Hemoglobin disorders: lentiviral gene therapy in the starting blocks to enter clinical practice

Sii-Felice, Karine; Giorgi, Marie-Laurence; Leboulch, Philippe; Payen, Emmanuel

doi:10.1016/j.exphem.2018.05.004

Cited by 35 publications

(35 citation statements)

References 217 publications

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“…These modified HSCs are then introduced into the patient following myeloablative conditioning [13,14]. Gene addition therapy using autologous HSCs may offer an alternative to allo-HSCT for patients with TDT who do not have a suitably matched related donor [15,16]. Gene addition therapy using autologous HSCs would allow these patients to avoid the risk of GvHD and would not require immunosuppression to prevent graft rejection [15,17].…”

Section: Introductionmentioning

confidence: 99%

Health state utilities associated with treatment for transfusion-dependent β-thalassemia

et al. 2019

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Objectives Transfusion-dependent β-thalassemia (TDT) is a genetic disease that affects production of red blood cells. Conventional treatment involves regular red blood cell transfusions and iron chelation, which has a substantial impact on quality of life. While potentially curative, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with risk of complications, including graft-versus-host disease (GvHD). Gene addition therapy, a novel treatment approach, involves autologous transplantation of the patient's own genetically modified hematopoietic stem cells. The purpose of this study was to estimate utilities associated with treatment approaches for TDT. Methods General population respondents in England valued eight health state vignettes (developed with clinician, patient, and parent input) in time trade-off interviews. Results A total of 207 participants completed interviews (49.8% female; mean age = 43.2 years). Mean (SD) utilities for the pre-transplant health states were 0.73 (0.25) with oral chelation and 0.63 (0.32) with subcutaneous chelation. Mean utilities for the transplant year were 0.62 (0.35) for gene addition therapy, 0.47 (0.39) for allo-HSCT, and 0.39 (0.39) for allo-HSCT with acute GvHD. Post-transplant utilities were 0.93 (0.15) for transfusion independent, 0.75 (0.25) for 60% transfusion reduction, and 0.51 (0.38) for chronic GvHD. Acute and chronic GvHD were associated with significant disutility (acute = − 0.09, p < 0.0001; chronic = − 0.42, p < 0.0001). Conclusions Utilities followed expected patterns, with logical differences between treatment options for TDT and substantially greater utility for transfusion independence than for ongoing treatment involving transfusion and chelation. These utilities may be useful in cost-utility models estimating the value of treatments for TDT.

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Section: Introductionmentioning

confidence: 99%

Health state utilities associated with treatment for transfusion-dependent β-thalassemia

et al. 2019

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“…The adverse events observed were transplant related and not attributed to lentiviral gene therapy itself [102]. Numerous phase I-II clinical trials are ongoing and, in the future, patients lacking an HLA-identical donor will certainly be eligible and benefit from gene therapy [103,104].…”

Section: Gene Therapymentioning

confidence: 98%

Present and Future Strategies with Curative Intent for Hereditary Hemoglobinopathies

Oliveira¹,

Saraiva²,

Costa³

et al. 2019

obm transplant

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Nowadays, hematopoietic stem cell transplantation (HSCT) is a common procedure in hematology units within reference centers, mainly for the treatment of hematological malignancies such as multiple myeloma, lymphoma, and acute leukemia. Nevertheless, HSCT has much wider applications, namely in autoimmune diseases, congenital metabolic defects, and hemoglobinopathies. Thalassemia major and sickle cell disease make up the most frequent hereditary hemoglobinopathies worldwide. Despite advances on the prevention and treatment of complications related to these diseases, the only curative approach available resides in allogeneic HSCT. The main challenges of this treatment remain focused on the toxicity of pre-transplant conditioning regimens and short-term transplant related complications like graft-versus-host disease, infections, and disease recurrence. Thus, it is crucial to establish a balance between the risk vs benefit of HSCT for each patient and follow the available guidelines for both diseases. Recently, gene therapy has become a real alternative to allogeneic HSCT. Recent advances in molecular biology methods have provided more accurate and reliable gene editing techniques such as the CRISP/CAS9 system. The long-term outcome of gene manipulation procedures remains uncertain, especially in

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“…Dadas las limitaciones en este tratamiento de trasplante, la terapia génica mediante una modificación ex vivo de células madre hematopoyéticas (CMH) seguida de un injerto autólogo, es una nueva modalidad terapéutica atractiva [37]. Esta nueva alternativa es especialmente novedosa, sobretodo para pacientes que no tienen un donante compatible emparejado, en los cuales la terapia génica con globina ofrece la promesa de un trasplante de células madre autólogo curativo sin incurrir en los riesgos de la enfermedad de injerto contra huésped [38].…”

Section: Tratamientounclassified

Beta-Talasemia: Un mundo de complicaciones con nuevas alternativas de tratamiento.

Alzate

2019

archmed

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Introducción: β-talasemia, es causada por mutaciones en el gen de la globina HBB, que codifica la subunidad β de la HbA. La enfermedad es conocida por ser altamente prevalente en el área que se extiende desde África subsahariana, a través de la región mediterránea y Medio Oriente. En Colombia, se han reportado varios estudios independientes de hemoglobinopatías en ciudades como Cartagena, Buenaventura, Cali, San Andrés y Providencia debido a su gran población afrodescendiente sobre la cual las Talasemias y otras hemoglobinopatías tienen incidencia directa. Objetivo: recolectar datos acerca de las características clínicas, complicaciones y clasificaciones de β-talasemia con el fin de brindar una fuente de información que permita realizar un diagnóstico eficaz y en consecuencia un tratamiento que busque llegar a la curación completa de los pacientes que sufren esta condición, con el mínimo de complicaciones para los mismos. Conclusión: la β-Talasemia es una hemoglobinopatía estructural que tiene un porcentaje de prevalencia e incidencia importante en el mundo. En Colombia no se tiene claro cuál es la epidemiología real para esta condición puesto que no se han realizado estudios que abarquen una muestra adecuada y significativa. Esta enfermedad genera múltiples complicaciones en diferentes órganos, que no solo están asociadas al desarrollo de la enfermedad, sino también a la terapia de trasfusión a largo plazo. Por esta razón, los nuevos tratamientos están encaminas a lograr en un futuro la curación completa, reduciendo al máximo las complicaciones.

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Hemoglobin disorders: lentiviral gene therapy in the starting blocks to enter clinical practice

Cited by 35 publications

References 217 publications

Health state utilities associated with treatment for transfusion-dependent β-thalassemia

Health state utilities associated with treatment for transfusion-dependent β-thalassemia

Present and Future Strategies with Curative Intent for Hereditary Hemoglobinopathies

Beta-Talasemia: Un mundo de complicaciones con nuevas alternativas de tratamiento.

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