Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients

Summary

Hematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TMA) is an understudied complication of HCT that significantly affects transplant related morbidity and mortality. The investigators hypothesize that early intervention with complement blocker eculizumab will double survival in HCT recipients with high risk TMA, as compared to historical untreated controls. An optimal eculizumab dosing schedule can be determined for this population through eculizumab pharmacokinetic/pharmacodynamic (PK/PD) testing.

Timeline

Start

2018-08-03

Primary completion

2022-04-04

Completion

2022-06-01

Outcome

Met primary endpoint

paper Primary and secondary study endpoints were met by demonstrating survival of 71% (P < .0001) 6 months after hrTMA diagnosis. PMID 37946262 ↗

registry analysis (equivalence test); Eculizumab; p <0.0001; Proportion 0.714; binomial test; note: The a priori threshold was 0.05. NCT03518203 ↗

Publications

• Jodele S, Dandoy CE, Aguayo-Hiraldo P, Lane A, Teusink-Cross A, Sabulski A, Mizuno K, Laskin BL, Freedman J, Davies SM. A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation-associated TMA. Blood. 2024 Mar 21;143(12):1112-1123. doi: 10.1182/blood.2023022526.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Eculizumab	Monoclonal antibody	—	Intravenous

Indications