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A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation-associated TMA.
Jodele, Sonata; Dandoy, Christopher E; Aguayo-Hiraldo, Paibel; Lane, Adam; Teusink-Cross, Ashley; Sabulski, Anthony; Mizuno, Kana; Laskin, Benjamin L; Freedman, Jason; Davies, Stella M.
Afiliación
  • Jodele S; Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
  • Dandoy CE; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
  • Aguayo-Hiraldo P; Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
  • Lane A; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
  • Teusink-Cross A; Division of Bone Marrow Transplantation, Children's Hospital of Los Angeles, Los Angeles, CA.
  • Sabulski A; Keck School of Medicine of University of Southern California, Los Angeles, CA.
  • Mizuno K; Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
  • Laskin BL; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
  • Freedman J; Department of Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
  • Davies SM; Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Disease Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Blood ; 143(12): 1112-1123, 2024 Mar 21.
Article en En | MEDLINE | ID: mdl-37946262
ABSTRACT: High-risk, complement mediated, untreated transplant-associated thrombotic microangiopathy (hrTMA) has dismal outcomes due to multi-organ dysfunction syndrome (MODS). The complement C5 blocker eculizumab shows promising results in hrTMA, but has not been prospectively studied in hematopoietic stem cell transplant (HCT) recipients. We performed the first multi-institutional prospective study in children and young adults to evaluate eculizumab as an early targeted intervention for hrTMA/MODS. We hypothesized that eculizumab would more than double survival in HCT recipients with hrTMA, compared to our prior study of prospectively screened, untreated hrTMAs serving as historical controls. HrTMA features (elevated terminal complement (sC5b-9) and proteinuria measured by random urine protein/creatinine ratio (≥1mg/mg)) were required for inclusion. The primary endpoint was survival at 6 six-months from hrTMA diagnosis. Secondary endpoints were cumulative incidence of MODS 6 months after hrTMA diagnosis and 1-year posttransplant survival. Eculizumab dosing included intensive loading, induction, and maintenance phases for up to 24 weeks of therapy. All 21 evaluated study subjects had MODS. Primary and secondary study endpoints were met by demonstrating survival of 71% (P < .0001) 6 months after hrTMA diagnosis and 62% 1 year after transplant. Of fifteen survivors, 11 (73%) fully recovered organ function and are well. Our study demonstrates significant improvement in survival and recovery of organ function in hrTMA using an intensified eculizumab dosing and real time biomarker monitoring. This study serves as a benchmark for planning future studies that should focus on preventative measures or targeted therapy to be initiated prior to organ injury. This trial was registered at www.clinicaltrials.gov as #NCT03518203.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Microangiopatías Trombóticas Límite: Adult / Child / Humans Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Microangiopatías Trombóticas Límite: Adult / Child / Humans Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos