1,721,017 research outputs found
Transplantation for thalassemia major: Alternative donors
No full textPurpose of review Lack of a human leukocyte antigen (HLA)-matched family donor is a major obstacle limiting the use of allogeneic hematopoietic stem cell transplantation (HSCT) to cure thalassemia major. Use of alternative donors, if found well tolerated enough, may be a viable option for transplantation in this setting, allowing to expand the number of patients treatable by HSCT. This review will provide an overview of alternative HSCT approaches in thalassemia major. Recent findings With the introduction of high-resolution molecular HLA-typing techniques, the outcome of matched unrelated donor HSCT recipients has become comparable with that of patients given matched family donor HSCT. On the contrary, the use of unrelated cord blood transplantation has been limited by the risk of graft failure and slow hematopoietic recovery, although novel techniques of ex vivo graft manipulation are emerging as promising strategies for overcoming these obstacles. Although experience with haploidentical HSCT in thalassemia major is still limited, currently explored platforms hold the potential to extend the access to HSCT to thalassemia major patients lacking an HLA-matched either related or unrelated donor. Summary The significant advances achieved in transplantation techniques, both in the matched unrelated and in the haploidentical setting, are expected to significantly broaden the applicability of HSCT to patients with thalassemia major
Novel approaches to diagnosis and treatment of Juvenile Myelomonocytic Leukemia
No full textIntroduction: Juvenile myelomonocytic leukemia (JMML) is a clonal hematopoietic disorder of infancy/early childhood, resulting from oncogenic mutations in genes involved in the Ras pathway. As JMML often exhibits an aggressive course, the timing of diagnosis and treatment is critical to outcome. Areas covered: This review summarizes current approaches to diagnosis and treatment of JMML, highlighting most recent insights into genetic and epigenetic mechanisms underlying the disease, and providing an overview of novel potential therapeutic strategies. Expert commentary: At present, allogeneic HSCT remains the only potentially effective therapy, being able to cure more than 50% of patients, relapse representing the main cause of treatment failure. Prompt HSCT is recommended for all children with NF1, somatic PTPN11 and KRAS mutations, and for most children with somatic NRAS mutations. Conversely, a ‘watch and wait’ strategy should be adopted in children with germline CBL mutations, specific somatic NRAS mutation, and in Noonan syndrome patients, since spontaneous resolution has been reported to occur. Novel drugs targeting relevant nodes of JMML leukemogenesis have been explored in pre-HSCT window or at relapse. The use of 5-azacytidine, a DNA-hypomethylating agent reported to induce hematologic and molecular remission in some JMML children, is currently being investigated in clinical trials
Eltrombopag for treatment of thrombocytopenia-associated disorders
No full textIntroduction: Eltrombopag is an orally bioavailable, non-peptide thrombopoietin receptor agonist capable of stimulating platelet production through the differentiation of CD34+ hematopoietic progenitor cells into committed CD41+ megakaryocyte precursors and proliferation of megakaryocyte progenitor cells.Areas covered: This drug has been tested in several clinical trials in adult patients with chronic immune thrombocytopenia (ITP), demonstrating the ability of the drug to reduce the burden of thrombocytopenia and its associated side effects. Two multicenter trials on eltrombopag in chronic ITP of childhood have been recently completed, showing that the drug is effective also in pediatric patients. Recent studies have suggested a potential role of eltrombopag in the treatment of thrombocytopenia associated with hepatitis-C virus infection. These studies have documented that adjunct treatment with eltrombopag can help avoid either dose reductions or withdrawal of pegylated interferon due to development of thrombocytopenia. Eltrombopag has shown efficacy also in patients with acquired severe aplastic anemia and myelodysplastic syndromes.Expert opinion: Eltrombopag plays an important therapeutic role in many different conditions characterized by persistent thrombocytopenia. A more comprehensive definition of both long-term safety and benefits deriving from the use of eltrombopag will be obtained through prolonged observation of patients already enrolled in the different studies conducted so far and from future prospective controlled trials
Endocrine and gastroenterological diseases: A frequent union? [Patologie endocrine e gastroenterologiche: Un'unione frequente?]
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Hematopoietic Stem Cell Transplantation in Thalassemia
No full textAlthough recent advances in gene therapy are expected to increase the chance of disease cure in thalassemia major, at present hematopoietic stem cell transplantation (HSCT) remains the only consolidated curative approach for this disorder. The widest experience has been obtained in the HLA-matched family donor (MFD) setting, with probabilities of overall and thalassemia-free survival exceeding 90% and 85%, respectively. As for most patients a suitable MFD is not available, alternative donors (HLA-matched unrelated donor, unrelated cord blood, HLA-haploidentical relative) have been increasingly explored, translating into the expansion of the number of patients treatable with HSCT
Nuova mutazione del gene MLL2 in un caso affetto da Sindrome di Kabuki con espressione clinica tardiva
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
T cell immunotherapy for immune reconstitution and GVHD prevention after allogeneic hematopoietic stem cell transplantation
No full textMany different studies have demonstrated that early recovery of the adaptive immune system after allogeneic hematopoietic stem cell transplantation (HSCT) is predominantly sustained by peripheral expansion of donor-derived, mature lymphocytes transferred with the graft. Different approaches based on the infusion of donor T cells after HSCT have been developed mainly to accelerate immune recovery and to treat/prevent (a) malignancy recurrence, (b) life-threatening infections, and (c) immune-mediated disorders, such as graft-versus-host disease (GVHD). For many years, donor lymphocyte infusion (DLI) has been a widely used approach to prevent and to treat leukemia recurrence, to convert mixed chimerism into complete donor chimerism, and to accelerate immune reconstitution of patients after HSCT. More sophisticated strategies of adoptive infusion of T cell lines/clones capable of mediating a graft-versus-leukemia (GVL) response, while avoiding GVHD occurrence, or specific for the most life-threatening pathogens (e.g., cytomegalovirus, Epstein-Barr virus, and adenovirus) have been envisaged and successfully tested in pilot trials in the early post-transplantation period. Also, ex vivo expanded regulatory T (Treg) cells have been shown to be beneficial for preventing GVHD post-HSCT. In this review, we will focus on DLI as well as more complex cellular therapies that require extensive cell manipulation
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