Base editing of HBG1 and HBG2 promoters for sickle cell disease (Registro nro. 22925)

000 -Cabecera
Campo de control interno 03457nam a2200337 4500
001 - Número de control
control field ESSALUD
005 - Fecha y hora de la última transacción
Campo de control 20260903142036.0
007 - Tipo material - Descripcion fisica - info general
Tipo material - Descripcion fisica - info general ta
008 - Elementos de Longitud Fija - Información General
Elementos de Longitud Fija - Información t pe ||||| |||| 00| 0 spa d
040 ## - Origen de la Catalogación
Origen de la Catalogación BMG
041 ## - Idioma
Idioma eng
100 ## - Autor
Autor Gupta, Ashish O.
Rol del Autor Autor
9 (RLIN) 54539
245 ## - Titulo
Titulo Base editing of HBG1 and HBG2 promoters for sickle cell disease
300 ## - Páginas
Paginación páginas: 1824-1835
520 ## - Resumen
Resumen Background: Sickle cell disease is characterized by chronic hemolytic anemia and recurrent severe vaso-occlusive crises. Ristoglogene autogetemcel (risto-cel) includes autologous CD34+ hematopoietic stem and progenitor cells that have been base-edited to target the HBG1 and HBG2 promoters and inhibit BCL11A binding without altering BCL11A expression, yielding a switch in hemoglobin production from sickle hemoglobin (HbS) to antisickling fetal hemoglobin (HbF). Methods: In this phase 1–2 study, we enrolled patients 12 to 35 years of age with sickle cell disease who had had at least four severe vaso-occlusive crises in the 2 years before enrollment. After myeloablative conditioning with pharmacokinetically guided administration of busulfan, patients received a single infusion of risto-cel (at a dose of ≥3.0×106 viable CD34+ cells per kilogram of body weight). The primary efficacy end point was freedom from severe vaso-occlusive crises for 12 consecutive months, starting later than 60 days after the last red-cell transfusion. This interim analysis was unplanned; here, we describe safety, editing, engraftment, and hemoglobin production and the number of severe vaso-occlusive crises starting later than 60 days after the last red-cell transfusion. Results: A total of 31 patients received risto-cel and were followed for a mean of 6.6 months (range, 0.3 to 20.4). A median of one cycle (range, one to five) was required for stem-cell collection. Neutrophil engraftment occurred at a median of 17.5 days, and platelet engraftment at a median of 19 days. One patient died from idiopathic pneumonia syndrome. All 31 patients had at least one adverse event, 27 (87%) had an adverse event of grade 3 or higher, and 12 (39%) had a serious adverse event. At 6 months, the mean fraction of on-target edited alleles in peripheral blood was 67.4%, the mean HbF as a fraction of total hemoglobin was more than 60%, and the HbS as a fraction of total hemoglobin was less than 40% (among 13 patients); these levels were maintained throughout follow-up. No investigator-reported severe vaso-occlusive crises occurred later than 60 days after the last red-cell transfusion. Conclusions: Treatment with risto-cel was followed by rapid engraftment and durable expression of HbF and reduction in HbS. These data support further investigation of risto-cel to treat sickle cell disease.
650 ## - Temas - Descriptores
Temas - Descriptores MEDICINA DEL ADOLESCENTE
9 (RLIN) 5533
650 ## - Temas - Descriptores
Temas - Descriptores ANEMIA
9 (RLIN) 7417
650 ## - Temas - Descriptores
Temas - Descriptores ENFERMEDADES INFANTILES
9 (RLIN) 53890
650 ## - Temas - Descriptores
Temas - Descriptores GENÉTICA GENERAL
9 (RLIN) 54107
650 ## - Temas - Descriptores
Temas - Descriptores HEMATOLOGÍA
9 (RLIN) 7422
650 ## - Temas - Descriptores
Temas - Descriptores ONCOLOGÍA GENERAL
9 (RLIN) 54224
650 ## - Temas - Descriptores
Temas - Descriptores CÉLULAS MADRE
9 (RLIN) 42759
700 ## - Autor Personal
Autor Personal Sharma, Akshay
9 (RLIN) 54540
700 ## - Autor Personal
Autor Personal Frangoul, Haydar
9 (RLIN) 54541
700 ## - Autor Personal
Autor Personal Kanter, Julie
9 (RLIN) 54542
700 ## - Autor Personal
Autor Personal Mapara, Markus Y.
9 (RLIN) 54543
700 ## - Autor Personal
Autor Personal Dalal, Jignesh
9 (RLIN) 54544
700 ## - Autor Personal
Autor Personal Alavi, Asif
9 (RLIN) 54545
773 0# - Revista (Relacion con el numero)
Host Biblionumber 22717
Host Itemnumber 22676
Ciudad, Editorial Massachusetts NEJM Group
Codigo barras item/ejemplar NEJM015
Titulo de la Revista The New England Journal of Medicine
Número de control de registro ESSALUD
ISSN 0028-4793
942 ## - Elementos de Koha
Tipo de Documento Artículos
Fecha procesamiento 2026-08-31
Catalogador sqb

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