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 'Seminars in Hematology' source. Wed, 08 Feb 2012 17:42:11 +0100 http://www.medworm.com/index.php?rid=5561339&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001144%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561339 Sun, 01 Jan 2012 05:00:00 +0100 5561339 http://www.medworm.com/index.php?rid=5561338&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001132%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561338 Sun, 01 Jan 2012 05:00:00 +0100 5561338 http://www.medworm.com/index.php?rid=5561337&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001120%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561337 Sun, 01 Jan 2012 05:00:00 +0100 5561337 http://www.medworm.com/index.php?rid=5561336&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001119%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561336 Sun, 01 Jan 2012 05:00:00 +0100 5561336 http://www.medworm.com/index.php?rid=5561335&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000989%2Fabstract%3Frss%3Dyes Over the last two decades quality of life (QoL) and the social challenges of allogeneic hematopoietic stem cell transplant (allo-HSCT) survivors have been emerging as subjects of extensive research and are now considered as very important aspects in the pretransplant evaluation and management of allo-HSCT recipients. Recognition of QoL challenges in allo-HSCT survivors allows timely interventions leading to improvement of post-transplant outcomes. It needs to be recognized that long-lasting life changes associated with survivorship after allo-HSCT also significantly affect QoL of partners of allo-HSCT survivors. Currently, resources should be focused on how research findings can be used by patients, their partners, and physicians to optimize QoL and psychosocial adjustment. (Source: Semina... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561335 Sun, 01 Jan 2012 05:00:00 +0100 5561335 http://www.medworm.com/index.php?rid=5561334&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001065%2Fabstract%3Frss%3Dyes Over the past 50 years there has been considerable progress and success in the field of allogeneic hematopoietic stem cell transplant (HSCT) in children. In addition there has been significant improvement in transplant outcomes for both malignant and nonmalignant indications. These improved outcomes have resulted in many long-term survivors who are experiencing substantial long-term morbidities. There are limited data examining the long-term complications of transplant on the various organs. This issue is complicated by the fact that children receive their transplant at different stages of their growth and development (ie, infant, toddler, child, adolescent, and young adult). Each of these developmental stages has different sensitivities to treatment and can result in different sets of com... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561334 Sun, 01 Jan 2012 05:00:00 +0100 5561334 http://www.medworm.com/index.php?rid=5561333&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000965%2Fabstract%3Frss%3Dyes Female long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) incur a significant burden of late effects. Genital graft-versus-host disease (GVHD), human papillomavirus (HPV) reactivation, ovarian failure and infertility, sexual dysfunction, and osteoporosis are concerns that can significantly impact quality of life. This review examines the risk, pathogenesis, clinical presentation, and implications of these common complications. Recommendations are provided for evaluation and management of these late effects and other obstetric and gynecologic issues that may arise in this patient population. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561333 Sun, 01 Jan 2012 05:00:00 +0100 5561333 http://www.medworm.com/index.php?rid=5561332&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001028%2Fabstract%3Frss%3Dyes Chronic kidney disease (CKD) occurs commonly (prevalence of approximately 20% in a large series) after allogeneic hematopoietic stem cell transplantation (HSCT). There are three distinct clinical entities that occur after HSCT: thrombotic microangiopathy (TMA), nephrotic syndrome (NS), and idiopathic or graft-versus-host disease (GVHD)-related CKD. Acute renal function decline occurs in the majority of patients in the first months after transplantation. This acute kidney injury can persist and is a risk factor for the later development of CKD. However, the potentially independent role of GVHD, chronic inflammation, and chronic exposure to calcineurin inhibitors in the development and progression of CKD warrants further investigation. Careful monitoring of blood pressure, renal function, an... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561332 Sun, 01 Jan 2012 05:00:00 +0100 5561332 http://www.medworm.com/index.php?rid=5561331&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001041%2Fabstract%3Frss%3Dyes As survival rates continue to increase after allogeneic stem cell transplant (allo-SCT), the associated long-term complications of transplant need to be taken into consideration. Here, we review the endocrine and metabolic complications associated with transplant survivors, including diabetes, dyslipidemia, hypertension, cardiovascular disease, hypogonadism, vitamin D deficiency, osteoporosis, thyroid disease, adrenal dysfunction, and pituitary disorders, and provide a brief summary of evaluation and treatment of these conditions. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561331 Sun, 01 Jan 2012 05:00:00 +0100 5561331 http://www.medworm.com/index.php?rid=5561330&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001016%2Fabstract%3Frss%3Dyes Advances in transplantation technology and supportive care measures have resulted in significant decrease in early mortality resulting in continued growth in the number of long-term hematopoietic cell transplantation (HCT) survivors. The intensity of chemotherapy and total body irradiation regimen used pretransplantation to eradicate the primary disease can lead to organ toxicities, including significant bone complications after HCT. Bone loss is frequent in HCT recipients and results from impaired bone mineralization through disturbances of calcium and vitamin D homeostasis, osteoblast and osteoclast dysfunction, and deficiencies in growth or gonadal hormone secretion. Exposure to glucocorticoids and calcineurin inhibitors for prevention and treatment of graft-versus-host disease (GVHD) r... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561330 Sun, 01 Jan 2012 05:00:00 +0100 5561330 http://www.medworm.com/index.php?rid=5561329&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001004%2Fabstract%3Frss%3Dyes Gastrointestinal and hepatobiliary problems in the second year after allogeneic hematopoietic cell transplant (HCT) are usually a continuation of symptoms of protracted acute graft-versus-host disease (GVHD), chronic GVHD, medication side effects, and infection related to immune suppression. As time passes, as tolerance develops, and as immunity improves, the frequency and severity of these problems wane, but new problems involving the gut and liver may arise, sometimes insidiously and sometimes decades after the transplant. Examples are esophageal strictures related to chronic GVHD, gallstones, cirrhosis caused by chronic hepatitis C, secondary malignancy, and rare cases of pancreatic atrophy. One very common complication of transplantation, iron overload, is often associated with substan... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561329 Sun, 01 Jan 2012 05:00:00 +0100 5561329 http://www.medworm.com/index.php?rid=5561328&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000977%2Fabstract%3Frss%3Dyes Management of high serum ferritin levels after allogeneic hematopoietic stem cell transplantation (allo-HSCT) should, from the diagnostic standpoint, be based on the pathophysiological mechanisms underlying the development of hyperferritinemia. This knowledge is essential for differentiating increased serum ferritin due to iron overload from “non–iron overload” situations such as inflammation, metabolic syndrome, or hepatitis. Once body iron overload has been proven, especially by quantifying tissue iron excess with the noninvasive magnetic resonance imaging (MRI) method, it is important, considering the damaging effects of chronic iron overload in these patients, to start iron depletive therapy by oral chelation or phlebotomy. At present, more data are needed to assess the long-term... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561328 Sun, 01 Jan 2012 05:00:00 +0100 5561328 http://www.medworm.com/index.php?rid=5561327&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000953%2Fabstract%3Frss%3Dyes Cardiovascular diseases (CVD) are emerging late effects after allogeneic hematopoietic stem cell transplantation (allo-HSCT), leading to considerable morbidity and mortality. These late CVD are in most cases related to enhanced atherosclerosis, promoted by the early appearance after transplantation of cardiovascular risk factors. According to the data obtained from the general population it is very likely that early intervention on these cardiovascular risk factors might defer the appearance of late CVD. This review focuses on the published data of cardiovascular diseases after transplantation, the potential associated risk factors, and the postulated pathophysiological mechanisms. A suggested approach for early identification of patients at risk, optimal surveillance, and screening of the... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561327 Sun, 01 Jan 2012 05:00:00 +0100 5561327 http://www.medworm.com/index.php?rid=5561326&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000990%2Fabstract%3Frss%3Dyes Bronchiolitis obliterans syndrome (BOS) is a life-threatening complication that occurs among recipients of allogeneic lung and hematopoietic stem cell transplantation (allo-HSCT). BOS usually occurs within the first 2 years but may develop as late as 5 years after allo-HSCT. Recent prevalence estimates suggest that BOS is likely underdiagnosed in the clinical setting and that 14% of all long-term survivors with chronic graft-versus-host disease (GVHD) may develop BOS. It is difficult to diagnose and once respiratory symptoms appear, most allo-HSCT recipients show severe airflow obstruction. This may be due, at least in part, to the low sensitivity of standard spirometry in detecting small airways obstruction and lack of formal recommendations for screening for this complication. The progno... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561326 Sun, 01 Jan 2012 05:00:00 +0100 5561326 http://www.medworm.com/index.php?rid=5561325&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631100103X%2Fabstract%3Frss%3Dyes Even though the overall outcome after allogeneic transplant has improved significantly in the last decades, late infectious diseases are still the most important causes of late morbidity and mortality. Here, impaired immune reconstitution and therapy of chronic graft-versus-host disease (GVHD) represent the major risk factors. In this review, we give a comprehensive overview of late infectious complications and summarize possible diagnostic and therapeutic interventions to prevent these complications. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561325 Sun, 01 Jan 2012 05:00:00 +0100 5561325 http://www.medworm.com/index.php?rid=5561324&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001077%2Fabstract%3Frss%3Dyes With greater numbers of patients surviving long-term after allogeneic stem cell transplantation (SCT), second malignancies have increasingly been recognized. Secondary solid tumors, the most prevalent second malignancies after allogeneic SCT, are reviewed with particular emphasis on recent developments in the pathogenesis, early diagnosis, and treatment of these transplant-related complications. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561324 Sun, 01 Jan 2012 05:00:00 +0100 5561324 http://www.medworm.com/index.php?rid=5561323&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001089%2Fabstract%3Frss%3Dyes Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides curative therapy for a variety of diseases. Over the past several decades, significant advances have been made in the field of allo-HSCT and now allo-HSCT has become an integral part of treatment modality for a variety of hematologic malignancies and some nonmalignant diseases. The development of less toxic pretransplant conditioning regimens, more effective prophylaxis of graft-versus-host- disease (GVHD), improved infection control, and other advances in transplant technology have resulted in a rapidly growing number of transplant recipients surviving long-term free of the disease for which they were transplanted. