is to provide healthcare professionals with clear and simple recommendations for the diagnosis, treatment and prevention of iron deficiency in pregnancy and the postpartum period. This is the first such guideline in the UK and may be applicable to other developed countries. Public health measures, such as helminth control and iron fortification of foods, which can be important to developing countries, are not considered here. The guidance may not be appropriate to all patients and individual patient circumstances may dictate an alternative approach. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5598790 Mon, 16 Jan 2012 05:00:00 +0100 5598790 http://www.medworm.com/index.php?rid=5598789&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09021.x This study aimed to identify signalling pathways responsible for this segregation. Gel‐filtered platelets, intact or loaded with calcium‐sensitive dyes, were activated and labelled with annexin V and antibodies, followed by flow cytometric analysis. Calcium Green and Fura Red dyes were compared, and only the latter was able to detect calcium level differences in the platelet subpopulations. Phosphatidylserine‐positive platelets produced by thrombin had stably high intracellular calcium level; addition of convulxin increased and stabilized calcium level in the phosphatidylserine‐negative subpopulation. PAR1 agonist SFLLRN also induced calcium rise and subpopulation formation, but the resulting platelets were not coated with alpha‐granule proteins. Adenylatecyclase activator forsko... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5598789 Mon, 16 Jan 2012 05:00:00 +0100 5598789 http://www.medworm.com/index.php?rid=5583353&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08996.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583353 Sat, 14 Jan 2012 07:23:03 +0100 5583353 http://www.medworm.com/index.php?rid=5583352&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09006.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583352 Sat, 14 Jan 2012 07:23:01 +0100 5583352 http://www.medworm.com/index.php?rid=5583329&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08986.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583329 Sat, 14 Jan 2012 07:20:11 +0100 5583329 http://www.medworm.com/index.php?rid=5583335&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09003.x SummaryEast Africa was at the forefront of early achievements and discoveries in paediatric oncology thanks to Denis Burkitt’s seminal work. Although these successes have been built upon and continued elsewhere, they were sadly not sustained in sub‐Saharan Africa for a variety of reasons. In recent years however this situation is slowly changing in countries across the continent. Tanzania is one such African country. Until very recently, survival rates of 5–10% for all children’s cancers were expected. However, change has been brought about thanks to the combined efforts and commitments of the Tanzanian Ministry of Health, non‐governmental organizations – such as The International Network for Cancer Treatment and Research and Children in Crossfire – and the participation of t... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583335 Wed, 11 Jan 2012 05:00:00 +0100 5583335 http://www.medworm.com/index.php?rid=5583334&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09008.x SummaryThe chance germinal encounter with the first lecture outside Africa on Burkitt lymphoma is described together with the hypothesis of a viral cause. Repeated virological investigations on lymphoma biopsies proved negative, leading to the idea that a latent virus might be activated if lymphoma cells could be cultured, although no human lymphoid cell had at that time ever been maintained in vitro. A chance event reminding of the need for suspension culture with mouse lymphomas led to success. The cultured cells carried a morphologically unequivocal, strangely inert, herpesvirus shown later to be immunologically, biologically and biochemically unique. How this new agent acquired its name, Epstein–Barr virus, is explained. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583334 Wed, 11 Jan 2012 05:00:00 +0100 5583334 http://www.medworm.com/index.php?rid=5583333&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09017.x SummaryDenis Parsons Burkitt was born in 1911, and in the late 1950s, described the disease that has come to be known as Burkitt lymphoma based on cases he observed in Uganda. Subsequently, Burkitt lymphoma was recognized as the first human tumour associated with an infectious agent when Epstein–Barr virus was isolated from samples supplied by Burkitt. It is now recognized that over one‐quarter of cancers worldwide are tied to infections. Notably, liver cancer is linked to hepatitis B virus and hepatitis C virus infections, and cervical cancer to infections involving the human papilloma viruses. In addition, immunocompromise arising from infection with the human immunodeficiency virus allows tumours (e.g., Kaposi sarcoma) caused by other viruses to arise. More than 50 years after the... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583333 Wed, 11 Jan 2012 05:00:00 +0100 5583333 http://www.medworm.com/index.php?rid=5583332&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09018.x This study examined the risk of recurrent venous thromboembolism (VTE) in patients with elevated albuminuria. In 1997–1998, inhabitants of Groningen, the Netherlands, aged 28–75 years (n = 85 421), were invited to participate in the PREVEND (Prevention of REnal and Vascular ENd stage Disease) Study, an observational, population‐based cohort study. Albuminuria was measured and VTE occurrence was monitored in responding subjects (n = 40 856). Patients with first VTE between study entry and January 2009, identified through databases of the national registry of hospital discharge diagnoses, death certificates, regional anticoagulation clinic and medical records, were used for analysis. Of 351 subjects with first VTE, 37 subjects developed a recurrence during a median follow... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583332 Wed, 11 Jan 2012 05:00:00 +0100 5583332 http://www.medworm.com/index.php?rid=5583331&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09020.x SummarySince July 2008, children and adults 1–45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared with historical controls, we performed a retrospective national population‐based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15–91 years). The 5‐year projected event‐free survival (pEFS5y) and overall survival (pOS5y) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4–33·6] and 34·1% (95%... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583331 Wed, 11 Jan 2012 05:00:00 +0100 5583331 http://www.medworm.com/index.php?rid=5583330&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09022.x SummaryObservations in human tumours, as well as mouse models, have indicated that telomere dysfunction may be a key event driving genomic instability and disease progression in many solid tumour types. In this scenario, telomere shortening ultimately results in telomere dysfunction, fusion and genomic instability, creating the large‐scale rearrangements that are characteristic of these tumours. It is now becoming apparent that this paradigm may also apply to haematological malignancies; indeed these conditions have provided some of the most convincing evidence of telomere dysfunction in any malignancy. Telomere length has been shown in several malignancies to provide clinically useful prognostic information, implicating telomere dysfunction in disease progression. In these malignancies ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583330 Wed, 11 Jan 2012 05:00:00 +0100 5583330 http://www.medworm.com/index.php?rid=5583351&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08989.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583351 Mon, 09 Jan 2012 05:00:00 +0100 5583351 http://www.medworm.com/index.php?rid=5583350&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08990.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583350 Mon, 09 Jan 2012 05:00:00 +0100 5583350 http://www.medworm.com/index.php?rid=5583349&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08991.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583349 Mon, 09 Jan 2012 05:00:00 +0100 5583349 http://www.medworm.com/index.php?rid=5583348&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08992.