[Show abstract][Hide abstract] ABSTRACT: The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
[Show abstract][Hide abstract] ABSTRACT: Pearson syndrome (PS) is a very rare and often fatal multisystemic mitochondrial disorder involving the liver, kidney, pancreas, and hematopoietic and central nervous system. It is characterized principally by a transfusion-dependent anemia that usually improves over time, a tendency to develop severe infections, and a high mortality rate. We describe a group of 11 PS patients diagnosed in Italy in the period 1993-2014. The analysis of this reasonably sized cohort of patients contributes to the clinical profile of the disease and highlights a rough incidence of 1 case/million newborns. Furthermore, it seems that some biochemical parameters like increased serum alanine and urinary fumaric acid can help to address an early diagnosis.
[Show abstract][Hide abstract] ABSTRACT: Fanconi anemia (FA) is a rare bone marrow failure disorder characterized by clinical and genetic heterogeneity with at least 17 genes involved, which make molecular diagnosis complex and time-consuming. Since next-generation sequencing technologies could greatly improve the genetic testing in FA, we sequenced DNA samples with known and unknown mutant alleles using the Ion PGM™ system (IPGM). The molecular target of 74.2 kb in size covered 96% of the FA-coding exons and their flanking regions. Quality control testing revealed high coverage. Comparing the IPGM and Sanger sequencing output of FANCA, FANCC, and FANCG we found no false-positive and a few false-negative variants, which led to high sensitivity (95.58%) and specificity (100%) at least for these two most frequently mutated genes. The analysis also identified novel mutant alleles, including those in rare complementation groups FANCF and FANCL. Moreover, quantitative evaluation allowed us to characterize large intragenic deletions of FANCA and FANCD2, suggesting that IPGM is suitable for identification of not only point mutations but also copy number variations.
[Show abstract][Hide abstract] ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of treatment-related mortality and may be associated with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks. IBMFS are rare, whereas case reports and small series in the literature illustrate highly heterogeneous practices in terms of indications for HSCT, timing, stem cell source and conditioning regimens. A consensus meeting was therefore held in Vienna in September 2012 on behalf of the European Group for Blood and Marrow Transplantation to discuss HSCT in the setting of IBMFS. This report summarizes the recommendations from this expert panel, including indications for HSCT, timing, stem cell source and conditioning regimen.Bone Marrow Transplantation advance online publication, 8 June 2015; doi:10.1038/bmt.2015.117.
Full-text · Article · Jun 2015 · Bone marrow transplantation
[Show abstract][Hide abstract] ABSTRACT: Aplastic anemia is a rare disorder characterized by suppression of bone marrow function resulting in progressive pancytopenia. A trigger-related abnormal T cell response facilitated by some genetic predisposition has been postulated as the pathogenetic mechanism leading to the overproduction of bone marrow-inhibiting cytokines. Immuno-mediated pathogenesis is confirmed by the response to immunosuppressive treatment (IST) (cyclosporin A+ATG), which represents the first-choice therapy for patients <40 years when a matched sibling donor (MSD) is not available for transplant. MSD hematopoietic stem cell transplantation (HSCT) is associated with cure in ~90 % of patients. IST up-front provides an overall survival (OS) rate of above 90 %, but a response rate of about 60 %. Front-line matched unrelated donor (MUD) appears to be a viable option in children with similar OS and event-free survival to that in MSD HSCT. MUD HSCT post-IST failure proved to be a very good rescue strategy. Haploidentical donors/cord blood transplants or alternative immunosuppressive therapies, such as alemtuzumab, may represent valid tools for resistant/relapsing cases. New promising strategies, such as eltrombopag, are now under investigation. Patients should be offered an accurate diagnostic work-up in order to rule out other underlying disorders, primarily constitutional marrow failures, which may require different approaches.
Full-text · Article · Apr 2015 · International journal of hematology
[Show abstract][Hide abstract] ABSTRACT: This is the sixth special report that the European Society for Blood and Marrow Transplantation regularly publishes on the current practice and indications for haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred in the field of haematopoietic SCT over the last years. Cord blood units as well as haploidentical donors have been increasingly used as stem cell sources for allo-SCT, thus, augmenting the possibility of finding a suitable donor for a patient. Continuous refinement of conditioning strategies has also expanded not only the number of potential indications but also has permitted consideration of older patients or those with co-morbidity for a transplant. There is accumulating evidence of the role of haematopoietic SCT in non-haematological disorders such as autoimmune diseases. On the other hand, the advent of new drugs and very effective targeted therapy has challenged the role of SCT in some instances or at least, modified its position in the treatment armamentarium of a given patient. An updated report with revised tables and operating definitions is presented.Bone Marrow Transplantation advance online publication, 23 March 2015; doi:10.1038/bmt.2015.6.
Full-text · Article · Mar 2015 · Bone marrow transplantation
[Show abstract][Hide abstract] ABSTRACT: This case report indicates the usefulness of voriconazole for the treatment of central nervous system (CNS) aspergillosis, also in paediatrics. However, it also confirms the need for therapeutic drug monitoring (TDM), especially in younger children that may require very high dosages in order to achieve plasma and cerebrospinal fluid (CSF) therapeutic concentrations.
No preview · Article · Mar 2015 · Journal of chemotherapy (Florence, Italy)