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561323 Sun, 01 Jan 2012 05:00:00 +0100 5561323 http://www.medworm.com/index.php?rid=5561322&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311001090%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5561322 Sun, 01 Jan 2012 05:00:00 +0100 5561322 http://www.medworm.com/index.php?rid=5316401&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000850%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316401 Sat, 01 Oct 2011 04:00:00 +0100 5316401 http://www.medworm.com/index.php?rid=5316400&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000849%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316400 Sat, 01 Oct 2011 04:00:00 +0100 5316400 http://www.medworm.com/index.php?rid=5316399&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000837%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316399 Sat, 01 Oct 2011 04:00:00 +0100 5316399 http://www.medworm.com/index.php?rid=5316398&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000722%2Fabstract%3Frss%3Dyes In the article entitled “A Dirty Dozen: Twelve P-Value Misconceptions,” by Steven Goodman (Semin Hematol 45:135–140, 2008), the correct equation for Bayes' theorem on page 139 is: (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316398 Sat, 01 Oct 2011 04:00:00 +0100 5316398 http://www.medworm.com/index.php?rid=5316397&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000783%2Fabstract%3Frss%3Dyes A thorough understanding of the pharmacology, pharmacokinetics, and pharmacodynamics of the most commonly prescribed anticoagulants is necessary to ensure optimal therapeutic outcomes and patient safety. Evidence is available to guide some, but not all aspects of anticoagulation therapy initiation. Issues related to the initiation of anticoagulation therapy, including the resumption of therapy following interruption of anticoagulation for invasive procedures, are reviewed. Initiating unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux is challenging for patients with renal dysfunction and obesity. UFH is preferred in patients with severe renal dysfunction. Morbidly obese patients may require higher than usual prophylactic doses of LMWH. Therapeutic doses of L... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316397 Sat, 01 Oct 2011 04:00:00 +0100 5316397 http://www.medworm.com/index.php?rid=5316396&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000795%2Fabstract%3Frss%3Dyes As new anticoagulants become available, and the number of anticoagulated patients continues to rise, it is necessary to know how to deal with associated bleeding complications. In this review, reversal strategies for traditional anticoagulants (warfarin and heparin) as well as newer anticoagulants are described. Prothrombin complex concentrates (PPCs) can be used to reverse vitamin K antagonists (VKA), and plasma may be used where they are not available. Recombinant activated factor VII (rFVIIa) may be useful to reverse pentasaccharide anticoagulants. 1-Desamino-8-d-arginine vasopressin (DDAVP), cryoprecipitate, PCCs, and dialysis may help to reverse direct thrombin inhibitors, while rFVIIa seems to be ineffective. The effect of direct factor Xa inhibitors may be reversed by PCCs, FVIIa, o... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316396 Sat, 01 Oct 2011 04:00:00 +0100 5316396 http://www.medworm.com/index.php?rid=5316395&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000746%2Fabstract%3Frss%3Dyes This article reviews the available literature and provides guidance for the management and prevention of VTE during pregnancy. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316395 Sat, 01 Oct 2011 04:00:00 +0100 5316395 http://www.medworm.com/index.php?rid=5316394&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631100076X%2Fabstract%3Frss%3Dyes Venous thromboses in unusual sites are rare and heterogenous manifestations of venous thromboembolism (VTE). These uncommon diseases are each characterized by peculiar pathophysiological and clinical features, mainly reflecting the different characteristics of the organs of origin. Moreover, the relative frequency and importance of risk factors associated with their development may be different compared to those of the classical manifestations of VTE, such as deep vein thrombosis of the lower limbs or pulmonary embolism. The need for anticoagulant therapy for unusual site thrombosis (UST) is generally accepted. However, several questions remain unanswered: what is the best therapeutic agent, is it safe, and for how long should it be used? These questions persist mainly due to the low level... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316394 Sat, 01 Oct 2011 04:00:00 +0100 5316394 http://www.medworm.com/index.php?rid=5316393&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000771%2Fabstract%3Frss%3Dyes The association between venous thromboembolism (VTE) and malignancy is well established. Recent interest has focused on standards of care for prophylaxis, diagnosis, and treatment of malignancy-associated thrombosis. Anticoagulant management in cancer patients has unique complexities such as prolonged hospitalization, extensive surgeries, extended periods of inactivity, indwelling central venous catheters (CVC), thrombocytopenia, and pro-thrombotic medications. Here we will explore current recommendations for various specific clinical scenarios for cancer-associated thromboses. We will make evidence-based recommendations wherever possible; however, several of the scenarios here were included because pertinent high-quality evidence does not exist. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316393 Sat, 01 Oct 2011 04:00:00 +0100 5316393 http://www.medworm.com/index.php?rid=5316392&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000734%2Fabstract%3Frss%3Dyes Thrombocytopenia is one of the most common reasons for inpatient hematology consultations. The main challenges in the management of hospitalized patients with thrombocytopenia are to identify the underlying cause and to recognize when urgent interventions are required. Examination of the blood film is essential in the investigation of any patient with thrombocytopenia, and the context in which thrombocytopenia occurred, its severity, timing, and association with bleeding are important clues to the diagnosis. Evidence from randomized trials provides some guidance on the use of platelet transfusions for patients with chemotherapy-induced thrombocytopenia; however, recommendations for non-oncology patients are based largely on expert opinion. Thrombocytopenia does not protect against thrombos... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316392 Sat, 01 Oct 2011 04:00:00 +0100 5316392 http://www.medworm.com/index.php?rid=5316391&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000758%2Fabstract%3Frss%3Dyes While our understanding of the pathophysiology of both congenital and acquired forms of thrombotic thrombocytopenic purpura (TTP) has increased, it is only over the past couple of years that this understanding has been translated into clinically significant advances in the diagnosis, management, and treatment of TTP. More specifically, our understanding of the central role of the ADAMTS13 protease in the pathophysiology of TTP has allowed ADAMTS13 testing to have a more prominent role in confirming or re-evaluating the clinical diagnosis of idiopathic TTP with the finding of severely deficient or measurable ADAMTS13, respectively. Additionally, measurement of ADAMTS13 activity at presentation and during remission may be useful to predict both the risk of exacerbation and relapse in patient... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316391 Sat, 01 Oct 2011 04:00:00 +0100 5316391 http://www.medworm.com/index.php?rid=5316390&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000801%2Fabstract%3Frss%3Dyes Practicing clinicians are frequently faced with clinical problems for which there is little or no clinical guidance. Problems such as how to best initiate anticoagulation, diagnosis and management of thrombocytopenia in hospitalized patients, and “state-of-the-art” management of thrombotic thrombocytopenic purpura are difficult and yet are oftentimes presented to practicing clinicians. In this addition of Seminars in Hematology, we present a series of papers outlining “best evidence” for the management of frequent but relatively poorly studied clinical problems in hematology. Our goal is to provide guidance to practicing clinicians and to spur interest in research in these clinical areas; in many cases such research would be relatively straightforward to perform and would have a hi... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316390 Sat, 01 Oct 2011 04:00:00 +0100 5316390 http://www.medworm.com/index.php?rid=5316389&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000825%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316389 Sat, 01 Oct 2011 04:00:00 +0100 5316389 http://www.medworm.com/index.php?rid=5316388&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000813%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5316388 Sat, 01 Oct 2011 04:00:00 +0100 5316388 http://www.medworm.com/index.php?rid=5053740&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000606%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053740 Thu, 30 Jun 2011 23:00:00 +0100 5053740 http://www.medworm.com/index.php?rid=5053739&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631100059X%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053739 Thu, 30 Jun 2011 23:00:00 +0100 5053739 http://www.medworm.com/index.php?rid=5053738&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000588%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053738 Thu, 30 Jun 2011 23:00:00 +0100 5053738 http://www.medworm.com/index.php?rid=5053737&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000576%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053737 Thu, 30 Jun 2011 23:00:00 +0100 5053737 http://www.medworm.com/index.php?rid=5053736&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000369%2Fabstract%3Frss%3Dyes Despite the use of intensive chemotherapy regimens with or without autologous stem cell transplant (auto-SCT) support, the clinical course of mantle cell lymphoma (MCL) remains characterized by iterative relapses and is still an incurable disease. The impact of allogeneic stem cell transplantation (allo-SCT) in MCL emerged in the late 1990s when it was shown that myeloablative allo-SCT could potentially cure some relapsed/refractory MCL patients. This curative impact is sustained by a graft-versus-disease (GVD-MCL) effect. However, toxicity and mortality following myeloablative allo-SCT are too high and have limited its use for patients aged under 65 years at diagnosis. Reduced-intensity conditioning regimens (RIC-allo) entail lower toxicity and reduced transplant-related mortality (TRM), ... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053736 Thu, 30 Jun 2011 23:00:00 +0100 5053736 http://www.medworm.com/index.php?rid=5053735&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000503%2Fabstract%3Frss%3Dyes Mantle cell lymphoma (MCL) is a malignancy of mature B cells characterized by the translocation t(11;14) that leads to aberrant expression of cyclin D1. Response to first-line chemotherapy is good, but most patients relapse, resulting in a median survival of 5 to 7 years. The important PI3K/AKT/mTOR pathway can be targeted with small molecules. mTOR inhibitors have clinical activity and temsirolimus has been approved in Europe. Second-generation mTOR inhibitors and the PI3K inhibitor CAL-101 offer additional means to target the pathway. Promising results with the BTK inhibitor PCI-32765 suggest that B-cell receptor signaling could play a role. For unknown reasons, MCL appears to be particularly sensitive to disruption of protein homeostasis. The proteasome inhibitor bortezomib achieves res... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053735 Thu, 30 Jun 2011 23:00:00 +0100 5053735 http://www.medworm.com/index.php?rid=5053734&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000357%2Fabstract%3Frss%3Dyes Treatment of elderly patients with a mantle cell lymphoma (MCL) is a challenge. High-dose cytarabine and autologous transplantation, both important components of the treatment in younger patients, are not feasible for most elderly patients. However, in fit elderly patients long progression-free survival and molecular remissions are possible. The regimen most commonly used is rituximab combined with an anthracycline-combination therapy, ie, R-CHOP. An alternative is rituximab combined with a purine analogue-containing regimen, ie, fludarabine with cyclophosphamide (R-FC). The results of a large randomized study comparing these two regimens are expected soon. Maintenance therapy with rituximab after induction improves progression-free survival. Relapse of lymphoma will occur in all patients,... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053734 Thu, 30 Jun 2011 23:00:00 +0100 5053734 http://www.medworm.com/index.php?rid=5053733&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000539%2Fabstract%3Frss%3Dyes Mantle cell lymphoma (MCL) is an individualized entity that is well characterized at the molecular level and considered to be a disease of elderly patients. However, about half of patients are less than 65 years of age and may benefit from intensive therapies. Although MCL has been considered during the last three decades as an incurable disease with current chemotherapy regimens, in young patients recent intense chemo-immunotherapy (CIT) induction regimens including high-dose cytarabine with consolidation with autologous stem cell transplantation (ASCT) have increased significantly the outcome of patients with the disease; some may experience long-term survival free of disease and may even be cured. In addition, new drugs targeting some pathways, including molecular alterations of the dis... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053733 Thu, 30 Jun 2011 23:00:00 +0100 5053733 http://www.medworm.com/index.php?rid=5053732&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000370%2Fabstract%3Frss%3Dyes Up to one third of patients with mantle cell lymphoma (MCL) may be observed for a period of months to years before developing indications for therapy. Importantly, observational studies suggest that this approach has no apparent negative impact on their overall survival. Although there is broad agreement on which patients require early therapy, identification of patients with less aggressive disease can be challenging. Clinical tools such as the Mantle Cell International Prognostic Index (MIPI) and Ki67 are effective at predicting survival but may not always correspond with indications for treatment. Research tools such as the proliferative signature are attractive but have yet to be evaluated in this context. Physicians, therefore, must make decisions regarding therapy based on the best a... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053732 Thu, 30 Jun 2011 23:00:00 +0100 5053732 http://www.medworm.com/index.php?rid=5053731&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000527%2Fabstract%3Frss%3Dyes Mantle cell lymphoma (MCL) has only recently been recognized as a separate biologically defined lymphoma entity. Due to its low incidence, many reports on clinical prognostic factors are limited by small patient numbers. The MCL International Prognostic Index (MIPI) was developed using data of more than 400 patients treated within randomized trials of the European MCL Network. Based on the routinely available clinical prognostic factors age, performance status, lactate dehydrogenase (LDH), and white blood cell count, three MIPI risk groups were defined with different survival. The MIPI has been externally validated by several independent groups. It therefore may be used to report and compare risk profiles of MCL patient groups, to stratify randomization in clinical trials, to perform risk ... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053731 Thu, 30 Jun 2011 23:00:00 +0100 5053731 http://www.medworm.com/index.php?rid=5053730&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000515%2Fabstract%3Frss%3Dyes The prognostic impact of minimal residual disease (MRD) has been demonstrated for several hematologic malignancies. While in acute lymphoblastic leukemias MRD assessment by polymerase chain reaction (PCR)-based methods has been established as an important tool for clinical risk assessment and is part of clinical management, data demonstrating a prognostic value of MRD in mantle cell lymphoma (MCL) were sparse and results from randomized trials have been published only recently. In the present review technical aspects of different MRD detection methods are discussed, as well as the prognostic relevance of MRD in the context of clinical trials in patients with MCL. Furthermore, recommendations are given for workflow and useful implication of MRD in future clinical trials design. (Source: Sem... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053730 Thu, 30 Jun 2011 23:00:00 +0100 5053730 http://www.medworm.com/index.php?rid=5053729&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000345%2Fabstract%3Frss%3Dyes Mantle cell lymphoma (MCL) is characterized by adverse prognosis and the development of novel therapeutic approaches is essential to improve outcome. The introduction of gene expression profiling using DNA microarrays has significantly enhanced our understanding of the molecular pathogenesis of MCL, which is a prerequisite to the development of novel treatment strategies. Gene expression profiling can furthermore be applied to predict treatment response at diagnosis and thus can be used to assess a patient's individual risk profile. This review summarizes our current knowledge on the use of microarray technology in MCL. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053729 Thu, 30 Jun 2011 23:00:00 +0100 5053729 http://www.medworm.com/index.php?rid=5053728&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000461%2Fabstract%3Frss%3Dyes Mantle cell lymphoma (MCL) is a B-cell neoplasia genetically characterized by the t(11;14)(q13;q32) translocation leading to the overexpression of its target gene CCND1. The aggressive clinical behavior of this tumor has been considered to be influenced by its genetic and molecular pathogenesis that integrates an accumulation of many chromosomal aberrations associated with frequent alterations in cell cycle and DNA damage response mechanisms and activation of cell survival pathways. Recent studies aimed to define new chromosomal regions, target genes, and signaling pathways that may contribute to the pathogenesis of this tumor. A subset of patients presenting with a leukemic and non-nodal disease and following a more indolent clinical evolution seem to have some differences in their chromo... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053728 Thu, 30 Jun 2011 23:00:00 +0100 5053728 http://www.medworm.com/index.php?rid=5053727&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000333%2Fabstract%3Frss%3Dyes Mantle cell lymphoma (MCL) is a relatively rare lymphoma, accounting for less than 10% only of all lymphomas. Its morphology is quite homogeneous, but it varies strikingly in about 10% of the cases, making the diagnosis of MCL challenging for histopathologists. The definition of the disease was greatly influenced by the discovery of the translocation t(11;14)(q13,q32), which juxtaposes the cyclin D1 and the immunoglobulin heavy chain genes and is present in the vast majority of MCL cases. The introduction of monoclonal antibodies for the detection of cyclin D1 expression into the diagnostic procedure substantially improved the reproducibility and reliability of the pathological diagnosis. However, new challenges for histopathologists have arisen over the last years, among which are the det... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053727 Thu, 30 Jun 2011 23:00:00 +0100 5053727 http://www.medworm.com/index.php?rid=5053726&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000540%2Fabstract%3Frss%3Dyes This issue of Seminars in Hematology focuses on the molecular pathogenesis and clinical management of mantle cell lymphoma (MCL), a “wanderer” within the lymphoma classifications. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053726 Thu, 30 Jun 2011 23:00:00 +0100 5053726 http://www.medworm.com/index.php?rid=5053725&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000552%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=5053725 Thu, 30 Jun 2011 23:00:00 +0100 5053725 http://www.medworm.com/index.php?rid=4645605&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000163%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645605 Tue, 29 Mar 2011 17:02:16 +0100 4645605 http://www.medworm.com/index.php?rid=4645604&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000151%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645604 Tue, 29 Mar 2011 17:02:16 +0100 4645604 http://www.medworm.com/index.php?rid=4645603&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631100014X%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645603 Tue, 29 Mar 2011 17:02:16 +0100 4645603 http://www.medworm.com/index.php?rid=4645602&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000035%2Fabstract%3Frss%3Dyes A number of human disorders, dubbed ribosomopathies, are linked to impaired ribosome biogenesis or function. These include but are not limited to Diamond Blackfan anemia (DBA), Shwachman Diamond syndrome (SDS), and the 5q- myelodysplastic syndrome (MDS). This review focuses on the latter two non-DBA disorders of ribosome function. Both SDS and 5q- syndrome lead to impaired hematopoiesis and a predisposition to leukemia. SDS, due to bi-allelic mutations of the SBDS gene, is a multi-system disorder that also includes bony abnormalities, and pancreatic and neurocognitive dysfunction. SBDS associates with the 60S subunit in human cells and has a role in subunit joining and translational activation in yeast models. In contrast, 5q- syndrome is associated with acquired haplo-insufficiency of RPS... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645602 Tue, 29 Mar 2011 17:02:16 +0100 4645602 http://www.medworm.com/index.php?rid=4645601&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000084%2Fabstract%3Frss%3Dyes Diamond Blackfan anemia (DBA) is a lineage-selective inherited bone marrow failure syndrome characterized primarily by anemia and physical malformations. Recent advances in identifying the genetic abnormalities underlying DBA have demonstrated involvement of genes encoding both large (RPL) and small (RPS) ribosomal subunit proteins, including mutations of RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 in 50% to 60% of affected patients. Despite significant progress, identification of gene abnormalities in the remaining patients remains an important question since present data suggest that mutations in other members of the ribosomal protein gene complement do not explain those cases without an identified genetic lesion in these genes. Genetic studies have also raised new q... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645601 Tue, 29 Mar 2011 17:02:16 +0100 4645601 http://www.medworm.com/index.php?rid=4645600&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000059%2Fabstract%3Frss%3Dyes Despite significant improvements in our understanding of the pathophysiology of Diamond Blackfan anemia (DBA), there have been few advances in therapy. The cornerstones of treatment remain corticosteroids, chronic red blood cell transfusions, and hematopoietic stem cell transplantation, each of which is fraught with complications. In this article, we will review the history of therapies that have been offered to patients with DBA, summarize the current standard of care, including management of side effects, and discuss novel therapeutics that are being developed in the context of the research into the roles of ribosomal haplo-insufficiency and p53 activation in Diamond Blackfan anemia. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645600 Tue, 29 Mar 2011 17:02:16 +0100 4645600 http://www.medworm.com/index.php?rid=4645599&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000060%2Fabstract%3Frss%3Dyes Diamond Blackfan anemia (DBA) is a genetic syndrome characterized by red blood cell aplasia in association with developmental abnormalities such as growth retardation, orofacial, hand or limb malformations, urogenital anomalies, and heart defects. The only known cause is heterozygosity for mutations in genes encoding ribosomal proteins. Understanding how defective ribosome biogenesis and function, important for all cells, causes defects in erythropoiesis and tissue-specific phenotypes during development is paramount to the evolution of effective treatment protocols. Here, we discuss how animal models based on mammals, insects, and fish replicate genetic or developmental aspects of DBA and have led to the identification of pathways and candidate molecules that are important in the pathogene... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645599 Tue, 29 Mar 2011 17:02:16 +0100 4645599 http://www.medworm.com/index.php?rid=4645598&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000096%2Fabstract%3Frss%3Dyes Impaired ribosome biogenesis is the underlying cause of the pathological conditions collectively known as ribosomopathies. Several hypotheses have been advanced to explain the mechanisms by which deficiencies in ribosome biogenesis interfere with developmental processes leading eventually to the emergence of these diseases. In recent years it has become clear that perturbation of this process triggers a cell-cycle checkpoint that, through activation of the tumor-suppressor p53, leads to cell-cycle arrest and apoptosis. Indeed, evidence is accumulating from studies in animal models that the unscheduled activation of p53 is responsible for perturbations in tissue homeostasis that cause the development of ribosomopathies such as Treacher-Collins syndrome (TCS) and 5q- syndrome. These findings... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645598 Tue, 29 Mar 2011 17:02:16 +0100 4645598 http://www.medworm.com/index.php?rid=4645597&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000102%2Fabstract%3Frss%3Dyes Within the decade following the demonstration that mutations in the RPS19 gene can lead to Diamond-Blackfan anemia (DBA), this disease has become a paradigm for an emerging group of pathologies linked to defects in ribosome biogenesis. DBA patients exhibit abnormal pre-rRNA maturation patterns and the majority bear mutations in one of several ribosomal protein genes that encode structural components of the ribosome essential for the correct assembly of the ribosomal subunits. Extensive study of the most frequently mutated gene, RPS19, has shown that mutations prevent the assembly of the ribosomal protein into forming pre-ribosomal particles. This defect in ribosome production triggers nucleolar stress pathways, the activation of which appears to be central to pathophysiological mechanisms.... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645597 Tue, 29 Mar 2011 17:02:16 +0100 4645597 http://www.medworm.com/index.php?rid=4645596&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000072%2Fabstract%3Frss%3Dyes Diamond Blackfan anemia (DBA) is a rare congenital anemia, with more than 50% of patients having mutations in a ribosomal protein. Evidence suggests that both translation and p53 activation play roles in mediating the hematopoietic phenotype. The reason for erythroid specificity of DBA is unclear. Several zebrafish models of DBA have been generated, and these models have already provided key information about disease pathogenesis. The zebrafish model is particularly amenable for studying blood development, allows for advanced imaging techniques, can be manipulated genetically, and is useful for high-throughput screening. By applying zebrafish approaches to the existing DBA models, we will be able to better understand the role of the ribosomal protein mutation in DBA and develop better trea... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645596 Tue, 29 Mar 2011 17:02:16 +0100 4645596 http://www.medworm.com/index.php?rid=4645595&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000023%2Fabstract%3Frss%3Dyes Over the past decade, studies of Diamond Blackfan anemia (DBA) have revealed new insights into the novel molecular pathways of this rare bone marrow disorder, and the links among defective ribosome biosynthesis, nucleolar stress, and cancer are now being refined. There is no question these scientific and clinical advancements (A and B) have improved the lives of patients and families struggling with DBA. But it has been the coming together—the communication and collaboration among all stakeholders—that has allowed such translational achievements to occur. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645595 Tue, 29 Mar 2011 17:02:16 +0100 4645595 http://www.medworm.com/index.php?rid=4645594&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000047%2Fabstract%3Frss%3Dyes Sixty years after the initial clinical description of Diamond Blackfan anemia (DBA), Niklas Dahl's group in Sweden discovered mutations in a gene encoding the ribosomal protein (RP) S19 in some patients with DBA. Initially ribosomes were felt to be so ubiquitous in tissue and perhaps too fundamental to biologic function for defects in their biogenesis or function to result in the relatively restricted and non-lethal phenotype associated with DBA. Early skepticism, keyed by the discovery of pathologic mutations in both small and large subunit associated ribosomal protein genes, has since vanished and research on DBA has surged in recent years. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645594 Tue, 29 Mar 2011 17:02:15 +0100 4645594 http://www.medworm.com/index.php?rid=4645593&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196311000138%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4645593 Tue, 29 Mar 2011 17:02:15 +0100 4645593 http://www.medworm.com/index.php?rid=4363973&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001174%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363973 Sat, 01 Jan 2011 00:00:00 +0100 4363973 http://www.medworm.com/index.php?rid=4363972&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001162%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363972 Sat, 01 Jan 2011 00:00:00 +0100 4363972 http://www.medworm.com/index.php?rid=4363971&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001150%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363971 Sat, 01 Jan 2011 00:00:00 +0100 4363971 http://www.medworm.com/index.php?rid=4363970&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001125%2Fabstract%3Frss%3Dyes Smoldering myeloma (SMM) is a precursor state of multiple myeloma. It is defined by an M-protein concentration ≥3 g/dL and/or ≥10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undetermined significance (MGUS)-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into clinical risk groups. However, due to considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Based on the International Myeloma Working Group 2010 guidelines, patients diagnosed with MGUS and SMM should not be treated outside of clinical trials. Overall, treatment ... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363970 Sat, 01 Jan 2011 00:00:00 +0100 4363970 http://www.medworm.com/index.php?rid=4363969&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001046%2Fabstract%3Frss%3Dyes Manifestations of bone disease—osteopenia, osteolytic lesions, and fractures—are the hallmark of multiple myeloma (MM) and occur clinically in the vast majority of patients. These abnormalities can have devastating clinical effects by increasing both the morbidity and mortality of patients. Bone disease is usually found when patients are diagnosed with active MM; however, recent data suggest that it is present in early myelomagenesis, including patients with myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS). The primary mechanisms of abnormal bone remodeling are increased osteoclastic activity, which occurs in close proximity to active myeloma cells, and decreased activity of the surrounding osteoblasts. Better understanding of the pathogenesis of bon... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363969 Sat, 01 Jan 2011 00:00:00 +0100 4363969 http://www.medworm.com/index.php?rid=4363968&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001058%2Fabstract%3Frss%3Dyes Patients with multiple myeloma are at an increased risk of venous thromboembolism (VTE), especially when treated with the immunomodulatory drugs, thalidomide and lenalidomide, in combination with dexamethasone and/or chemotherapy. Several studies have shown that patients with multiple myeloma precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) also have a higher risk of thrombosis compared to the general population. The underlying mechanisms for the hypercoagulable state are not completely understood. In this review, we discuss risk factors for thrombosis in multiple myeloma, as well as prophylactic strategies, the evidence for thrombosis among patients with MGUS, and proposed mechanisms for the hypercoagulability. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363968 Sat, 01 Jan 2011 00:00:00 +0100 4363968 http://www.medworm.com/index.php?rid=4363967&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001101%2Fabstract%3Frss%3Dyes microRNAs (miRNAs) are increasingly recognized as significant players in oncogenesis and tumor biology through post-transcriptional gene regulation impacting broad pathways of proliferation, differentiation, apoptosis, metastasis, and cell survival. Recent studies have found abnormal expression of miRNAs in multiple myeloma (MM). Currently, the precise role of these miRNAs in the biology of MM remains to be elucidated, although they are predicted to be involved in plasma cell proliferation, survival, homing, or in MM cell interactions with the bone marrow microenvironment. Furthermore, a limited number of studies focusing on MM precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) reveal significant differences in miRNA profiles between MGUS and normal plasma cells.... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363967 Sat, 01 Jan 2011 00:00:00 +0100 4363967 http://www.medworm.com/index.php?rid=4363966&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001083%2Fabstract%3Frss%3Dyes Flow cytometric immunophenotyping (FCM) of multiple myeloma (MM) is commonly accepted in academic centers as providing clinically significant information and is becoming increasingly utilized in the private setting. FCM has established clinical relevance in the following: (1) differential diagnosis of MM from other plasma cell dyscrasias; (2) differentiating MM from lymphoplasmacytic lymphoma (LPL) and other non-Hodgkin lymphomas; (3) diagnosis of unusual cases of myeloma (eg, to confirm the diagnosis of rare cases of IgM MM); (4) determining the risk of progression of monoclonal gammopathy of uncertain significance (MGUS) and smoldering MM; (5) prognostication in MM; and (6) minimal residual disease detection (MRD) post therapy. FCM may have an emerging role in the enumeration of abnormal... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363966 Sat, 01 Jan 2011 00:00:00 +0100 4363966 http://www.medworm.com/index.php?rid=4363965&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001095%2Fabstract%3Frss%3Dyes Multiple myeloma (MM) is consistently preceded by its pre-malignant states, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). By definition, precursor conditions do not exhibit end-organ disease (anemia, hypercalcemia, renal failure, skeletal lytic lesions, or a combination of these). However, new imaging methods are demonstrating that some patients in the MGUS or SMM category are exhibiting early signs of MM. Although MGUS/SMM patients are currently defined as low-risk versus high-risk based on clinical markers, we currently lack the ability to predict the individual patient's risk of progression from MGUS/SMM to MM. Given that the presence of gross lytic bone lesions is a hallmark of MM, it is reasonable to believe that less severe bone c... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363965 Sat, 01 Jan 2011 00:00:00 +0100 4363965 http://www.medworm.com/index.php?rid=4363964&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001071%2Fabstract%3Frss%3Dyes Plasma cell neoplasms result from the clonal expansion of terminally differentiated, immunoglobulin heavy-chain class switched B cells that typically secrete a monoclonal immunoglobulin. The 2008 World Health Organization (WHO) classification of plasma cell neoplasms encompasses a broad spectrum of disorders, from the precursor disorder monoclonal gammopathy of undetermined significance (MGUS) to plasma cell leukemia. The classification includes, in addition to precursor lesion MGUS, plasma cell myeloma, plasmacytoma, immunoglobulin deposition diseases, and osteosclerotic myeloma. Plasma cell myeloma is further divided into symptomatic plasma cell myeloma or multiple myeloma (MM), asymptomatic smoldering myeloma (SMM), non-secretory myeloma, and plasma cell leukemia. Although histopatholog... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363964 Sat, 01 Jan 2011 00:00:00 +0100 4363964 http://www.medworm.com/index.php?rid=4363963&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631000106X%2Fabstract%3Frss%3Dyes Monoclonal gammopathy of undetermined significance (MGUS), including immunoglobulin light chain only MGUS, is an age-dependent premalignant tumor that is present in about 4% of Caucasian individuals over the age of 50 years. It is comprised of two different kinds of tumors: about 15% lymphoid or lymphoplasmacytoid MGUS and the remainder plasma cell MGUS. Plasma cell MGUS is stable but can sporadically progress to multiple myeloma (MM) at an average rate of about 1% per year. Most, if not all, MM tumors are preceded by plasma cell MGUS, which shares four partially overlapping oncogenic features with MM. It presently is not possible to unequivocally distinguish an MGUS tumor cell from an MM tumor cell. However, two models based on clinical laboratory tests indicate that it is possible to str... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363963 Sat, 01 Jan 2011 00:00:00 +0100 4363963 http://www.medworm.com/index.php?rid=4363962&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001113%2Fabstract%3Frss%3Dyes This issue of Seminars in Hematology focuses on early myeloma disease. The past three decades, several studies have been conducted to better understand clinical patterns and molecular underpinnings of multiple myeloma and its precursor states. Indeed, since monoclonal gammopathy of undetermined significance (MGUS) was first described in 1978, the definition of the entity has evolved. Today, three distinct clinical MGUS subtypes have been defined: non-IgM (IgG or IgA) MGUS, IgM MGUS, and light chain MGUS. Each clinical MGUS subtype is characterized by unique intermediate stages and progression events. For example, the more advanced premalignant stage of plasma cell proliferation in non-IgM MGUS is smoldering multiple myeloma (SMM); it has an average 10% annual risk of progression to multipl... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363962 Sat, 01 Jan 2011 00:00:00 +0100 4363962 http://www.medworm.com/index.php?rid=4363961&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310001149%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4363961 Sat, 01 Jan 2011 00:00:00 +0100 4363961 http://www.medworm.com/index.php?rid=4006180&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000909%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006180 Wed, 29 Sep 2010 14:29:18 +0100 4006180 http://www.medworm.com/index.php?rid=4006179&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000892%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006179 Wed, 29 Sep 2010 14:29:18 +0100 4006179 http://www.medworm.com/index.php?rid=4006178&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000880%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006178 Wed, 29 Sep 2010 14:29:18 +0100 4006178 http://www.medworm.com/index.php?rid=4006177&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000879%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006177 Wed, 29 Sep 2010 14:29:18 +0100 4006177 http://www.medworm.com/index.php?rid=4006176&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000788%2Fabstract%3Frss%3Dyes Imatinib is considered standard frontline therapy for the management of patients with chronic myeloid leukemia (CML). However, it is estimated that approximately one third of patients will fail imatinib therapy. The recommended therapeutic approach for those patients is the use of a second-generation tyrosine kinase inhibitor (TKI) such as nilotinib or dasatinib. With these agents, approximately 50% of patients achieve a complete cytogenetic response (0% Philadelphia chromosome–positive [Ph+] bone marrow metaphases), the duration of which has not yet been established. For the remainder, the options are limited to allogeneic stem cell transplantation (SCT) or enrollment on a clinical trial with an investigational agent. Third-generation TKIs and non-adenosine triphosphate (non-ATP) mimeti... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006176 Wed, 29 Sep 2010 14:29:18 +0100 4006176 http://www.medworm.com/index.php?rid=4006175&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000806%2Fabstract%3Frss%3Dyes Chronic myeloid leukemia (CML) is a clonal multistep myeloproliferative disease originating from and ultimately sustained by a rare population of BCR-ABL+ cells with multilineage stem cell properties. Imatinib, the most successful of molecular targeted therapies, has revolutionized treatment of patients with CML. Despite this achievement, CML is often not curable, largely due to the innate insensitivity of CML stem cells, particularly when in a quiescent state. This failure of not only imatinib but also the second-generation tyrosine kinase inhibitors (TKIs) frequently leads to relapse upon drug discontinuation. Thus, any curative therapy must eliminate CML stem cells. A comprehensive understanding of the biological properties of CML stem cells and an elucidation of the molecular mechanism... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006175 Wed, 29 Sep 2010 14:29:17 +0100 4006175 http://www.medworm.com/index.php?rid=4006174&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631000082X%2Fabstract%3Frss%3Dyes This article reviews the data on the variables that influence outcome following transplantation, and discusses the variables to consider in determining which patients should receive transplantation and when. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006174 Wed, 29 Sep 2010 14:29:17 +0100 4006174 http://www.medworm.com/index.php?rid=4006173&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000764%2Fabstract%3Frss%3Dyes Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006173 Wed, 29 Sep 2010 14:29:17 +0100 4006173 http://www.medworm.com/index.php?rid=4006172&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631000079X%2Fabstract%3Frss%3Dyes Mechanisms of resistance to the tyrosine kinase inhibitor (TKI) imatinib had been modeled in vitro even prior to the first reports of clinical resistance in patients with chronic myeloid leukemia (CML). The discovery that BCR-ABL is reactivated at the time of resistance and the unveiling of point mutations within the kinase domain of BCR-ABL as a major resistance mechanism have driven the development of second-generation TKIs. These agents are effective in a significant proportion of patients who fail to respond to imatinib. Clinical practice guidelines recommend using the BCR-ABL mutation genotype to aid selection of second-line treatment. Although kinase domain mutations are undoubtedly relevant to drug resistance, recent data suggest that additional resistance mechanisms must be operati... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006172 Wed, 29 Sep 2010 14:29:17 +0100 4006172 http://www.medworm.com/index.php?rid=4006171&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000818%2Fabstract%3Frss%3Dyes Current routine monitoring strategies for chronic myeloid leukemia (CML) incorporate hematologic, cytogenetic, and molecular analysis. BCR-ABL1 kinase domain mutation analysis is an important assessment in specific circumstances. The recommendations for when and how frequently to undertake these assessments have recently been updated. However, response assessment is not always straightforward and access to some analytical tools may not be available. Pharmacokinetic assessment of imatinib levels may correlate with clinical response and could help in assessing issues of suboptimal response, excessive toxicity, or noncompliance. Here we provide practical considerations for monitoring response, offer suggestions for alternative assessments in case of failure or limited access of analyses, and ... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006171 Wed, 29 Sep 2010 14:29:17 +0100 4006171 http://www.medworm.com/index.php?rid=4006170&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000752%2Fabstract%3Frss%3Dyes Although imatinib is presently the treatment of choice in newly diagnosed chronic-phase (CP) chronic myeloid leukemia (CML) patients, 8 years from start of the International Randomized Study of Interferon and STI571 (IRIS) trial, 45% of the patients originally enrolled in the imatinib arm (imatinib 400 mg/d) have discontinued this treatment; in 15% of the cases this was due to lack of efficacy and in 5% for safety or intolerance problems. With the aim of improving the results of the standard imatinib 400 mg/d first-line therapy of CML, several trials have been started and are presently ongoing. The purpose of these trials is to test the efficacy of higher dosages of imatinib and of imatinib in combination with other agents, in particular with interferon alpha (IFN). In addition, second-gen... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006170 Wed, 29 Sep 2010 14:29:17 +0100 4006170 http://www.medworm.com/index.php?rid=4006169&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000776%2Fabstract%3Frss%3Dyes Imatinib is remarkably effective in treating newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase. However, at 5 years more than one third of the patients have abandoned the medication on account of side effects, lack of efficacy, or progression. Here we review the current results with imatinib, the prognostic factors for response, and issues associated with long-term treatment with imatinib such as pregnancy, adherence to therapy, and complete molecular responses. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006169 Wed, 29 Sep 2010 14:29:17 +0100 4006169 http://www.medworm.com/index.php?rid=4006168&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000831%2Fabstract%3Frss%3Dyes Patients with splenomegaly and abnormally high leukocyte counts were first recognized in France, Germany, and Scotland in the 1840s. The only well-documented therapy in the 19th century was use of arsenic in one or other form, which did undoubtedly reduce the leukocyte count but probably did little or nothing to prolong life. These early cases were probably examples of chronic myeloid leukemia (CML) (then called chronic granulocytic leukemia). In the 20th century important steps in unraveling the pathogenesis of CML were the discovery of the Philadelphia chromosome in 1960, and of the (9;22) translocation in 1973. There followed definition of the breakpoint cluster region on chromosome 22 in 1984 and the demonstration of the BCR-ABL transcript in CML in 1985. In the first half of the 20th ... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006168 Wed, 29 Sep 2010 14:29:17 +0100 4006168 http://www.medworm.com/index.php?rid=4006167&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000843%2Fabstract%3Frss%3Dyes The advances in understanding the biology of chronic myeloid leukemia (CML), and translating this knowledge to the development of specific therapy that is highly effective, are unprecedented in cancer medicine. In just a few years, the natural history of the disease has been changed in a rather dramatic way and new developments, which occur at a surprisingly rapid pace, continue to improve the expected outcome of patients. It is now 50 years since the initial observation of a minute chromosome present in patients with this disease, and the genial suggestion that there was, in the words of Nowell and Hungenford, “a causal relationship between the chromosomal abnormality observed and chronic granulocytic leukemia.” This abnormality was later identified as a balanced translocation between... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=4006167 Wed, 29 Sep 2010 14:29:17 +0100 4006167 http://www.medworm.com/index.php?rid=3681520&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000661%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681520 Tue, 22 Jun 2010 05:48:47 +0100 3681520 http://www.medworm.com/index.php?rid=3681519&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631000065X%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681519 Tue, 22 Jun 2010 05:48:47 +0100 3681519 http://www.medworm.com/index.php?rid=3681518&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000648%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681518 Tue, 22 Jun 2010 05:48:47 +0100 3681518 http://www.medworm.com/index.php?rid=3681517&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000430%2Fabstract%3Frss%3Dyes The objective of this review is to describe the reported and potential toxicities of the TGFs, including bone marrow fibrosis, thrombosis, rebound thrombocytopenia, hematologic malignancy, neutralizing antibody formation, hepatotoxicity, cataract formation, and common adverse events. The incidence and clinical implications of these toxicities as well as strategies for patient safety monitoring are examined. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681517 Tue, 22 Jun 2010 05:48:46 +0100 3681517 http://www.medworm.com/index.php?rid=3681516&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000582%2Fabstract%3Frss%3Dyes Thrombocytopenia is common among sick neonates, affecting 20% to 35% of all patients admitted to the neonatal intensive care unit (NICU). While most cases of neonatal thrombocytopenia are mild or moderate and resolve within 7 to 14 days with appropriate therapy, 2.5% to 5% of NICU patients develop severe thrombocytopenia, sometimes lasting for several weeks and requiring >20 platelet transfusions. The availability of thrombopoietic agents offers the possibility of decreasing the number of platelet transfusions and potentially improving the outcomes of these infants. However, adding thrombopoietin (TPO) mimetics to the therapeutic armamentarium of neonatologists will require careful attention to the substantial developmental differences between neonates and adults in the process of megakary... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681516 Tue, 22 Jun 2010 05:48:46 +0100 3681516 http://www.medworm.com/index.php?rid=3681515&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000314%2Fabstract%3Frss%3Dyes Thrombocytopenia, common in leukemias and myelodysplastic syndromes (MDS), is responsible for increased risk of bleeding and delay of therapy. Platelet transfusions, although effective in increasing platelet counts, are limited by supply, are associated with risks, and result in limited and transient benefits. Successful development of an alternative treatment approach with thrombopoietin agonists was nearly thwarted when early formulations of recombinant thrombopoietin agonists elicited antibodies that cross-reacted with and neutralized endogenous thrombopoietin. The effectiveness of these recombinant agents led to the development of second-generation thrombopoietin receptor agonists that do not induce cross-reacting neutralizing antibodies against thrombopoietin. Two of the novel thrombo... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681515 Tue, 22 Jun 2010 05:48:46 +0100 3681515 http://www.medworm.com/index.php?rid=3681514&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000594%2Fabstract%3Frss%3Dyes Thrombocytopenia can be a sign of advanced liver disease. This complicates the management of these patients, as patients with advanced liver disease frequently need therapeutic interventions, which are associated with an increased risk of bleeding. Thrombocytopenia may even be more pronounced in patients with hepatitis C virus (HCV) infection. This can limit current and future treatments for HCV, which remains based on interferon therapy, and this therapy can worsen thrombocytopenia. Thus, the ability to increase platelets to higher and safer levels would be desirable, but no treatment has yet been proven effective and safe in this setting. The small molecule thrombopoietin mimetic, eltrombopag, has demonstrated a dose-response increase in platelet counts in a phase II study in HCV patient... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681514 Tue, 22 Jun 2010 05:48:46 +0100 3681514 http://www.medworm.com/index.php?rid=3681513&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000442%2Fabstract%3Frss%3Dyes Immune thrombocytopenia (ITP) is a disease characterized by accelerated platelet destruction and suboptimal platelet production. The latter concept has led to the exploration of new therapeutic options by focusing on the stimulation of platelet production as opposed to the traditional approach of immune suppression. Thrombopoietic agents act by stimulating the thrombopoietin receptor on the hematopoietic cells leading to stem cell differentiation, megakaryocyte proliferation, and platelet production. The last decade has witnessed the birth of second-generation thrombopoietic agents. Romiplostim and eltrombopag are the two agents that have been recently licensed. In randomized controlled trials, these agents have demonstrated unequivocal superiority over placebo in the treatment of ITP in s... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681513 Tue, 22 Jun 2010 05:48:46 +0100 3681513 http://www.medworm.com/index.php?rid=3681512&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000454%2Fabstract%3Frss%3Dyes Thrombocytopenia is a common problem in hematology/oncology patients. In the past two decades a number of thrombopoietic growth factors and related cytokines have become available for clinical investigations. Unfortunately, most of the pleiotropic cytokines have been limited by their modest activity and toxicity profile. The discovery of thrombopoietin (TPO), a key regulator of platelet production, led to the clinical development of two recombinant versions of the molecule: full-length, recombinant human thrombopoietin (rhTPO), and truncated and pegylated, megakaryocyte growth and development factor (Peg-rHuMGDF). Both agents showed significant biologic activity in various clinical settings, including nonmyeloablative chemotherapy, mobilization of progenitors, platelet apheresis, and treat... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681512 Tue, 22 Jun 2010 05:48:46 +0100 3681512 http://www.medworm.com/index.php?rid=3681511&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000302%2Fabstract%3Frss%3Dyes Endogenous thrombopoietin (eTPO) regulates platelet production by increasing the number, ploidy, and maturation rate of bone marrow megakaryocytes. Early attempts to treat thrombocytopenia by the administration of recombinant TPO were successful but were complicated by the development of antibodies to one of the recombinant proteins. Two new TPO mimetics have recently been approved by the US Food and Drug Administration (FDA) for the treatment of immune thrombocytopenia (ITP). Romiplostim is a peptide TPO mimetic composed of an IgG Fc fragment to which are attached four 14–amino acid TPO peptides that activate the TPO receptor by binding to the extracytoplasmic domain just like eTPO. Romiplostim is administered as a weekly subcutaneous injection. Eltrombopag, a nonpeptide TPO mimetic, is... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681511 Tue, 22 Jun 2010 05:48:46 +0100 3681511 http://www.medworm.com/index.php?rid=3681510&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000570%2Fabstract%3Frss%3Dyes Most platelet transfusions are given to prevent bleeding in thrombocytopenic patients undergoing chemotherapy for malignancy or hematopoietic stem cell transplant. In stable, uncomplicated patients the risk of bleeding is similar until the platelet count falls to (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681510 Tue, 22 Jun 2010 05:48:46 +0100 3681510 http://www.medworm.com/index.php?rid=3681509&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000478%2Fabstract%3Frss%3Dyes It is becoming increasingly clear that most mammalian cells are capable of undergoing apoptosis and that, within particular lineages, specific apoptotic pathways have evolved to regulate survival and turnover. The role of apoptosis in the megakaryocyte lineage is an intriguing one. Various insults, such as chemotherapeutics, autoantibodies, and human immunodeficiency virus (HIV), have been suggested to induce the apoptotic death of megakaryocytes and/or their progenitors. Conversely, apoptotic processes have been implicated in megakaryocyte development and platelet production. Platelets also contain functional apoptotic pathways, which circumscribe their survival. It has even been suggested that platelet activation responses involve components of the apoptotic machinery, highlighting a pot... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681509 Tue, 22 Jun 2010 05:48:46 +0100 3681509 http://www.medworm.com/index.php?rid=3681508&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000466%2Fabstract%3Frss%3Dyes Thrombocytopenia is the underlying cause of a number of major clinical conditions and genetic disorders worldwide. While therapeutic agents that bind and stimulate the thrombopoietin receptor are currently available, the development of drugs that directly stimulate megakaryocytes to generate platelets has lagged behind. To improve the management of thrombocytopenia, we will need to define the cell biological pathways that drive the production of platelets from megakaryocytes. This review integrates the latest research of platelet biogenesis and focuses on the molecular pathways that power and regulate proplatelet production. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681508 Tue, 22 Jun 2010 05:48:46 +0100 3681508 http://www.medworm.com/index.php?rid=3681507&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000326%2Fabstract%3Frss%3Dyes The process of megakaryopoiesis and platelet production is complex, with the potential for regulation at multiple stages. Megakaryocytes are derived from the hematopoietic stem cell through successive lineage commitment steps, and they undergo a unique maturation process that includes polyploidization, development of an extensive internal demarcation membrane system, and finally formation of pro-platelet processes. Platelets are shed from these processes into vascular sinusoids within the bone marrow. Megakaryocyte differentiation is regulated both positively and negatively by transcription factors and cytokine signaling. Thrombopoietin (TPO) is the most important hematopoietic cytokine for platelet production. Clinically, acquired and inherited mutations affecting megakaryocytic transcrip... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681507 Tue, 22 Jun 2010 05:48:45 +0100 3681507 http://www.medworm.com/index.php?rid=3681506&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000600%2Fabstract%3Frss%3Dyes This Seminars in Hematology issue on thrombopoietic agents and thrombocytopenia spans a wide spectrum of topics in the field. It begins with the biology of megakaryocytopoiesis and thrombocytopoiesis. This includes a discussion of the factors regulating development of megakaryocytes (Geddis) but also the exciting new developments from the work by Italiano's group on the formation of platelets and that of Ben Kile on the emerging role of platelet apoptosis in the determination of platelet lifespan. Going more to the clinical, background chapters include the current use of platelet transfusions by McCullough, the discovery of thrombopoietin and development of thrombopoietic agents by Kuter, and a discussion combining laboratory and clinical aspects of fetal and neonatal megakaryocytopoiesis.... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681506 Tue, 22 Jun 2010 05:48:45 +0100 3681506 http://www.medworm.com/index.php?rid=3681505&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000636%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3681505 Tue, 22 Jun 2010 05:48:45 +0100 3681505 http://www.medworm.com/index.php?rid=3417764&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000272%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417764 Tue, 30 Mar 2010 13:31:21 +0100 3417764 http://www.medworm.com/index.php?rid=3417763&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000260%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417763 Tue, 30 Mar 2010 13:31:21 +0100 3417763 http://www.medworm.com/index.php?rid=3417762&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000089%2Fabstract%3Frss%3Dyes Targeting the CD20 antigen on B lymphocytes with the monoclonal antibody (MoAb) rituximab has greatly improved the outcome of patients with B-cell malignancies. Despite the success of rituximab, resistance occurs in about half of the patients, resulting in non-response to treatment or early relapse with the original disease. A better understanding of the mechanism of rituximab resistance has led to the development of novel, improved anti-CD20 antibodies. This review describes the development of CD20-targeted therapy from its historical background towards the next generation of anti-CD20 MoAbs and explains new strategies to overcome resistance. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417762 Tue, 30 Mar 2010 13:31:21 +0100 3417762 http://www.medworm.com/index.php?rid=3417761&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719631000003X%2Fabstract%3Frss%3Dyes After more than 10 years of use, rituximab has proven to be remarkably safe. However, accumulated evidence now suggests that under some circumstances it may significantly increase the risk of infections. This risk is difficult to quantify because of confounding factors (namely, concomitant use of immunosuppressive or chemotherapeutic agents and underlying conditions), as well as under-reporting. Increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by human immunodeficiency virus (HIV) infection or immunosuppressive agents like fludarabine. From the practical standpoint, the most important infection is hepatitis B reactivation, which may be delayed and... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417761 Tue, 30 Mar 2010 13:31:20 +0100 3417761 http://www.medworm.com/index.php?rid=3417760&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000107%2Fabstract%3Frss%3Dyes Several recent studies have reported the phenomenon of late-onset neutropenia occurring usually several months following the administration of rituximab or rituximab-based therapies. While it appears that late-onset neutropenia is usually not clinically significant and is self-limited, it is important to recognize its existence given the expanding use of rituximab in both hematologic and nonhematologic disorders. Late-onset neutropenia is intriguing biologically and while its pathogenesis and mechanism are not completely understood, many interesting hypotheses have been proposed to explain its occurrence. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417760 Tue, 30 Mar 2010 13:31:20 +0100 3417760 http://www.medworm.com/index.php?rid=3417759&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000119%2Fabstract%3Frss%3Dyes Rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen, has been investigated extensively in autoimmune disorders. Following the encouraging results in immune thrombocytopenia (ITP), the use of this agent was explored in other autoimmune hematologic diseases, most notably autoimmune hemolytic anemia (AIHA) and thrombotic thrombocytopenic purpura (TTP), characterized by the presence of pathogenetic autoantibodies. Although randomized clinical trials are lacking, the cumulative data would suggest that rituximab has a beneficial role in their treatment. Response to B-cell–depleting therapy is actually associated with a significant decrease of circulating autoantibodies. However, several lines of evidence indicate that the T-cell compartme... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417759 Tue, 30 Mar 2010 13:31:20 +0100 3417759 http://www.medworm.com/index.php?rid=3417758&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000065%2Fabstract%3Frss%3Dyes Rituximab is a class I chimeric anti-CD20 antibody that has shown efficacy in chronic lymphocytic leukemia (CLL), both as a single agent and in combination with traditional chemotherapies. The modest activity demonstrated in early studies evaluating rituximab in relapsed CLL was improved with higher doses or more dose-intensive regimens that overcame the unfavorable pharmacokinetic features commonly found in CLL. These studies led to a variety of combination trials of rituximab with chemotherapy, where both phase II and later phase III studies have shown great promise for the advancement of CLL therapy. Despite the therapeutic success of rituximab in CLL, studies demonstrating the definitive relative mechanism of tumor clearance are still lacking and this requires further investigation. In... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417758 Tue, 30 Mar 2010 13:31:20 +0100 3417758 http://www.medworm.com/index.php?rid=3417757&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000090%2Fabstract%3Frss%3Dyes In 1997, the approval of the anti-CD20 antibody rituximab heralded a new era of combined immunochemotherapy for the treatment of malignant lymphoma. Until then, a combination of cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) had been the standard of treatment for aggressive B-cell lymphoma for more than 25 years. The addition of rituximab led to an impressive improvement of response rates and survival outcomes in patients with follicular and diffuse large B-cell lymphoma (DLBCL) that has been confirmed in several randomized trials. Remaining challenges in the rituximab era are the identification of the optimal chemotherapy partner with respect to synergistic effects, as well as to the lack of interference with its effector mechanisms. Finally, the question of the optimal... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417757 Tue, 30 Mar 2010 13:31:20 +0100 3417757 http://www.medworm.com/index.php?rid=3417756&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000053%2Fabstract%3Frss%3Dyes Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417756 Tue, 30 Mar 2010 13:31:20 +0100 3417756 http://www.medworm.com/index.php?rid=3417755&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000041%2Fabstract%3Frss%3Dyes Indolent non-Hodgkin lymphoma (NHL) comprises a group of incurable, generally slow-growing lymphomas highly responsive to initial therapy, with a relapsing and progressive course. Rituximab, an anti-CD20 antibody, has had a large impact on the treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials, as well as data from the National Cancer Institute, indicate that the overall survival (OS) of patients with indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, rituximab is currently being investigated as a maintenance agent with encouraging results. This review summarizes several ... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417755 Tue, 30 Mar 2010 13:31:20 +0100 3417755 http://www.medworm.com/index.php?rid=3417754&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000077%2Fabstract%3Frss%3Dyes Several types of B-cell lymphoma have been successfully treated with rituximab, and approval by the US Food and Drug Administration for use of rituximab in the treatment of rheumatoid arthritis has increased interest in targeting CD20 on B cells for other indications. Although large amounts of rituximab can be infused into humans with no apparent dose-limiting toxicity, recent evidence suggests that the body's effector mechanisms, including complement-mediated cytotoxicity and natural killer (NK) cell-mediated killing, can be saturated or exhausted at high burdens of rituximab-opsonized B cells. One of the consequences of this saturation phenomenon is that the opsonized B cells are instead processed by a different pathway mediated by FcγR on effector cells. In this alternative pathway, bo... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417754 Tue, 30 Mar 2010 13:31:20 +0100 3417754 http://www.medworm.com/index.php?rid=3417753&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000120%2Fabstract%3Frss%3Dyes Rituximab is a mainstay in the therapy for a broad variety of B-cell malignancies. Despite its undeniable therapeutic value, we still do not fully understand the mechanisms of action responsible for rituximab's anti-tumor effects. Direct signaling, complement-mediated cytotoxicity (CMC), and antibody-dependent cellular cytotoxicity (ADCC) all appear to play a role in rituximab efficacy. In vitro, animal model and clinical data addressing each of these mechanisms of action are reviewed, as are data speaking to the complexity of interactions between these mechanisms. Taken together, these data suggest different mechanisms are likely important in different scenarios. Study of the complex mechanisms of action that contribute to the clinical efficacy of rituximab have led to novel clinical tria... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417753 Tue, 30 Mar 2010 13:31:20 +0100 3417753 http://www.medworm.com/index.php?rid=3417752&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000028%2Fabstract%3Frss%3Dyes The last decade has seen the monoclonal antibody (mAb), rituximab, transform clinical management of many non-Hodgkin lymphomas and more recently provide new opportunities for controlling autoimmune conditions, such as rheumatoid arthritis. Although not yet fully determined, the explanation for this success appears to lie with the inherent properties of its target, CD20, which allow rituximab to recruit potent cytotoxic effectors with unusual efficiency. In this review we detail the properties of CD20 that make it such an effective therapeutic target and describe how different mAbs change the membrane distribution and internalization of CD20 and have distinct modes of cytotoxic activity. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417752 Tue, 30 Mar 2010 13:31:20 +0100 3417752 http://www.medworm.com/index.php?rid=3417751&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196310000211%2Fabstract%3Frss%3Dyes On November 26, 1997, a little known monoclonal antibody called rituximab was approved by the US Food and Drug Administration for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL). Over a decade later, rituximab has become one of the biggest therapeutic advancements in the treatment of lymphoid malignancies, redefining the standard of care for a vast majority of B-cell neoplasms. Both as a single agent and in combination with cytotoxic chemotherapy, rituximab has significantly improved response rates and progression-free survival in a variety of lymphoid malignancies, as well as overall survival and cure rates in aggressive NHL. Rituximab has also demonstrated considerable utility in a number of autoimmune hematologic and rheumatologic diseases, and is increasingly being turn... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3417751 Tue, 30 Mar 2010 13:31:20 +0100 3417751 http://www.medworm.com/index.php?rid=3125438&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001498%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125438 Tue, 29 Dec 2009 14:23:06 +0100 3125438 http://www.medworm.com/index.php?rid=3125437&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001486%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125437 Tue, 29 Dec 2009 14:23:06 +0100 3125437 http://www.medworm.com/index.php?rid=3125436&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001474%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125436 Tue, 29 Dec 2009 14:23:06 +0100 3125436 http://www.medworm.com/index.php?rid=3125435&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001334%2Fabstract%3Frss%3Dyes The field of cord blood transplantation has come a long way since the first transplant more than 20 years ago. Advancements in the field will require continuing efforts to better understand hematopoietic stem and progenitor cell function and engraftment. Cautious optimism is inherent in the potential relevance and applicability of nonhematopoietic stem and progenitor cell types found in cord blood, and induced pluripotent stem cells generated from cord blood cells. Rigorous investigations and close interactions between scientific and clinical investigators are required to translate human in vitro and animal in vivo findings into clinical utility. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125435 Tue, 29 Dec 2009 14:23:06 +0100 3125435 http://www.medworm.com/index.php?rid=3125434&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001413%2Fabstract%3Frss%3Dyes The development of newer strategies to overcome, in particular, the cell dose limitation, has increased the availability of umbilical cord blood (UCB) as a source of hematopoietic stem cells (HSC) for transplantation of adults. Among these strategies is the development of the double UCB, ex vivo, and reduced-intensity transplantation platforms. Several ongoing registry-based and single-institution and multicenter clinical trials are investigating ways to make UCB transplantation safer and to improve the outcomes of adults after UCB transplantation. We review the background data and promising newer strategies that will further expand the utilization of UCB for the treatment of adults. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125434 Tue, 29 Dec 2009 14:23:06 +0100 3125434 http://www.medworm.com/index.php?rid=3125433&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001322%2Fabstract%3Frss%3Dyes Primary immune deficiencies (PIDs) are rare diseases, and most are lethal without appropriate intervention. Hematopoietic cell transplantation (HCT) can cure the majority of patients, but most lack a suitable matched related donor. Alternative donor stem cells (mismatched related donor bone marrow, unrelated donor bone marrow, and unrelated donor umbilical cord blood [UCB]) are therefore frequently required. Published data comparing outcomes after alternative donor transplant for PID are scarce. The outcomes and potential advantage and disadvantages of each alternative stem cell source are discussed in this chapter. Although there are insufficient prospective data to make meaningful comparisons between the alternative stem cell sources, the results presented here demonstrate clearly that t... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125433 Tue, 29 Dec 2009 14:23:06 +0100 3125433 http://www.medworm.com/index.php?rid=3125432&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001371%2Fabstract%3Frss%3Dyes Hematopoietic stem cell transplantation (HSCT) has been used for three decades as therapy for lysosomal storage diseases. Stable engraftment following transplantation has the potential to provide a source of an enzyme for the life of a patient. Recombinant enzyme is available for disorders that do not have a primary neurologic component. However, for diseases affecting the central nervous system (CNS), intravenous enzyme is ineffective due to its inability to cross the blood-brain barrier. For selected lysosomal disorders, including metachromatic leukodystrophy and globoid cell leukodystrophy, disease phenotype and the extent of disease at the time of transplantation are of fundamental importance in determining outcomes. Adrenoleukodystrophy is an X-linked, peroxisomal disorder, and in app... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125432 Tue, 29 Dec 2009 14:23:06 +0100 3125432 http://www.medworm.com/index.php?rid=3125431&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001395%2Fabstract%3Frss%3Dyes The mucopolysaccharidoses (MPSs) are inherited metabolic disorders (IMDs) caused by single-gene defects leading to progressive cellular accumulation of glycosaminoglycans (GAGs) and damage to multiple organs, including the central nervous, musculoskeletal, cardiorespiratory, and other systems. Hurler syndrome (MPS IH), the most severe form, is the prototypical model. Enzyme replacement therapy (ERT), available for MPS I, II, and VI, is beneficial in some patients. However, ERT does not improve neurocognitive function because of its inability to cross the blood-brain barrier. In contrast, allogeneic hematopoietic stem cell transplantation (HSCT) allows donor-derived, enzyme-producing cells to migrate to the brain and other organs to provide permanent enzyme therapy and thus help somatic org... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125431 Tue, 29 Dec 2009 14:23:06 +0100 3125431 http://www.medworm.com/index.php?rid=3125430&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719630900136X%2Fabstract%3Frss%3Dyes Currently, it is possible to find a hematopoietic stem cell (HSC) donor for virtually all patients with acute leukemia who have an indication to receive an allogeneic hematopoietic stem cell transplant (HSCT) and lack a human leukocyte antigen (HLA)-identical sibling or a well-matched HLA unrelated donor (URD). According to the ethnicity of the patients and the donor registry, approximately 25% to 60% of patients will not find an 8/8 HLA-matched unrelated donor. Other alternative donors, such as HLA-mismatched related donor or unrelated donor umbilical cord blood (UCB), have emerged to solve the lack of a sibling or well-matched URD. In the haploidentical HSCT setting, new techniques of T-cell depletion, new approaches using combinations of immunosuppressive drugs or different conditioning... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125430 Tue, 29 Dec 2009 14:23:06 +0100 3125430 http://www.medworm.com/index.php?rid=3125429&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001383%2Fabstract%3Frss%3Dyes Umbilical cord blood (UCB) has gradually emerged over the last decade as an alternative source of hematopoietic cells for transplantation in children and adults with high-risk or advanced hematologic malignancies who do not have a suitably matched related or unrelated adult donor. This increase in use of UCB is due to favorable results in children, growing availability of UCB units with large cell doses, less stringent donor–recipient HLA matching, and rapid identification and acquisition of the unit. In children with acute leukemia, the data support similar leukemia-free survival after transplantation of human leukocyte antigen (HLA)-matched and one or two HLA-mismatched UCB and HLA-matched unrelated donor bone marrow. In adults with acute leukemia, some reports suggest a survival advan... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125429 Tue, 29 Dec 2009 14:23:05 +0100 3125429 http://www.medworm.com/index.php?rid=3125428&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001358%2Fabstract%3Frss%3Dyes Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potential cure for most bone marrow (BM) failure syndromes and hemoglobinopathies. Over the past decade, umbilical cord blood (UCB) has been used more frequently as a stem cell source in patients who lack a suitable BM donor. Although graft failure remains a significant problem, UCB transplantation (UCBT) using the optimal conditioning regimen can be a salvage treatment for patients without a suitable BM donor and warrants evaluation in further prospective studies. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125428 Tue, 29 Dec 2009 14:23:05 +0100 3125428 http://www.medworm.com/index.php?rid=3125427&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001401%2Fabstract%3Frss%3Dyes This review highlights the unique features of immune reconstitution following unrelated cord blood transplantation (UCBT) that lead to heightened risk of infection-related mortality in the early post-UCBT period. There is no evidence that innate immunity is uniquely compromised after UCBT, but the development of antigen-specific cellular immunity is affected by numerical and qualitative deficits, primarily within the first 100 days. Nevertheless, beyond the first few months after UCBT there is no evidence for reduced graft-versus-leukemia (GVL) or anti-viral immunity compared to other hematopoietic cell therapy (HCT) modalities. Novel cellular therapies that are about to enter the clinical setting in the form of natural killer (NK) cell and T-cell therapies in the form of donor lymphocyte ... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125427 Tue, 29 Dec 2009 14:23:05 +0100 3125427 http://www.medworm.com/index.php?rid=3125426&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001346%2Fabstract%3Frss%3Dyes The aims of this review are to summarize the relevant published literature regarding cord blood (CB) graft characteristics and their impact on transplantation outcomes, to present new analyses from patients transplanted with CB units from the New York Blood Center's National Cord Blood Program, and to propose new guidelines for prioritizing CB unit selection. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125426 Tue, 29 Dec 2009 14:23:05 +0100 3125426 http://www.medworm.com/index.php?rid=3125425&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001425%2Fabstract%3Frss%3Dyes In October 1988, the world's first umbilical cord blood transplant (UCBT) was performed. Despite considerable skepticism initially by both scientists and clinical specialists in the field, umbilical cord blood (UCB) has now become one of the most commonly used sources of hematopoietic stem cells (HSCs) for allogeneic transplantation. Today, an estimated 600,000 UCB units have been banked and 20,000 UCB units have been distributed worldwide for both adults and children with life-threatening malignant and nonmalignant diseases. During this first generation of UCBT, substantial advances have been made resulting in better outcomes for our patients. UCB serves as an extraordinary example of translational medicine at its best, where clinical problems compel scientists to move basic discoveries i... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125425 Tue, 29 Dec 2009 14:23:05 +0100 3125425 http://www.medworm.com/index.php?rid=3125424&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001437%2Fabstract%3Frss%3Dyes October 24, 2008 marked the 20th anniversary of the first umbilical cord blood (UCB) transplant performed in Paris in a child with Fanconi anemia. Since that time, an estimated 20,000 transplants have been performed with about half in adults. Despite considerable early skepticism, UCB is now routinely and widely used. This edition of Seminars in Hematology was devoted to UCB because of the substantial accomplishments made in this field over the past two decades. Not only has UCB become an accepted source of hematopoietic stem cells (HSC) for transplantation, new uses as lymphoid effector cells and non-hematopoietic stem cells promise to expand its application well beyond that of classic blood and marrow transplant. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125424 Tue, 29 Dec 2009 14:23:05 +0100 3125424 http://www.medworm.com/index.php?rid=3125423&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001462%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=3125423 Tue, 29 Dec 2009 14:23:05 +0100 3125423 http://www.medworm.com/index.php?rid=2837298&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001103%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837298 Mon, 28 Sep 2009 16:46:59 +0100 2837298 http://www.medworm.com/index.php?rid=2837297&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001097%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837297 Mon, 28 Sep 2009 16:46:59 +0100 2837297 http://www.medworm.com/index.php?rid=2837296&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001152%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837296 Mon, 28 Sep 2009 16:46:59 +0100 2837296 http://www.medworm.com/index.php?rid=2837295&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001218%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837295 Mon, 28 Sep 2009 16:46:59 +0100 2837295 http://www.medworm.com/index.php?rid=2837294&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309000985%2Fabstract%3Frss%3Dyes Anemia of chronic disease, also called anemia of inflammation, is characterized by hypoferremia due to iron sequestration that eventually results in iron-restricted erythropoiesis. During the last decade, the molecular mechanisms of iron sequestration have been found to center on cytokine-stimulated overproduction of the iron-regulatory hormone hepcidin. The inflammatory cytokine interleukin-6 (IL-6) is a particularly prominent inducer of hepcidin, but other cytokines are likely to contribute as well. Hepcidin excess causes the endocytosis and proteolysis of the sole known cellular iron exporter, ferroportin, trapping iron in macrophages and iron-absorbing enterocytes. The supply of iron to hemoglobin synthesis becomes limiting, eventually resulting in anemia. Depending on the details of t... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837294 Mon, 28 Sep 2009 16:46:59 +0100 2837294 http://www.medworm.com/index.php?rid=2837293&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001036%2Fabstract%3Frss%3Dyes Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder characterized by iron deficiency anemia unresponsive to oral iron treatment but partially responsive to parenteral iron therapy. IRIDA has recently been shown to be caused by mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (also known as matriptase-2) expressed by the liver. IRIDA patients show inappropriately elevated levels of hepcidin, a circulating hormone produced by the liver that inhibits both iron absorption from the intestine and iron release from macrophage stores. Recent studies suggest that TMPRSS6 normally acts to downregulate hepcidin expression by cleaving hemojuvelin, a membrane-bound protein that promotes hepcidin signaling in hepatocytes. A discussion of the clin... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837293 Mon, 28 Sep 2009 16:46:58 +0100 2837293 http://www.medworm.com/index.php?rid=2837292&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001048%2Fabstract%3Frss%3Dyes Inherited sideroblastic anemia comprises several rare anemias due to heterogeneous genetic lesions, all characterized by the presence of ringed sideroblasts in the bone marrow. This morphological aspect reflects abnormal mitochondrial iron utilization by the erythroid precursors. The most common X-linked sideroblastic anemia (XLSA), due to mutations of the first enzyme of the heme synthetic pathway, delta-aminolevulinic acid synthase 2 (ALAS2), has linked heme deficiency to mitochondrial iron accumulation. The identification of other genes, such as adenosine triphosphate (ATP) binding cassette B7 (ABCB7) and glutaredoxin 5 (GLRX5), has strengthened the role of iron sulfur cluster biogenesis in sideroblast formation and revealed a complex interplay between pathways of mitochondrial iron uti... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837292 Mon, 28 Sep 2009 16:46:58 +0100 2837292 http://www.medworm.com/index.php?rid=2837291&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001024%2Fabstract%3Frss%3Dyes Divalent metal transporter 1 (DMT1) is the protein that allows elemental iron entry into the duodenal cell. It is expressed ubiquitously and it also allows the iron exit from the endosomes. This protein plays a central role in iron metabolism and it is strictly regulated. Several animal models elucidate its role in physiology. Recently three patients affected with DMT1 deficiency have been described. This recessively inherited condition appears at birth with severe microcytic anemia. Serum markers could be particularly useful to establish a correct diagnosis: high serum iron, normal total iron-binding capacity (TIBC), increased saturation of transferrin (Tf), slightly elevated ferritin, and increased soluble transferrin receptor (sTfR). Increased free erythrocyte protoporphyrins (FEPs) cou... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837291 Mon, 28 Sep 2009 16:46:58 +0100 2837291 http://www.medworm.com/index.php?rid=2837290&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001000%2Fabstract%3Frss%3Dyes Anemia of inflammation (AI) is a complex multi-organ response to inflammatory disorders. Because AI can result from many infectious and non-infectious inflammatory diseases, multiple mechanisms may contribute to its pathogenesis, including iron restriction, direct erythropoietic suppression, shortened red blood cell survival, and frank hemolysis. Animal models have been helpful in the study of the mechanisms of AI and its potential treatments, but each model reflects distinct aspects of this heterogeneous syndrome. It is therefore important to study a variety of models of AI. This review focuses on the use of infectious and noninfectious mouse models of inflammation that have been shown to manifest anemia. We review many of the models reported in the literature or developed in our laborato... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837290 Mon, 28 Sep 2009 16:46:58 +0100 2837290 http://www.medworm.com/index.php?rid=2837289&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309000997%2Fabstract%3Frss%3Dyes The causes of iron deficiency vary significantly during different stages of life, and according to gender and socioeconomic circumstances. Although dietary iron is important, iron deficiency anemia (IDA) is mostly attributed to blood loss and may be the presenting clinical feature of occult bleeding from the gastrointestinal (GI) tract heralding underlying malignancy. Conventional GI diagnostic workup fails to establish the cause of iron deficiency in about one third of patients. However, abnormal iron absorption caused by hereditary iron-refractory iron deficiency anemia (IRIDA) or acquired disease is increasingly recognized as an important cause of unexplained iron deficiency. The recent availability of convenient, non-invasive screening methods to identify celiac disease, autoimmune atr... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837289 Mon, 28 Sep 2009 16:46:58 +0100 2837289 http://www.medworm.com/index.php?rid=2837288&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309001012%2Fabstract%3Frss%3Dyes Important advances in our understanding of iron metabolism have been made during the past 10 years, highlighting the mechanisms by which dysregulated iron homeostasis leads to hematologic, metabolic, and neurodegenerative diseases. In particular, the discovery of hepcidin and its fundamental role as the hormonal peptide regulating iron metabolism has delineated the organization of the complex network of proteins that regulates iron metabolism within the body. Maintenance of iron homeostasis is the consequence of tight coordination between iron absorption from the diet by enterocytes, and iron recycling by macrophages following degradation of senescent erythrocytes. Thus, any perturbation of these processes leads to a wide spectrum of diseases, ranging from iron deficiency anemia to iron ov... Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837288 Mon, 28 Sep 2009 16:46:58 +0100 2837288 http://www.medworm.com/index.php?rid=2837287&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719630900105X%2Fabstract%3Frss%3Dyes Progress in our understanding of iron metabolism over the last 10 years has been accompanied by important advances in defining the molecular mechanisms of dysregulated iron homeostasis. These advances have been relevant for a range of clinical manifestations, from states of iron deficiency to those of iron overload. (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2837287 Mon, 28 Sep 2009 16:46:57 +0100 2837287 http://www.medworm.com/index.php?rid=2490478&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309000900%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2490478 Thu, 25 Jun 2009 07:43:55 +0100 2490478 http://www.medworm.com/index.php?rid=2490477&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309000924%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2490477 Thu, 25 Jun 2009 07:43:55 +0100 2490477 http://www.medworm.com/index.php?rid=2490476&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS0037196309000912%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2490476 Thu, 25 Jun 2009 07:43:55 +0100 2490476 http://www.medworm.com/index.php?rid=2490475&cid=s_38657_19_f&fid=38657&url=http%3A%2F%2Fwww.seminhematol.org%2Farticle%2FPIIS003719630900081X%2Fabstract%3Frss%3Dyes (Source: Seminars in Hematology) Seminars in Hematology journals http://www.medworm.com/rss/comments.php?id=2490475 Thu, 25 Jun 2009 07:43:55 +0100 2490475