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583348 Mon, 09 Jan 2012 05:00:00 +0100 5583348 http://www.medworm.com/index.php?rid=5583347&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08993.x SummaryAn intention‐to‐treat (ITT) analysis was performed in 103 unselected patients with relapsed/refractory classical Hodgkin lymphoma (CHL) comparing early relapse (<12 months) or failure of first‐line therapy (ER/FTF) with late relapses (LR). Seventy one percentage proceeded to high‐dose therapy/autologous stem cell rescue (HDT/ASCR) following salvage treatment. By ITT, 5‐year overall survival (OS) was 50% for ER/FTF compared to 73% for LR patients (P = 0·012). However OS was equivalent for both groups if salvage treatment response was adequate to proceed to HDT/ASCR. ER/FTF patients remain a high‐risk group largely due to a failure of salvage therapy: a point at which novel interventions could impact survival. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583347 Mon, 09 Jan 2012 05:00:00 +0100 5583347 http://www.medworm.com/index.php?rid=5583346&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08998.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583346 Mon, 09 Jan 2012 05:00:00 +0100 5583346 http://www.medworm.com/index.php?rid=5583345&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08999.x In conclusion, aggressive treatment may be warranted in patients experiencing ASSC before 2 years of age. Randomized controlled trials are needed to define the best treatment modalities. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583345 Mon, 09 Jan 2012 05:00:00 +0100 5583345 http://www.medworm.com/index.php?rid=5583344&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09000.x SummaryPatients with chronic lymphocytic leukaemia (CLL) whose tumour cells harbour a 17p deletion (17p‐) are universally considered to have a poor prognosis. The deletion can be detected at diagnosis or during the evolution of the disease, particularly in patients who have received chemotherapy. We sought to evaluate the natural history of patients with 17p‐ CLL, identify predictive factors within this prognostic subgroup, and evaluate the results of different therapeutic approaches. Data from 294 patients with 17p‐ CLL followed up at 20 different institutions was retrospectively collected and analysed. Median age was 68 (range 27–98) years at the time of fluorescence in situ hybridization analysis. After 17p‐ documentation, 52% received treatment, achieving an overall response ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583344 Mon, 09 Jan 2012 05:00:00 +0100 5583344 http://www.medworm.com/index.php?rid=5583343&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09001.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583343 Mon, 09 Jan 2012 05:00:00 +0100 5583343 http://www.medworm.com/index.php?rid=5583342&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09004.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583342 Mon, 09 Jan 2012 05:00:00 +0100 5583342 http://www.medworm.com/index.php?rid=5583341&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09005.x SummaryThis review will focus on the strengths and limitations associated with the current standard of care for primary prevention of ischaemic strokes in children with sickle cell anaemia (SCA) ‐ transcranial Doppler ultrasound (TCD) screening followed by regular blood transfusion therapy when TCD measurement is above a threshold defined by a randomized clinical trial (RCT). The theoretical basis for potential alternative strategies for primary prevention of neurological injury in SCA is also discussed. These strategies will include, but will not be limited to: immunizations to prevent bacterial infections, particularly in low income countries; management of elevated blood pressure; and targeted strategies to increase baseline haemoglobin levels with therapies such as hyroxycarbamide or... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583341 Mon, 09 Jan 2012 05:00:00 +0100 5583341 http://www.medworm.com/index.php?rid=5583340&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09010.x This study analysed 298 MBL patients by multi‐parameter flow cytometry, chromosome banding analysis (CBA)/fluorescence in situ hybridization (FISH), and IGHV mutation status and compared them with 356 CLL patients. In MBL, CBA more frequently revealed a normal karyotype and FISH identified less frequently del(6q), del(13q) (as sole alterations), and del(17)(p13). Within the MBL cohort, a shorter time to treatment (TTT) was found for ZAP‐70‐positivity, 14q32/IGH‐translocations (CBA), del(11)(q22·3) (FISH) and unmutated IGHV status. Higher CD38 and ZAP‐70 expression, del(11)(q22·3) (FISH), trisomy 12 (FISH), and 14q32/IGH‐translocations (CBA) were correlated with a shorter TTT in the combined cohort (MBL + CLL); a sole del(13)(q14) (FISH) correlated with longer TTT. Regardi... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583340 Mon, 09 Jan 2012 05:00:00 +0100 5583340 http://www.medworm.com/index.php?rid=5583339&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09014.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583339 Mon, 09 Jan 2012 05:00:00 +0100 5583339 http://www.medworm.com/index.php?rid=5583338&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09016.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583338 Mon, 09 Jan 2012 05:00:00 +0100 5583338 http://www.medworm.com/index.php?rid=5583337&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09019.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583337 Mon, 09 Jan 2012 05:00:00 +0100 5583337 http://www.medworm.com/index.php?rid=5583336&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08994.x SummaryUmbilical cord blood transplant (UCBT) is associated with impaired early immune reconstitution. This might be explained by a lower T‐cell dose infused, the naivety of cord blood T‐cells and the use of in vivo T‐cell depletion. We studied the pattern of early immune reconstitution and the clinical outcome of children undergoing unrelated UCBT when in vivo T‐cell depletion was omitted. Thirty children affected by malignancies (46%) or immunodeficiencies (54%) underwent an unrelated UCBT. Prospective assessment of immune reconstitution and clinical outcome was performed. We observed an unprecedented CD4+ T‐cell reconstitution, with a median cell count at 30 and 60 d post UCBT of 0·3 × 109/l and 0·56 × 109/l, respectively. Early T‐cell expansion was thymic‐in... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5583336 Mon, 09 Jan 2012 05:00:00 +0100 5583336 http://www.medworm.com/index.php?rid=5572798&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.09002.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5572798 Sun, 01 Jan 2012 05:00:00 +0100 5572798 http://www.medworm.com/index.php?rid=5561175&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08985.x We describe a minimal amplified segment within the so‐called ‘Down syndrome critical region’ shared between two cases of AML‐M0; a Down syndrome, and a constitutionally normal individual. Interestingly, the amplified region does not include the oncogenes RUNX1, ETS2 and ERG. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5561175 Sun, 01 Jan 2012 05:00:00 +0100 5561175 http://www.medworm.com/index.php?rid=5553037&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08976.x This study demonstrated that the novel combination of 2‐CDA/Ida was effective and should be considered for incorporation in front line therapy for children with AML. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5553037 Sat, 31 Dec 2011 19:54:11 +0100 5553037 http://www.medworm.com/index.php?rid=5538713&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08983.x In conclusion, we have identified potent anti‐myeloma activity for this novel HDAC inhibitor that gives further insights into the biological sequelae of HDAC inhibition in MM. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5538713 Sun, 25 Dec 2011 10:20:00 +0100 5538713 http://www.medworm.com/index.php?rid=5538716&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08979.x We report on 31 consecutive lower‐risk non‐del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion‐dependent (RBC‐TD) patients, who became transfusion‐independent (RBC‐TI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion‐free after 11+–31+ months. Median response duration was 24 months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN + ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC‐TI and... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5538716 Fri, 23 Dec 2011 05:00:00 +0100 5538716 http://www.medworm.com/index.php?rid=5538714&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08969.