Applicability of and potential barriers preventing allogeneic stem cell transplant in sickle cell patients treated outside a sickle cell program

American Journal of Hematology, EarlyView.
Source: American Journal of Hematology - Category: Hematology Source Type: research

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Abstract Sickle cell disease (SCD) is caused by a mutation of the b-globin gene(21) that triggers the polymerization of deoxygenated sickle hemoglobin (HbS). Approximately 100,000 SCD patients in the U.S. and millions worldwide(53) suffer from chronic hemolytic anemia, painful crises, multisystem organ damage, and reduced life expectancy(60, 70). Hematopoietic stem cell (HSC) transplantation can be curative, but the majority of patients do not have a suitable donor (80). Advanced gene editing technologies also offer the possibility of a cure (16, 34), but the likelihood that these strategies can be mobilized to tr...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research
CONCLUSIONS: The results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients. PMID: 30001893 [PubMed - as supplied by publisher]
Source: Medicina Clinica - Category: General Medicine Tags: Med Clin (Barc) Source Type: research
Publication date: May 2018Source: Blood Cells, Molecules, and Diseases, Volume 70Author(s): Maria Rosa Lidonnici, Giuliana FerrariAbstractGene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with an integrating lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Studies and safety works demonstrated the potential therapeutic efficacy and safety of this approach, providing the rationale for clinical translation. The outcomes of early clinical trials, although showing promising results, hav...
Source: Blood Cells, Molecules, and Diseases - Category: Hematology Source Type: research
Publication date: Available online 30 May 2018Source: CytotherapyAuthor(s): Selami Demirci, Naoya Uchida, John F. TisdaleAbstractSickle cell disease (SCD) is one of the most common life-threatening monogenic diseases affecting millions of people worldwide. Allogenic hematopietic stem cell transplantation is the only known cure for the disease with high success rates, but the limited availability of matched sibling donors and the high risk of transplantation-related side effects force the scientific community to envision additional therapies. Ex vivo gene therapy through globin gene addition has been investigated extensivel...
Source: Cytotherapy - Category: Cytology Source Type: research
The recent article from Nickel and Kamani1 raised very important ethical points related to the use of Preimplantation Genetic Diagnosis (PGD) by parents of children with sickle cell disease (SCD), as a method to avoid having another child with the disease and create a matched related sibling that could allow the cure of their affected child by means of a hematopoietic stem cell transplant (HSCT).2 The authors explain how it has become an acceptable procedure in our society, for these parents, to use PGD techniques to create multiple embryos through in-vitro fertilization (IVF), select one among those who are both healthy a...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: Letter Source Type: research
Publication date: May 2018Source: Blood Cells, Molecules, and Diseases, Volume 70Author(s): Maria Rosa Lidonnici, Giuliana FerrariAbstractGene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with an integrating lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Studies and safety works demonstrated the potential therapeutic efficacy and safety of this approach, providing the rationale for clinical translation. The outcomes of early clinical trials, although showing promising results, hav...
Source: Blood Cells, Molecules, and Diseases - Category: Hematology Source Type: research
Publication date: Available online 30 May 2018Source: CytotherapyAuthor(s): Selami Demirci, Naoya Uchida, John F. TisdaleAbstractSickle cell disease (SCD) is one of the most common life-threatening monogenic diseases affecting millions of people worldwide. Allogenic hematopietic stem cell transplantation is the only known cure for the disease with high success rates, but the limited availability of matched sibling donors and the high risk of transplantation-related side effects force the scientific community to envision additional therapies. Ex vivo gene therapy through globin gene addition has been investigated extensivel...
Source: Cytotherapy - Category: Cytology Source Type: research
Conclusion: Busulfan, cyclophosphamide, and ATG-based conditioning for HSCT of TM and SCD patients did not result in graft failure, although modifications may be required to reduce VOD incidence. Further changes to donor type and cell source prioritization are necessary to minimize TRM and morbidity caused by GVHD. PMID: 29963521 [PubMed]
Source: Blood Research - Category: Hematology Tags: Blood Res Source Type: research
Disorders involving β-globin gene mutations, primarily β-thalassemia and sickle cell disease, represent a major target for hematopoietic stem/progenitor cell (HSPC) gene therapy. This includes CRISPR/Cas9-mediated genome editing approaches in adult CD34+ cells aimed toward the reactivation of fetal -globin expression in red blood cells. Because models involving erythroid differentiation of CD34+ cells have limitations in assessing -globin reactivation, we focused on human β-globin locus-transgenic (β-YAC) mice. We used a helper-dependent human CD46-targeting adenovirus vector expressing CRISPR/Cas9 (HDA...
Source: Blood - Category: Hematology Authors: Tags: Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis, Gene Therapy Source Type: research
Authors: Leonard A, Tisdale J Abstract INTRODUCTION: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide, and is a life limiting disease with limited therapeutic options to reduce disease severity. Despite being a monogenic disorder, the clinical phenotypes of SCD are variable, with few reliable predictors of disease severity easily identifying patients where the benefits of curative therapy outweigh the risks. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option, though significant advances in gene therapy raise the promise for additional curative meth...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
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