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The American Journal of Nursing Oct 2023
Topics: Humans; Anemia, Sickle Cell
PubMed: 37732651
DOI: 10.1097/01.NAJ.0000979024.34304.0e -
Hematology. American Society of... Dec 2023Alloimmunization against red blood cell antigens and delayed hemolytic transfusion reaction (DHTR) are major barriers to transfusion in sickle cell disease (SCD). In...
Alloimmunization against red blood cell antigens and delayed hemolytic transfusion reaction (DHTR) are major barriers to transfusion in sickle cell disease (SCD). In SCD, DHTR is a potentially life-threatening. Blood group polymorphism in SCD patients, who are of African ancestry and frequently exposed to antigens they do not carry; an inflammatory clinical state; and occasional transfusion in acute situations are risk factors for alloimmunization and DHTR. In patients at risk, the transfusion indication must be balanced against the risk of developing DHTR. However, when transfusion is absolutely necessary, protocols combining the prevention of exposure to immunogenic antigens with immunosuppressive treatments must be implemented, and patients should be carefully monitored during posttransfusion follow-up. This close monitoring makes it possible to diagnose hyperhemolysis as soon as possible; to avoid retransfusion, which can exacerbate hemolysis; and to administer specific treatments, such as anticomplement therapy, in severe cases. Finally, in patients with severe disease, hematopoietic stem cell transplantation may be indicated. However, transfusion is also required in this context, and its management is complex because these risks must be taken into account.
Topics: Humans; Transfusion Reaction; Anemia, Sickle Cell; Anemia, Hemolytic, Autoimmune; Hemolysis; Blood Transfusion; Isoantibodies
PubMed: 38066873
DOI: 10.1182/hematology.2023000499 -
Blood Nov 2023
Topics: Animals; Mice; Anemia, Sickle Cell; Vascular Diseases; Complement Activation; Pain
PubMed: 38032675
DOI: 10.1182/blood.2023022621 -
Hematology. American Society of... Dec 2023Sickle cell disease (SCD) is potentially curable after allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT after ex vivo genetic modification....
Sickle cell disease (SCD) is potentially curable after allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT after ex vivo genetic modification. Autologous HSCT with gene therapy has the potential to overcome many of the limitations of allogeneic HSCT that include the lack of suitable donors, graft-versus-host disease, the need for immune suppression, and the potential for graft rejection. Significant progress in gene therapy for SCD has been made over the past several decades, now with a growing number of clinical trials investigating various gene addition and gene editing strategies. Available results from a small number of patients, some with relatively short follow-up, are promising as a potentially curative strategy, with current efforts focused on continuing to improve the efficacy, durability, and safety of gene therapies for the cure of SCD.
Topics: Humans; Anemia, Sickle Cell; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Transplantation, Autologous; Genetic Therapy
PubMed: 38066927
DOI: 10.1182/hematology.2023000487 -
Journal of Pediatric Endocrinology &... Apr 2006
Topics: Humans; Thalassemia; Child; Male
PubMed: 38742784
DOI: 10.1515/jpem-2006-190403 -
Nature Medicine Dec 2023Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT...
Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at pre- and post-GT time points to map the somatic mutation and clonal landscape of gene-modified and unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified among gene-modified or unmodified cells; however, an increased frequency of potential driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) was observed in both genetically modified and unmodified cells, suggesting positive selection of mutant clones during GT. This work sheds light on HSC clonal dynamics and the mutational landscape after GT in SCD, highlighting the enhanced fitness of some HSCs harboring pre-existing driver mutations. Future studies should define the long-term fate of mutant clones, including any contribution to expansions associated with myeloid neoplasms.
Topics: Humans; Hematopoiesis; Phylogeny; Mutation; Hematopoietic Stem Cells; Clone Cells; Anemia, Sickle Cell; Genetic Therapy; Neoplasms
PubMed: 37973947
DOI: 10.1038/s41591-023-02636-6 -
Journal of General Internal Medicine Nov 2023Sickle cell disease (SCD) is the most common monogenetic condition in the United States (US) and one that has been subjected to a history of negative bias. Since SCD was...
Sickle cell disease (SCD) is the most common monogenetic condition in the United States (US) and one that has been subjected to a history of negative bias. Since SCD was first described approximately 120 years ago, the medical establishment has, directly and indirectly, harmed patients by reinforcing biases and assumptions about the disease. Furthermore, negative biases and stigmas have been levied upon patients with SCD by healthcare providers and society, researchers, and legislators. This article will explore the historical context of SCD in the US; discuss specific issues in care that lead to biases, social and self-stigma, inequities in access to care, and research funding; and highlight interventions over recent years that address racial biases and stigma.
Topics: Humans; United States; Social Stigma; Racism; Anemia, Sickle Cell; Health Personnel; Surveys and Questionnaires
PubMed: 37698721
DOI: 10.1007/s11606-023-08392-0 -
Indian Journal of Pediatrics Dec 2023Thalassemia is one of the most common hemoglobinopathies affecting a large number of people in India and other countries of South-East Asia. For patients with most... (Review)
Review
Thalassemia is one of the most common hemoglobinopathies affecting a large number of people in India and other countries of South-East Asia. For patients with most severe form of the disease- Transfusion Dependent Thalassemia (TDT), stem cell transplantation or gene therapy are only curative treatment which are not available to most of the patients because of lack of experts, financial constraints and lack of suitable donors. In such situations, most cases are managed with regular blood transfusion and iron chelation therapy. With this treatment, over the years, survival of the patients has improved and 20-40% cases are entering into adulthood. In the absence of structured transition of care programs, currently most adult TDT patients are being managed by pediatricians. This article highlights the need for transition of care for TDT patients, barriers to transition and how to overcome the barriers and process of transition of care to adult care team. The importance of empowering the patients in self-management of the disease and educating the adult care team to achieve the desired outcome of transition program is highlighted.
Topics: Adult; Humans; beta-Thalassemia; Chelation Therapy; Hematopoietic Stem Cell Transplantation; Patient Transfer; Stem Cell Transplantation; Thalassemia; Transition to Adult Care
PubMed: 37133752
DOI: 10.1007/s12098-023-04595-9 -
Clinical Biochemistry Aug 2023Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000...
BACKGROUND
Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000 disorders of Hb synthesis and/or structure have been identified and characterized, with phenotypes ranging from having severe clinical manifestations to clinically silent. Various analytical methods are used to phenotypically detect Hb variants. However, molecular genetic analysis is a more definitive method for Hb variant identification.
CASE REPORT
Here, we report a case of a 23-month-old male with results from capillary electrophoresis, gel electrophoresis (acid and alkaline), and high-performance liquid chromatography most consistent with HbS trait. Specifically, capillary electrophoresis showed slightly elevated HbF and HbA2, HbA of 39.4% and HbS of 48.5%. The HbS percentage was consistently higher than expected (typically 30-40%) for HbS trait with no concurrent thalassemic indices. The patient has not experienced any clinical complications due to the hemoglobinopathy and he is thriving.
CONCLUSION
Molecular genetic analysis revealed the presence of compound heterozygosity for HbS and Hb Olupona. Hb Olupona is an extremely rare beta-chain variant that appears as HbA on all three common methods used for phenotypic Hb analysis. When the fractional concentration of Hb variants is unusual, more definitive methods should be used, such as mass spectrometry or molecular genetic testing. In this case, incorrectly reporting this result as HbS trait is unlikely to have a significant clinical impact, as current evidence suggests Hb Olupona is not a clinically significant variant.
Topics: Male; Humans; Hemoglobins, Abnormal; Hemoglobinopathies; Thalassemia; Hemoglobin A2; Electrophoresis, Capillary
PubMed: 37236295
DOI: 10.1016/j.clinbiochem.2023.110589 -
Annals of the New York Academy of... Nov 2023Thalassemia management has undergone significant development with the advancement in iron chelation therapy, which has led to a prolonged life expectancy. This has been... (Review)
Review
Thalassemia management has undergone significant development with the advancement in iron chelation therapy, which has led to a prolonged life expectancy. This has been accompanied by the emergence of several new morbidities and chronic diseases, including cancer. Over the years, multiple cases of solid and hematologic malignancies in thalassemia patients have been reported in the literature, with no clear mechanism for the development of cancer in these patients despite a number of potential mechanisms. However, the results of many studies have been contradictory regarding the risk of development of malignancies in thalassemia. The present review aims to discuss the available data on cancer and thalassemia in the literature, with the latest updates regarding possible malignancy development mechanisms, risks, and the most commonly reported types.
Topics: Humans; Blood Transfusion; Thalassemia; Neoplasms; Hematologic Neoplasms; Iron Chelating Agents; Iron Overload
PubMed: 37676814
DOI: 10.1111/nyas.15061