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5538714 Fri, 23 Dec 2011 05:00:00 +0100 5538714 http://www.medworm.com/index.php?rid=5526226&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08995.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5526226 Thu, 22 Dec 2011 10:22:42 +0100 5526226 http://www.medworm.com/index.php?rid=5526222&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08988.x SummaryMultidrug‐resistant viruses remain a clinically challenging complication in the immunocompromised host. This review discusses mechanisms of viral resistance and treatment options in this context with particular emphasis on the immunocompromised haematology patient. We also outline some of the newer agents and treatment strategies being developed to treat multidrug‐resistant viruses. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5526222 Thu, 22 Dec 2011 10:20:06 +0100 5526222 http://www.medworm.com/index.php?rid=5526223&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08987.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5526223 Thu, 22 Dec 2011 05:00:00 +0100 5526223 http://www.medworm.com/index.php?rid=5526225&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08975.x SummaryMost children and adolescents with newly diagnosed high‐risk Hodgkin lymphoma (HL) will achieve remission and cure with conventional chemotherapy with or without radiation therapy. However, these therapies can lead to long‐term side effects. Therapy is titrated on the basis of risk group stratification using clinical prognostic factors and, in most cases, then refined through assessment of interim or end of chemotherapy response, primarily using functional imaging with fluorodeoxyglucose positron emission tomography. No study has clearly demonstrated the factors that are sufficient in identifying the patients at highest risk for relapse that may benefit from therapy intensification. This review summarizes recent clinical trials in paediatric high‐risk HL, along with key findin... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5526225 Tue, 20 Dec 2011 05:00:00 +0100 5526225 http://www.medworm.com/index.php?rid=5526224&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08982.x In conclusion, ENKTL is more common and clinically more similar among Hispanics and APIs than non‐Hispanic whites with poor outcome in all racial groups. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5526224 Tue, 20 Dec 2011 05:00:00 +0100 5526224 http://www.medworm.com/index.php?rid=5516040&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08980.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5516040 Mon, 19 Dec 2011 10:13:05 +0100 5516040 http://www.medworm.com/index.php?rid=5506071&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08984.x SummaryOver‐expression of anti‐apoptotic BCL2 has been reported in chronic lymphocytic leukaemia (CLL), but targeting BCL2 alone did not yield appreciable clinical results. However, it was demonstrated that BCL2 inhibitors enhanced the clinical efficacy of chemo and immunotherapeutics. Lenalidomide, an immunomodulator, is clinically effective in CLL and can enhance the anti‐CLL effects of CD20 targeting monoclonal antibody, rituximab. Here, we investigated the mechanism of immune‐directed killing of lenalidomide in CLL and evaluated if concurrent targeting of CD20 and BCL2 can enhance this effect. In vitro treatment with lenalidomide enhanced the antibody‐mediated cellular cytotoxicity (ADCC) directed by rituximab in autologous leukaemic cells. Furthermore, peripheral blood monon... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5506071 Fri, 16 Dec 2011 10:18:32 +0100 5506071 http://www.medworm.com/index.php?rid=5506077&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08944.x SummaryThe clinical significance of mixed chimerism following allogeneic haematopoietic stem cell transplantation (HSCT) remains controversial. Its relevance and incidence are probably influenced by the conditioning regimen and incorporation of T‐cell depletion. The presence of recipient chimerism levels >40–50% following T‐cell replete reduced intensity transplantation correlates with a high risk of graft rejection, regardless of donor‐lymphocyte infusions, but it is unclear whether this finding translates to T‐cell depleted transplants. We conducted a retrospective single‐institution analysis of patients receiving alemtuzumab‐based HSCT. 27/152 (18%) evaluable cases had predominantly recipient T‐cell chimerism at 3 months or beyond. By contrast, coincident chimerism ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5506077 Thu, 15 Dec 2011 05:00:00 +0100 5506077 http://www.medworm.com/index.php?rid=5506076&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08970.x SummarySignal transduction pathways in megakaryocytes, a rare population of bone marrow cells, are poorly understood. We have previously shown that the calcineurin‐dependent transcription factor Nuclear Factor of Activated T cells (NFAT) is expressed in megakaryocytes and is required for the transcription of specific megakaryocytic genes. The biological role of NFAT in megakaryocytes, however, is unknown. Here we show that activation of the calcineurin/NFAT pathway in megakaryocytes forces the cells to go into apoptosis. Calcineurin/NFAT activation in megakaryocytes leads to membrane expression of Fas ligand (FASLG), a pro‐apoptotic member of the tumour necrosis factor superfamily. Expression of FASLG was augmented in cells stably overexpressing NFATC2 and suppressed in cells either pr... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5506076 Thu, 15 Dec 2011 05:00:00 +0100 5506076 http://www.medworm.com/index.php?rid=5506075&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08973.x In conclusion, in acute paediatric ITP, enhanced platelet apoptosis is seen at diagnosis that normalizes after IVIg treatment. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5506075 Thu, 15 Dec 2011 05:00:00 +0100 5506075 http://www.medworm.com/index.php?rid=5506074&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08974.x SummaryApproximately 70% of chronic lymphocytic leukaemia (CLL) patients present with early stage disease, therefore defining which patients will progress and require treatment is a major clinical challenge. Here, we present the largest study of prognostic markers ever carried out in Binet stage A patients (n = 1154) with a median follow‐up of 8 years. We assessed the prognostic impact of lymphocyte doubling time (LDT), immunoglobulin gene (IGHV) mutation status, CD38 expression, ZAP‐70 expression and fluorescence in situ hybridization (FISH) cytogenetics with regards to time to first treatment (TTFT) and overall survival (OS). Univariate analysis revealed LDT as the most prognostic parameter for TTFT, with IGHV mutation status most prognostic for OS. CD38 expression, ZAP‐70 ex... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5506074 Thu, 15 Dec 2011 05:00:00 +0100 5506074 http://www.medworm.com/index.php?rid=5506073&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08977.x SummaryThe clinical management of severe pain associated with sickle cell disease (SCD) remains challenging. Development of an optimal therapy would be facilitated by use of murine model(s) with varying degrees of sickling and pain tests that are most sensitive to vaso‐occlusion. We found that young (≤3 months old) NY1DD and S+SAntilles mice (having modest and moderate sickle phenotype, respectively) exhibited evidence of deep tissue/musculoskeletal pain. Deep tissue pain and cold sensitivity in S+SAntilles mice increased significantly with both age and incitement of hypoxia/reoxygenation (H/R). C57/BL6 mice (genetic background strain of NY1DD and S+SAntilles) were hypersensitive to mechanical and heat stimuli, even without the sickle transgene. H/R treatment of HbSS‐BERK mice with... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5506073 Thu, 15 Dec 2011 05:00:00 +0100 5506073 http://www.medworm.com/index.php?rid=5506072&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08981.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5506072 Thu, 15 Dec 2011 05:00:00 +0100 5506072 http://www.medworm.com/index.php?rid=5495470&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08960.x SummaryHeat shock proteins (HSPs) are molecular chaperones that assist proteins in their folding to native structures. HSPs are regarded as possible therapeutic targets in acute myeloid leukaemia (AML). We used bioinformatical approaches to characterize the HSP profile in AML cells from 75 consecutive patients, in addition to the effect of the HSP90 inhibitor 17‐DMAG. Patients harbouring a FLT3‐internal tandem duplication (FLT3‐ITD) were extensively overrepresented in the cluster with high HSP levels, indicating a strong dependence of HSPs in stabilizing FLT3‐ITD encoded oncoproteins. FLT3 ligation further increased the levels of HSP90 and its co‐chaperone HSP70. HSP90 inhibition had a stronger pro‐apoptotic effect for AML cells with FLT3‐ITD than for cells with wild‐type F... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5495470 Tue, 13 Dec 2011 10:37:24 +0100 5495470 http://www.medworm.com/index.php?rid=5487852&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08965.x SummaryLow‐dose alemtuzumab has shown a favourable toxicity profile coupled with good results in terms of efficacy in relapsed/refractory chronic lymphocytic leukaemia (CLL). We conducted a multicentre retrospective study on the routine clinical use of low‐dose alemtuzumab in this patient setting. One hundred and eight relapsed/refractory CLL patients from 11 Italian centres were included in the analysis. All patients had an Eastern Cooperative Oncology Group performance status ≤2 and the majority (84%) had adenopathies <5cm. Low‐dose alemtuzumab was defined as a total weekly dose ≤45 mg and a cumulative dose ≤600 mg given for up to 18 weeks. The overall response rate was 56% (22% complete remissions). After a median follow‐up of 42·2 months, the median overall su... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5487852 Fri, 09 Dec 2011 05:00:00 +0100 5487852 http://www.medworm.com/index.php?rid=5487851&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08978.x This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non‐allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5487851 Fri, 09 Dec 2011 05:00:00 +0100 5487851 http://www.medworm.com/index.php?rid=5487855&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08959.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5487855 Thu, 08 Dec 2011 05:00:00 +0100 5487855 http://www.medworm.com/index.php?rid=5487854&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08962.x SummaryMantle cell lymphoma (MCL) is an aggressive neoplasm with a short survival. Cases with leukaemic MCL and splenomegaly without adenopathies (non‐nodal MCL) may have a more indolent course. To gain insights into the biological features underlying this presentation, we investigated the gene expression profile (GEP) and the IGHV mutational status in a cohort of leukaemic MCL cases. Comparison of MCL with other lymphoproliferative disorders (i.e. splenic marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukaemia) revealed a MCL signature enriched for the following gene categories: mitochondrion, oxidoreductase activity, response to stress, to DNA damage and TP53‐pathway. Furthermore, GEP analysis revealed that non‐nodal MCL cases were characterized by the down‐mod... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5487854 Thu, 08 Dec 2011 05:00:00 +0100 5487854 http://www.medworm.com/index.php?rid=5487853&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08972.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5487853 Thu, 08 Dec 2011 05:00:00 +0100 5487853 http://www.medworm.com/index.php?rid=5477385&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08956.x SummaryKnowledge of the absolute and relative risk of venous thromboembolism (VTE) in and around pregnancy would be crucial in identifying when to commence and cease thromboprophylaxis in women who would benefit from such intervention. We addressed this hypothesis using a large prospective primary care database from the United Kingdom, containing details on 972 683 women aged 15–44 years between 1987 and 2004. Risks of a first VTE during antepartum, postpartum and outside of pregnancy were compared using Poisson regression. The rate of VTE during the third trimester antepartum was six times higher than time outside pregnancy [Incidence Rate Ratio (IRR) = 6·1; 95% confidence interval, 4·7–7·9]. In contrast, both the first (IRR = 1·6) and second (IRR = 2·1) trimester... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477385 Wed, 07 Dec 2011 05:00:00 +0100 5477385 http://www.medworm.com/index.php?rid=5477384&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08958.x This study investigated the clinical activity and toxicity of R‐HCVAD‐AM [rituximab plus HyperCVAD (R‐HCVAD) alternating with high‐dose cytarabine and methotrexate (AM)] in patients with newly diagnosed Mantle Cell Lymphoma (MCL). Patients aged ≤70 years with confirmed MCL received four alternating cycles each of R‐HCVAD and AM. Patients who obtained a partial response proceeded to autologous stem cell transplant. Sixty‐three patients were enrolled and 60 were fully eligible. Median age was 57 years (22–66); 60%, 33% and 7% were classified at low (L)‐, intermediate (I)‐ or high (H)‐risk, respectively, according to the MCL International Prognostic Index (MIPI). Only 22 patients (37%) completed the four cycles and three patients died during therapy. Overall response... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477384 Wed, 07 Dec 2011 05:00:00 +0100 5477384 http://www.medworm.com/index.php?rid=5477383&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08957.x SummaryFor many years, T‐cell acute lymphoblastic leukaemia (T‐ALL) has been considered and treated as a single malignancy, but divergent outcomes in T‐ALL patients receiving uniform treatment protocols encouraged intensive research on the molecular biology of this disease. Recent findings in the field demonstrate that T‐ALL is much more heterogeneous than originally believed and extremely diverse outcomes of patients require refinement of T‐ALL classification, leading to subtype‐specific adjustment of treatment. Many different biological features of T‐ALL blast cells have recently been found to contribute to disease development and patient outcome and their analysis could potentially be introduced into improved diagnostics and classification of the disease. This review focus... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477383 Wed, 07 Dec 2011 05:00:00 +0100 5477383 http://www.medworm.com/index.php?rid=5477382&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08963.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477382 Wed, 07 Dec 2011 05:00:00 +0100 5477382 http://www.medworm.com/index.php?rid=5477381&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08964.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477381 Wed, 07 Dec 2011 05:00:00 +0100 5477381 http://www.medworm.com/index.php?rid=5477380&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08967.x SummaryBirth is the first haemostatic challenge for a child with haemophilia. Our aim was to examine the association between perinatal risk factors and major neonatal bleeding in infants with haemophilia. This observational cohort study in 12 European haemophilia treatment centres (HTC) incorporated 508 children with haemophilia A or B, born between 1990 and 2008. Risk factors for bleeding were analysed by univariate analysis. Head bleeds occurred in 18 (3·5%) children within the first 28 d of life, including three intraparenchymal bleeds, one subdural haematoma and 14 cephalohaematomas. Intra‐cranial bleeds were associated with long‐term neurological sequelae in two (0·4%) cases; no deaths occurred. Assisted delivery (forceps/vacuum) was the only risk factor for neonatal head blee... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477380 Wed, 07 Dec 2011 05:00:00 +0100 5477380 http://www.medworm.com/index.php?rid=5477379&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08968.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477379 Wed, 07 Dec 2011 05:00:00 +0100 5477379 http://www.medworm.com/index.php?rid=5487850&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08966.x SummaryOfatumumab is a new monoclonal antibody (mAb) targeting a novel membrane‐proximal epitope on CD20. To better define ofatumumab’s activity, we conducted pre‐clinical studies in rituximab‐sensitive cell lines (RSCL), rituximab‐resistant cell lines (RRCL), ofatumumab‐exposed cell lines (OECLs), primary lymphoma cells, and a lymphoma xenograft model. RRCL and OECL were generated by repeated exposure of sensitive cells to escalating doses of rituximab or ofatumumab ± human serum. Antibody‐dependent cellular cytotoxicity (ADCC) and complement‐mediated cytotoxicity (CMC) assays were performed to assess cellular sensitivity to rituximab or ofatumumab. Ofatumumab elicited a higher rate of CMC in RSCL, RRCL and primary tumour cells. The chronic exposure of lymphoma cells ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5487850 Thu, 01 Dec 2011 05:00:00 +0100 5487850 http://www.medworm.com/index.php?rid=5477378&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08971.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5477378 Thu, 01 Dec 2011 05:00:00 +0100 5477378 http://www.medworm.com/index.php?rid=5458833&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08955.x SummaryEarly T‐cell precursor acute lymphoblastic leukaemia (ETP‐ALL) is a recently identified subtype of T‐ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT‐ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP‐ALL to a cohort of 91 patients with T‐ALL enrolled in the Tokyo Children’s Cancer Study Group L99‐15 study, which included allogeneic stem cell transplantation (allo‐SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP‐ALL criteria. There were no significant differences in presenting clinical features between th... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5458833 Thu, 01 Dec 2011 05:00:00 +0100 5458833 http://www.medworm.com/index.php?rid=5458834&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08942.x SummaryThe prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population‐based cohort of 505 patients with a median follow‐up time of 10·0 years (range, 4·6–16·0). After excluding 43 patients with concomitant diffuse large B‐cell lymphoma, 345 remained with grade 1–2, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 1–2 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 1–... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5458834 Wed, 30 Nov 2011 05:00:00 +0100 5458834 http://www.medworm.com/index.php?rid=5458836&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08948.x SummaryWhile acute megakaryoblastic leukaemia (AMKL) occurs in children with (DS‐AMKL) and without (paediatric non‐DS‐AMKL) Down syndrome, it can also affect adults without DS (adult non‐DS‐AMKL). We have analysed these subgroups of patients (11 children with DS‐AMKL, 12 children and four adults with non‐DS‐AMKL) for the presence of molecular lesions, including mutations and chromosomal abnormalities studied by sequencing and single nucleotide polymorphism array‐based karyotyping, respectively. In children, AMKL was associated with trisomy 21 (somatic in non‐DS‐AMKL), while numerical aberrations of chromosome 21 were only rarely associated with adult AMKL. DS‐AMKL was also associated with recurrent somatic gains of 1q (4/11 DS‐AMKL patients). In contrast to trisom... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5458836 Mon, 28 Nov 2011 05:00:00 +0100 5458836 http://www.medworm.com/index.php?rid=5458835&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08961.x SummaryMore than 100 different blood and urine biomarkers have been described in sickle cell disease (SCD), with the number increasing rapidly as analytical techniques develop. Nearly all of these biomarkers are abnormal in the steady state, and become more so during complications. The range of abnormalities demonstrates the multisystem nature of SCD and the complex pathophysiology. Some biomarkers indicate damage to specific organs, such as urine albumin:creatinine ratio in nephropathy, whereas others indicate more systemic processes. Biomarkers have been useful in identifying various interrelated pathological mechanisms, including haemolysis, inflammation, hypercoagulability, oxidative stress, reperfusion injury, vasculopathy and endothelial dysfunction. However, most biomarkers correlat... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5458835 Mon, 28 Nov 2011 05:00:00 +0100 5458835 http://www.medworm.com/index.php?rid=5442105&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08953.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5442105 Fri, 25 Nov 2011 10:16:38 +0100 5442105 http://www.medworm.com/index.php?rid=5442107&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08946.x SummaryChanges in DNA copy number (CN) and DNA methylation represent important aberrations for lymphomas and other cancers. Here, for the first time, we show that the Illumina Infinium Methylation (IIM) assay, although not originally designed for CN profiling, is able to estimate CN changes. We compared the IIM CN profiles to those obtained with a standard technique in a series of diffuse large B‐cell lymphomas: the profiles showed a high degree of consensus. The demonstration of CN profiling as an additional function of the IIM assay may impact the choice of platform for methylation profiling of haematological and solid tumours. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5442107 Fri, 25 Nov 2011 05:00:00 +0100 5442107 http://www.medworm.com/index.php?rid=5442106&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08952.x SummaryFrequent blood donors become iron deficient. HFE mutations are present in over 30% of donors. A 24‐month study of 888 first time/reactivated donors and 1537 frequent donors measured haemoglobin and iron status to assess how HFE mutations impact the development of iron deficiency erythropoiesis. Donors with two HFE mutations had increased baseline haemoglobin and iron stores as did those with one mutation, albeit to a lesser extent. Over multiple donations haemoglobin and iron status of donors with HFE mutations paralleled those lacking mutations. The prevalence of HFE mutations was not increased in higher intensity donors. Thus, in general, HFE mutations do not temper donation‐induced changes in haemoglobin and iron status. However, in Black donors there was an increase of H63D ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5442106 Fri, 25 Nov 2011 05:00:00 +0100 5442106 http://www.medworm.com/index.php?rid=5442109&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08950.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5442109 Thu, 24 Nov 2011 05:00:00 +0100 5442109 http://www.medworm.com/index.php?rid=5442108&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08931.x SummaryThe British Committee for Standards in Haematology first produced guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant in 2000. This revision updates those guidelines and covers the areas of diagnosis, treatment and assessment of response to therapy. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5442108 Thu, 24 Nov 2011 05:00:00 +0100 5442108 http://www.medworm.com/index.php?rid=5442111&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08949.x In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4 years. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5442111 Wed, 23 Nov 2011 05:00:00 +0100 5442111 http://www.medworm.com/index.php?rid=5442110&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08951.x This study investigated the expression and activity of FOXO3 in MCL cell lines and in primary cultures. We analysed the expression of key FOXO regulators and targets, and studied the effect of modulators of FOXO function on cell viability and apoptosis. FOXO3 was constitutively inactivated in MCL cell lines, and showed cytoplasmic localization in patient‐derived cells. PI3K and AKT, but not mammalian target of rapamycin (mTOR), inhibitors induced FOXO3 nuclear translocation and activation in correlation with their impact on MCL proliferation and survival. Moreover, FOXO3‐defective cells were resistant to PI3K/AKT inhibitors. Reactivation of FOXO function with a nuclear export inhibitor had a profound effect on cell viability, consistent with FOXO3 nuclear accumulation. Interestingly, i... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5442110 Wed, 23 Nov 2011 05:00:00 +0100 5442110 http://www.medworm.com/index.php?rid=5432430&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08830.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5432430 Tue, 22 Nov 2011 10:16:37 +0100 5432430 http://www.medworm.com/index.php?rid=5432434&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08941.x In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34+ haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in‐house anti‐CD48 mAb induced mild antibody‐dependent cell‐mediated cytotoxicity and marked complement‐dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti‐CD48 mAb significantly inhibited tumour growth in severe combin... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5432434 Mon, 21 Nov 2011 05:00:00 +0100 5432434 http://www.medworm.com/index.php?rid=5432433&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08943.