Outcomes Following Gene Therapy in Patients With Severe Wiskott-Aldrich Syndrome

Abina, Salima Hacein-Bey; Gaspar, H. Bobby; Blondeau, Johanna; Caccavelli, Laure; Charrier, Sabine; Buckland, Karen F.; Pïcard, Capucine; Six, Emmanuelle; Himoudi, Nourredine; Gilmour, Kimberly; McNicol, Anne-Marie; Hara, Havinder; Xu‐Bayford, Jinhua; Rivat, Christine; Touzot, Fabien; Mavilio, Fulvio; Lim, Annick; Tréluyer, Jean‐Marc; Héritier, Sébastien; Lefrère, François; Magalon, Jérémy; Pengue-Koyi, Isabelle; Honnet, Géraldine; Blanche, Stéphane; Sherman, Eric A.; Male, Frances; Berry, Charles C.; Malani, Nirav; Bushman, Frederic D.; Fischer, Alain; Thrasher, Adrian J.; Galy, Anne; Cavazzana, Marina

doi:10.1001/jama.2015.3253

Cited by 338 publications

(298 citation statements)

References 42 publications

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“…Thrombocytopenias caused by variants in RUNX1, ETV6, and ANKRD26 9,68,69 are associated with increased risk of myeloid malignancy, whereas for WAS and amegakaryocytic thrombocytopenia caused by MPL variants, treatment by allogeneic hematopoietic stem cell transplant or gene therapy may require consideration. [70][71][72] Moreover, genetic counseling can be provided if the diagnosis is confirmed at the DNA level. Current guidelines favor a tiered approach to IPD diagnosis.…”

Section: Current Approaches To Diagnosismentioning

confidence: 99%

Inherited platelet disorders: toward DNA-based diagnosis

Lentaigne

Freson

Laffan

et al. 2016

Blood

121

101

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Variations in platelet number, volume, and function are largely genetically controlled, and many loci associated with platelet traits have been identified by genome-wide association studies (GWASs).1 The genome also contains a large number of rare variants, of which a tiny fraction underlies the inherited diseases of humans. Research over the last 3 decades has led to the discovery of 51 genes harboring variants responsible for inherited platelet disorders (IPDs). However, the majority of patients with an IPD still do not receive a molecular diagnosis. Alongside the scientific interest, molecular or genetic diagnosis is important for patients. There is increasing recognition that a number of IPDs are associated with severe pathologies, including an increased risk of malignancy, and a definitive diagnosis can inform prognosis and care. In this review, we give an overview of these disorders grouped according to their effect on platelet biology and their clinical characteristics. We also discuss the challenge of identifying candidate genes and causal variants therein, how IPDs have been historically diagnosed, and how this is changing with the introduction of high-throughput sequencing. Finally, we describe how integration of large genomic, epigenomic, and phenotypic datasets, including whole genome sequencing data, GWASs, epigenomic profiling, protein–protein interaction networks, and standardized clinical phenotype coding, will drive the discovery of novel mechanisms of disease in the near future to improve patient diagnosis and management.

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Section: Current Approaches To Diagnosismentioning

confidence: 99%

Inherited platelet disorders: toward DNA-based diagnosis

Lentaigne

Freson

Laffan

et al. 2016

Blood

121

101

View full text Add to dashboard Cite

show abstract

“…For these patients, diagnosis can be delayed or difficult and the natural history of exceptionally rare underlying diseases is often unclear. In several PIDs, controversy surrounding optimum timing of Allo-HSCT remains, due to rarity of disease, lack of experience, emerging gene therapies, [14][15][16][17] and infrequent published outcome data due to the very low numbers in any 1 center.…”

Section: Introductionmentioning

confidence: 99%

Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency

Fox

Chakraverty

Burns

et al. 2018

Blood

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“…All six surviving patients exhibited high-level, stable engraftment of functionally corrected lymphoid cells. The degree of myeloid cell engraftment and of platelet reconstitution correlated with the dose of gene-corrected cells administered [53]. No evidence of vector-related toxicity was observed either clinically or by molecular analysis in either of these clinical trials using SIN lentiviral vectors, although long-term follow-up is still required [52,53].…”

Section: Other Ex Vivo Gene Therapies For Hematological and Non-hematmentioning

confidence: 93%

Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world

Tani

2016

Int J Hematol

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Outcomes Following Gene Therapy in Patients With Severe Wiskott-Aldrich Syndrome

Cited by 338 publications

References 42 publications

Inherited platelet disorders: toward DNA-based diagnosis

Inherited platelet disorders: toward DNA-based diagnosis

Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency

Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world

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