Seminars in Hematology RSS feed: Current Issue. Seminars in Hematology is a topical journal that focuses on subjects of current importance in clinical hematology and related fields. The journal is devoted to making the present status of such topics and the results of new investigations readily available to the practicing physician. Seminars in Hematology is of special interest to hematologists, oncologists, internal medicine specialists, blood bankers and specialists in thrombosis and hemostasis.http://www.seminhematol.org/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. Seminars in Hematology0037-1963471January 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.seminhematol.org/article/PIIS0037196309001462/abstract?rss=yesMasthead10.1053/S0037-1963(09)00146-2Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-7IFCIFChttp://www.seminhematol.org/article/PIIS0037196309001437/abstract?rss=yesOctober 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.Umbilical Cord Transplantation: State of the Art 2010John E. Wagner10.1053/j.seminhematol.2009.11.001Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-712http://www.seminhematol.org/article/PIIS0037196309001425/abstract?rss=yesIn 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 into novel therapeutic approaches. This chapter briefly summarizes the highpoints of the history of UCBT with speculations as to what the next generation of research promises to discover.Umbilical Cord Blood Transplantation: The First 20 YearsJohn E. Wagner, Eliane Gluckman10.1053/j.seminhematol.2009.10.011Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-7312http://www.seminhematol.org/article/PIIS0037196309001346/abstract?rss=yesThe 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.Unrelated Umbilical Cord Blood Unit SelectionAndromachi Scaradavou, National Cord Blood Program, New York Blood Center10.1053/j.seminhematol.2009.10.003Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-71321http://www.seminhematol.org/article/PIIS0037196309001401/abstract?rss=yesThis 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 infusion (DLI) are also discussed.Unrelated Umbilical Cord Blood Transplantation and Immune ReconstitutionPaul Szabolcs, Mitchell S. Cairo10.1053/j.seminhematol.2009.10.009Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-72236http://www.seminhematol.org/article/PIIS0037196309001358/abstract?rss=yesAllogeneic 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.Transplant Outcomes in Bone Marrow Failure Syndromes and HemoglobinopathiesMargaret L. MacMillan, Mark C. Walters, Eliane Gluckman10.1053/j.seminhematol.2009.10.004Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-73745http://www.seminhematol.org/article/PIIS0037196309001383/abstract?rss=yesUmbilical 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 advantage after transplantation of matched unrelated bone marrow compared to UCB, while others report similar leukemia-free survival. Work is in progress to improve hematopoietic recovery and lower early transplant-related deaths, the two major limitations to a successful outcome after UCB transplant. The importance of HLA-matching and cell dose on outcomes after UCB transplantation support the need for an even greater investment in public cord blood banks. Simultaneously searching of accredited cord blood banks and bone marrow donor registries for patients without an HLA-matched sibling thought to benefit from hematopoietic stem cell transplantation (HSCT) is encouraged.Transplant Outcomes in Acute Leukemia (I)Mary Eapen, John E. Wagner10.1053/j.seminhematol.2009.10.007Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-74650http://www.seminhematol.org/article/PIIS003719630900136X/abstract?rss=yesCurrently, 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 regimens, and developments on immunotherapy have focused attention on this option. Therefore, any physician has to carefully evaluate, for each patient in need of an allograft, all of the possible alternatives in order to choose the best HSC donor, taking into account type of disease to be transplanted, urgency of transplantation, donor characteristics, and center experience. This review evaluates the current status of haploidentical HSCT in acute leukemia, its advantages and remaining limitations compared to other stem cell sources, and how these data may be used in the development of donor selection algorithms.Transplant Outcomes in Acute Leukemia (II)Rachael Hough, Vanderson Rocha10.1053/j.seminhematol.2009.10.005Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-75158http://www.seminhematol.org/article/PIIS0037196309001395/abstract?rss=yesThe 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 organs, improve neurocognitive function and quality of life, and prolong survival, particularly when performed early in the course of the disease. Bone marrow has been the graft source in the past. However, in the last 5 years many patients have been treated with unrelated donor (URD) umbilical cord blood transplant (UCBT), allowing rapid and increased access to transplantation with favorable outcomes. This review describes published and our institutional clinical experiences, discusses the current status of the field, and provides therapy guidelines for patients with MPS.Transplant Outcomes in MucopolysaccharidosesVinod K. Prasad, Joanne Kurtzberg10.1053/j.seminhematol.2009.10.008Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-75969http://www.seminhematol.org/article/PIIS0037196309001371/abstract?rss=yesHematopoietic 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 approximately 40% of cases a progressive, inflammatory condition develops in the CNS. Early in the course of the disease, allogeneic transplantation can arrest the disease process in cerebral adrenoleukodystrophy, while more advanced patients do poorly. In many of these cases, the utilization of cord blood grafts allows expedient transplantation, which can be critical in achieving optimal outcomes.Transplant Outcomes in LeukodystrophiesPaul J. Orchard, Jakub Tolar10.1053/j.seminhematol.2009.10.006Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-77078http://www.seminhematol.org/article/PIIS0037196309001322/abstract?rss=yesPrimary 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 the use of UCB transplantation for PID is a viable option and may be advantageous in many situations.Transplant Outcomes for Primary Immunodeficiency DiseaseAngela R. Smith, Thomas G. Gross, K. Scott Baker10.1053/j.seminhematol.2009.10.001Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-77985http://www.seminhematol.org/article/PIIS0037196309001413/abstract?rss=yesThe 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.Extending Cord Blood Transplant to Adults: Dealing With Problems and Results OverallClaudio G. Brunstein, Mary J. Laughlin10.1053/j.seminhematol.2009.10.010Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-78696http://www.seminhematol.org/article/PIIS0037196309001334/abstract?rss=yesThe 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.Umbilical Cord Transplantation: EpilogueHal E. Broxmeyer10.1053/j.seminhematol.2009.10.002Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-797103http://www.seminhematol.org/article/PIIS0037196309001474/abstract?rss=yesTable of Contents10.1053/S0037-1963(09)00147-4Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-7FrontmatterA5A6http://www.seminhematol.org/article/PIIS0037196309001486/abstract?rss=yesPrevious Issues10.1053/S0037-1963(09)00148-6Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-7FrontmatterA7A7http://www.seminhematol.org/article/PIIS0037196309001498/abstract?rss=yesFuture Issues and Recent Issues10.1053/S0037-1963(09)00149-8Seminars in Hematology 47, 1 (2010)2010-01-01Seminars in Hematology2010-01-01471S0037-1963(09)X0007-7FrontmatterA8A8