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5432433 Mon, 21 Nov 2011 05:00:00 +0100 5432433 http://www.medworm.com/index.php?rid=5432432&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08945.x SummaryBleeding risk is not predictable in patients with factor XI (FXI; F11) deficiency. In this prospective study, our objectives were to determine the biological determinants for bleeding risk in patients with heterozygous FXI deficiency. Patients were classified as either bleeding patients or non‐bleeding patients by calculating the bleeding score (BS) described for von Willebrand disease. Primary haemostasis, thrombin generation, thromboelastometry, procoagulant proteins, inhibitors, fibrinolysis, and F11 gene mutations were compared between bleeding and non‐bleeding patients. Thirty‐nine patients were included. BS significantly correlated with clinical assessment (P = 0·001), and a score over 3 discriminated between bleeding (n = 15) and non‐bleeding (n = 24) pat... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5432432 Mon, 21 Nov 2011 05:00:00 +0100 5432432 http://www.medworm.com/index.php?rid=5432431&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08947.x SummarySpecific trials on adult Burkitt lymphoma (BL) and ‘unclassifiable’ lymphomas with features intermediate between BL and diffuse large B‐cell lymphoma (BL/DLBCL) are advocated which include substantial numbers of older patients, to improve treatment feasibility, while countering risks of systemic and central nervous system (CNS) recurrences. We prospectively evaluated a modified CODOX‐M/IVAC (CODOX‐M: cyclophosphamide, vincristine, doxorubicin, high‐dose methotrexate; IVAC: ifosfamide, etoposide and high‐dose cytarabine) regimen by the addition of rituximab (R) and liposome‐encapsulated cytarabine (D) to increase antitumour activity and halve the number of intrathecal treatments. Thirty adults (40% >60 years) with BL (n = 15) and BL/DLBCL (n = 15) were ac... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5432431 Mon, 21 Nov 2011 05:00:00 +0100 5432431 http://www.medworm.com/index.php?rid=5423123&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08954.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5423123 Sat, 19 Nov 2011 10:35:15 +0100 5423123 http://www.medworm.com/index.php?rid=5409569&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08938.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5409569 Thu, 17 Nov 2011 01:18:17 +0100 5409569 http://www.medworm.com/index.php?rid=5409571&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08934.x SummaryData on outcome, prognostic factors, and treatment for very elderly non‐Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients ≥80 years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily living (ADLs), and co‐morbidities using the Cumulative Illness Rating Scale‐Geriatrics (CIRS‐G). We identified 303 patients: 170 aggressive NHL (84% B cell/16% T cell) and 133 indolent NHL (82% B cell/18% T cell). Median age was 84 years (80–95). A geriatric syndrome was present in 26% of patients, 18% had ≥1 grade 4 CIRS‐G, and 14% had loss of ADLs. At 49‐month median follow‐up, 4‐year progression‐free (PFS) and overall survival (OS) for agg... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5409571 Wed, 16 Nov 2011 05:00:00 +0100 5409571 http://www.medworm.com/index.php?rid=5409570&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08936.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5409570 Wed, 16 Nov 2011 05:00:00 +0100 5409570 http://www.medworm.com/index.php?rid=5409575&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08935.x SummaryReduced overall fibrinolytic capacity increases the risk of myocardial infarction (MI), as demonstrated in studies with predominantly male participants. We determined the influence of altered fibrinolysis on the risk of MI and ischaemic stroke (IS) in young women. The RATIO (Risk of Arterial Thrombosis In relation to Oral contraceptives) study is a population‐based case‐control study including young women with MI (n = 203), IS (N = 175) and 638 matched healthy controls. Fibrinolytic potential was determined with a tissue factor/tissue plasminogen activator induced clot‐lysis assay. Odds ratios (OR) adjusted for cardiovascular risk factors were obtained with logistic regression. Clot‐lysis time (CLT) was divided into tertiles based on the control group (T1–T3), with... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5409575 Tue, 15 Nov 2011 05:00:00 +0100 5409575 http://www.medworm.com/index.php?rid=5409574&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08937.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5409574 Tue, 15 Nov 2011 05:00:00 +0100 5409574 http://www.medworm.com/index.php?rid=5409573&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08940.x This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower‐dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20 mg/m2 on days 1–5 and temsirolimus 25 mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease‐free survival was 3·5 months, and median overall survival was 4 months (9·1 months for responders). The most common non‐haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30‐d all‐cause induction mortality was... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5409573 Tue, 15 Nov 2011 05:00:00 +0100 5409573 http://www.medworm.com/index.php?rid=5409576&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08923.x SummaryIn a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin‐like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft‐versus‐host disease (GvHD) [hazard risk (HR) 4·2, 95% confidence interval (CI) 1·7–10·1, P = 0·002] and transplantation‐related mortality (HR 4·7, 95% CI 1·6–14·2, P = 0·01). The risk of GvHD furthermore increased when recipients heterozygous for HLA‐C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6·1, 95% CI 1·9–19·2, P = 0·002). We also found that the risk of rejection was highest when the recipient was homo... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5409576 Mon, 14 Nov 2011 05:00:00 +0100 5409576 http://www.medworm.com/index.php?rid=5401340&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08933.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5401340 Sun, 13 Nov 2011 10:08:30 +0100 5401340 http://www.medworm.com/index.php?rid=5401337&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08939.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5401337 Sun, 13 Nov 2011 10:06:12 +0100 5401337 http://www.medworm.com/index.php?rid=5401339&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08928.x SummaryLymphomas can arise within the central nervous system (CNS) as primary CNS lymphoma (PCNSL) typically involving the brain and less often the leptomeninges, eyes, and spinal cord. In contrast to PCNSL, secondary CNS lymphoma (SCNSL) is considered to originate as quasi metastasis from systemic lymphoma spreading to the CNS. Both types of CNS lymphomas are predominantly tumours of the diffuse large B‐cell type and represent aggressive diseases necessitating a rapid diagnosis. Following neuroimaging based on magnetic resonance imaging, stereotaxy and histopathological diagnosis of CNS lymphoma currently remain obligatory to plan treatment. However, progress in cytopathological, immunophenotypic, and molecular genetic analyses of the cerebrospinal fluid (CSF) has been achieved recently... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5401339 Fri, 11 Nov 2011 05:00:00 +0100 5401339 http://www.medworm.com/index.php?rid=5401338&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08932.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5401338 Fri, 11 Nov 2011 05:00:00 +0100 5401338 http://www.medworm.com/index.php?rid=5388765&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08856.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388765 Mon, 07 Nov 2011 05:00:00 +0100 5388765 http://www.medworm.com/index.php?rid=5388764&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08925.x SummaryMonogenic hereditary diseases, such as haemophilia A and B, are ideal targets for gene therapeutic approaches. While these diseases can be treated with protein therapeutics, such as factor VIII (FVIII) or IX (FIX), the notion that permanent transfer of the genes encoding these factors can cure haemophilia is very attractive. An underlying problem with a gene therapy approach, however, is the patient’s immune response to the therapeutic protein (as well as to the transmission vector), leading to the formation of inhibitory antibodies. Even more daunting is reversing an existing immune response in patients with pre‐existing inhibitors. In this review, we will describe the laboratory and clinical progress, and the challenges met thus far, in achieving the goal of gene therapy effic... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388764 Mon, 07 Nov 2011 05:00:00 +0100 5388764 http://www.medworm.com/index.php?rid=5388763&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08929.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388763 Mon, 07 Nov 2011 05:00:00 +0100 5388763 http://www.medworm.com/index.php?rid=5388769&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08924.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388769 Sat, 05 Nov 2011 04:00:00 +0100 5388769 http://www.medworm.com/index.php?rid=5388768&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08921.x SummaryGuidelines on hereditary spherocytosis (HS) published in 2004 (Bolton‐Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical management, (particularly the indications for concomitant splenectomy with cholecystectomy in children with mild HS, and concomitant cholecystectomy with splenectomy in those with asymptomatic gallstones). Further potential long term hazards of splenectomy are now recognised. Advances have been made in our understanding of the biochemistry of the red cell membrane which underpins the choice of tests. Biochemical assays of membranes proteins and genetic analysis may be indicated (rarely) to diagnose atypical cases. The diagnostic value of the eosin‐5‐maleimide (EMA) binding test has been validated in a number of studies... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388768 Sat, 05 Nov 2011 04:00:00 +0100 5388768 http://www.medworm.com/index.php?rid=5388767&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08926.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388767 Sat, 05 Nov 2011 04:00:00 +0100 5388767 http://www.medworm.com/index.php?rid=5388766&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08927.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388766 Sat, 05 Nov 2011 04:00:00 +0100 5388766 http://www.medworm.com/index.php?rid=5388780&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08902.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388780 Thu, 03 Nov 2011 04:00:00 +0100 5388780 http://www.medworm.com/index.php?rid=5388779&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08905.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388779 Thu, 03 Nov 2011 04:00:00 +0100 5388779 http://www.medworm.com/index.php?rid=5388778&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08906.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388778 Thu, 03 Nov 2011 04:00:00 +0100 5388778 http://www.medworm.com/index.php?rid=5388777&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08908.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388777 Thu, 03 Nov 2011 04:00:00 +0100 5388777 http://www.medworm.com/index.php?rid=5388776&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08910.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388776 Thu, 03 Nov 2011 04:00:00 +0100 5388776 http://www.medworm.com/index.php?rid=5388775&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08912.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388775 Thu, 03 Nov 2011 04:00:00 +0100 5388775 http://www.medworm.com/index.php?rid=5388774&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08917.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388774 Thu, 03 Nov 2011 04:00:00 +0100 5388774 http://www.medworm.com/index.php?rid=5388773&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08918.x SummaryThe PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse‐transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34+ cells using TaqMan real‐time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388773 Thu, 03 Nov 2011 04:00:00 +0100 5388773 http://www.medworm.com/index.php?rid=5388772&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08919.x SummaryHaemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including haemarthroses, leading to orthopaedic complications. The pathogenesis of haemophilic joint arthropathy continues to be explored and there is evidence to suggest that iron, cytokines, and neo angiogenesis can initiate synovial and early cartilage damage resulting in molecular changes and the perpetuation of a chronic inflammatory state. This joint arthropathy has long term consequences for bone health resulting in chronic pain and quality of life issues in the individual with haemophilia. Haemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis). However, high costs and the need for venous access devices in younger children con... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388772 Thu, 03 Nov 2011 04:00:00 +0100 5388772 http://www.medworm.com/index.php?rid=5388771&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08920.x SummaryDeveloped countries, such as the United Kingdom, are experiencing a change in demographics resulting in the largest proportion of adults over 65 years of age that our health systems have ever experienced. As such, haematologists must be prepared to evaluate and treat anaemia in a more complicated patient population, but sufficient evidence‐based guidelines are lacking. Critical next steps that must be taken to ensure the best care of this population include the determination of appropriate haemoglobin concentrations for older adults in light of age, gender, race, and comorbidities; the development of interventional trials that address physical performance outcomes in addition to haemoglobin targets; and translational studies which address the molecular pathogenesis of anaemia in... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388771 Thu, 03 Nov 2011 04:00:00 +0100 5388771 http://www.medworm.com/index.php?rid=5388770&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08922.x SummaryCoagulopathy occurs in most patients with (APML) and is life‐threatening; therefore prompt diagnosis and recognition of any coagulation defect is imperative. Unfortunately haemorrhage remains a major cause of early death, preventing some from reaching treatment. The coagulopathy is caused directly or indirectly by the leukaemic cells through expression of activators of coagulation and fibrinolysis, proteases and cytokine generation, compounded by failure of platelet production due to marrow invasion. At presentation the predominant feature is usually hyperfibrinolysis. Since the introduction of all‐trans retinoic acid (ATRA), patient outcome has dramatically improved; yet, haemorrhagic complications remain the most frequent cause of mortality. Thrombotic complications occur but ... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388770 Thu, 03 Nov 2011 04:00:00 +0100 5388770 http://www.medworm.com/index.php?rid=5388762&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08930.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5388762 Tue, 01 Nov 2011 04:00:00 +0100 5388762 http://www.medworm.com/index.php?rid=5348978&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08916.x SummaryCompound heterozygotes for sickle haemoglobin (HbS) and hereditary persistence of fetal haemoglobin (HPFH) have high fetal haemoglobin (HbF) levels but few, if any, sickle cell disease‐related complications. We studied 30 cases of HbS‐HPFH (types 1 and 2), confirmed by molecular analysis, and report the haematological features and change in HbF levels over time. These results were compared to those of patients with sickle cell anaemia or HbS‐β0 thalassaemia, including a subgroup of patients carrying the XmnI polymorphism, known to be associated with elevated HbF. Among the HbS‐HPFH patients, HbF level was 50–90% during infancy and declined steeply within the first few years of life, stabilizing between ages 3 and 5 years, at approximately 30%. Mean HbF of individuals ag... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5348978 Wed, 26 Oct 2011 21:34:44 +0100 5348978 http://www.medworm.com/index.php?rid=5348983&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08907.x SummaryRichter transformation in chronic lymphocytic leukaemia (CLL) represents an entity of considerable genetic, molecular, immunological and clinical heterogeneity. A rare occurrence, Hodgkin variant of Richter syndrome, has not been comprehensively characterized or systematized to date. We conducted a retrospective analysis of the existing cases of Hodgkin lymphoma as Richter syndrome reported in the medical literature in the previous three and a half decades. Our search identified 86 such patients; this entity affects predominantly older men and the most common histological subtype is mixed cellularity. Interval between the diagnosis of CLL and subsequent development of Hodgkin lymphoma is circa 4·3 years. The overall survival of patients was approximately 1·7 years in our analy... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5348983 Mon, 24 Oct 2011 04:00:00 +0100 5348983 http://www.medworm.com/index.php?rid=5348982&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08911.x SummaryTET2 mutations have been identified in 10–25% of patients with myeloid malignancies, but TET2 gene copy number alterations remain to be evaluated. We performed interphase and metaphase fluorescence in situ hybridization (FISH), using newly designed probes that span TET2, in 893 patients with acute myeloid leukaemia (AML) and chronic myeloid malignancies and validated the new assay by single nucleotide polymorphism arrays. Next‐generation sequencing for molecular TET2 mutations was performed in 37/50 del(TET2) patients. We identified TET2 deletions in 50/893 patients (26 males, 24 females; 44–87 years) resulting in a 5·6% frequency [22/425 AML (5·2%), 15/217 chronic myelomonocytic leukaemia (CMML; 6·9%), 9/188 myelodysplastic syndromes (4·8%), 4/63 myeloproliferative neop... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5348982 Mon, 24 Oct 2011 04:00:00 +0100 5348982 http://www.medworm.com/index.php?rid=5348981&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08913.x SummaryThe long‐term antibody responses to re‐immunization in recipients of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) have not been well studied. We prospectively and longitudinally evaluated the antibody responses to eight vaccine antigens (diphtheria, tetanus, pertussis, measles, mumps, rubella, hepatitis B, and poliovirus) and assessed the factors associated with negative titres in 210 allo‐HSCT recipients at St. Jude Children’s Research Hospital. Antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95·7%), rubella (92·3%), poliovirus (97·9%), and, in diphtheria‐tetanus‐acellular pertussis (DTaP) recipients, diphtheria (100%). However, responses to pertussis (25·0%), measles (66·7%), mu... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5348981 Mon, 24 Oct 2011 04:00:00 +0100 5348981 http://www.medworm.com/index.php?rid=5348980&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08914.x SummaryPatients with paroxysmal nocturnal haemoglobinuria (PNH) have expanded clonal cells bearing a somatic mutation in the PIGA gene. Our previous study on two PNH patients with chromosome 12 rearrangements demonstrated the involvement of HMGA2 expression in clonal expansion. The present study investigated HMGA2 expression in PNH patients without chromosomal abnormalities. The expression of short HMGA2 with latent exon was significantly high in peripheral blood cells from 18 of 24 patients. Over‐expression of truncated HMGA2 in mouse bone marrow cells caused expansion in recipient mice. These results support the idea that deregulated expression of HMGA2 causes expansion of PNH cells. (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5348980 Mon, 24 Oct 2011 04:00:00 +0100 5348980 http://www.medworm.com/index.php?rid=5348979&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08915.x SummaryLangerhans cell histiocytosis (LCH) is a proliferative disease of cells that share phenotypic characteristics with the primary antigen presenting cells of the epidermis. Its clinical manifestations are highly variable, extending from very benign forms to a disseminated, aggressive disease that causes significant mortality. Although many of the fundamental pathogenetic features of LCH have been enigmatic, recent advances have led to a much clearer understanding of the disease. In particular, careful molecular analyses of mouse models and human LCH samples suggest that LCH’s cell of origin may not be the epidermal LC itself but a myeloid‐derived precursor. Advanced genomic technologies have revealed the presence of activating, somatic BRAF mutations in the majority of patient spec... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5348979 Mon, 24 Oct 2011 04:00:00 +0100 5348979 http://www.medworm.com/index.php?rid=5337198&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08901.x SummaryGene expression profiling (GEP) of primary leukaemic cells (PLC) from 157 paediatric B‐lineage acute lymphoblastic leukaemia (ALL) patients, including a direct comparison of matched pair initial diagnosis versus first relapse leukaemic specimens, provided previously unknown evidence that relapse clones are characterized by significantly higher expression levels of a CD22 exon 12 deletion (CD22ΔE12)‐associated signature transcriptome than the PLC from newly diagnosed patients. In agreement with and validating these GEP results, reverse transcription polymerase chain reaction and Western blot analysis of PLC from 19 of 19 paediatric ALL patients in first bone marrow relapse occurring within 12 months of the completion of primary therapy confirmed them to be CD22ΔE12+. Likewise... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5337198 Sat, 22 Oct 2011 23:08:12 +0100 5337198 http://www.medworm.com/index.php?rid=5337199&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08885.x SummaryThe severely injured trauma patient often arrives in the emergency department bleeding, coagulopathic and in need of a blood transfusion. The diagnosis and management of these patients has vastly improved with a better understanding of acute traumatic coagulopathy (ATC). In the emergency setting, traditional laboratory coagulation screens are of limited use in the diagnosis and management of life‐threatening bleeding. Whole blood assays, such as thrombelastography (TEG) and rotational thrombelastometry (ROTEM) provide a rapid evaluation of clot formation, strength and lysis. Rapid diagnosis of ATC and aggressive haemostatic transfusion strategies utilizing early high doses of plasma are associated with improved outcomes in trauma. At present there is no accurate guide for transfus... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5337199 Fri, 21 Oct 2011 04:00:00 +0100 5337199 http://www.medworm.com/index.php?rid=5337200&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08882.x SummaryLenalidomide has demonstrated impressive antileukaemic effects in patients with chronic lymphocytic leukaemia (CLL). The mechanism(s) by which it mediates these effects remain unclear. Clinically, CLL patients treated with lenalidomide demonstrate an acute inflammatory reaction, the tumour flare reaction that is suggestive of an immune activation phenomenon. Samples from CLL patients treated with lenalidomide were used to evaluate its effect on the tumour cell and components of its microenvironment (immune cellular and cytokine). Lenalidomide was unable to directly induce apoptosis in CLL cells in vitro, however it modulated costimulatory (CD80, CD83, CD86) surface molecules on CLL cells in vitro and in vivo. Concurrently, we demonstrated that NK cell proliferation was induced by le... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5337200 Thu, 20 Oct 2011 04:00:00 +0100 5337200 http://www.medworm.com/index.php?rid=5337201&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2010.08468.x SummaryAdenovirus infection is a significant complication in paediatric AlloSCT recipients with a mortality rate for disseminated adenovirus that may exceed 80%. We sought to determine the incidence, risk factors, and associated outcomes of adenovirus infection in 123 consecutive paediatric AlloSCT recipients. Adenovirus was diagnosed by antigen detection or viral culture, and was defined by isolation of virus with presence of correlating clinical symptoms. The probability of developing adenovirus infection was 12·3% (CI95 6·0–18·6). There were no statistically significant differences in probability of adenovirus infection in univariate analysis of risk factors including donor source, use of ATG/Alemtuzumab, ≥Grade II GVHD, among others (age, diagnosis, conditioning regimen). Probab... British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5337201 Tue, 18 Oct 2011 04:00:00 +0100 5337201 http://www.medworm.com/index.php?rid=5316307&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08891.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5316307 Sat, 15 Oct 2011 12:10:18 +0100 5316307 http://www.medworm.com/index.php?rid=5305167&cid=s_29464_19_f&fid=29464&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1365-2141.2011.08909.x (Source: British Journal of Haematology) British Journal of Haematology journals http://www.medworm.com/rss/comments.php?id=5305167 Wed, 12 Oct 2011 09:31:48 +0100 5305167