Terminal complement blockade by humanised monoclonal antibody eculizumab has been used to treat transplantation-associated thrombotic microangiopathy (TA-TMA) in recent years. This retrospective international study conducted by the Paediatric Diseases (PDWP) and Inborn Error Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT) describes outcome and response of 82 paediatric patients from 29 centres who developed TA-TMA and were treated with eculizumab between January 2014 and May 2019. The median time from hematopoietic stem cell transplantation (HSCT) to TA-TMA manifestation was 92 days (range: 7-606) and from TA-TMA diagnosis to the start of eculizumab treatment 6 days (range: 0-135). Most patients received eculizumab weekly (72%, n = 55) with a standard weight (kg)-based dose (78%, n = 64). Six months from beginning of eculizumab therapy, the cumulative incidence of TA-TMA resolution was 36.6% (95% CI: 26.2-47) and the overall survival (OS) was 47.1% (95% CI: 35.9-57.5). All 43 patients with unresolved TA-TMA died. The cause of death was HSCT-related in 41 patients. This study also documents poor outcome of patients without aGvHD and their frequent concomitant viral infections. Considering recent publications, intensified eculizumab dosing and complement monitoring could potentially improve upon outcomes observed in this study.

Bristol Royal Hospital for Children Bristol United Kingdom

Central Hospital of Southern Pest Budapest Hungary

EBMT Paris study office Paris France

Fondazione MBBM Milano Bicocca University Monza Italy

Great North Children's Hospital Newcastle Upon Tyne United Kingdom

Hospital Infantil La Paz Madrid Spain

Hospital Infantil Universitario 'Niño Jesus' Madrid Spain

Hospital Universitari Vall d'Hebron Barcelona Spain

Institut d'Hematologie et d'Oncologie Pediatrique Lyon France

Institute for Immunodeficiency Center for Chronic Immunodeficiency Faculty of Medicine Center for Pediatrics and Adolescent Medicine Department of Pediatric Hematology and Oncology Medical Center University of Freiburg Freiburg Germany

IRCSS Institute G Gaslini Genova Italy

Leeds Children's Hospital Leeds United Kingdom

National Institute of Children's Diseases and Comenius Univeristy Bratislava Slovakia

NIHR Great Ormond Street Hospital BRC UCL Institute of Immunity and Transplantation Royal Free hospital London OH USA

Oslo University Hospital Oslo Norway

Paediatric Onco Haematology Regina Margherita Children's Hospital University of Torino Turin Italy

Pediatric Hematology Oncology Azienda Ospedaliera Universitaria Integrata Verona Verona Italy

Pediatric immune hematology and rheumatology unit Hospital Necker enfants maladies Assistance publique hopitaux de Paris Paris University Paris France

Princess Maxima centre for pediatric oncology Utrecht University Children's Hospital Utrecht Netherlands

Sahlgrenska Univ Hospital Goeteborg Sweden

Saint Antoine Hospital Sorbonne University Paris France

Schneider Children's Medical Center of Israel Sackler Faculty of Medicine Tel Aviv University Petach Tikva Israel

Semmelweis University Budapest Hungary

Sheffield Children's Hospital NHS Foundation Trust Sheffield United Kingdom

St Anna Children's Hospital and Children's Cancer Research Institute Medical University of Vienna Vienna Austria

Texas Transplant Institute Methodist Children's Hospital San Antonio TX USA

The Royal Children's Hospital Melbourne Melbourne VIC Australia

UCSF Benioff Children's Hospital San Francisco CA USA

University Children's Hospital Basel Basel Switzerland

University children's hospital Ljubljana Ljubljana Slovenia

University Children's Hospital Würzburg Germany

University Hospital Motol Charles University Prague Czech Republic

University of Regensburg Regensburg Germany

Willem Alexander Children's Hospital Department of Pediatrics Leiden University Medical Center Leiden Netherlands

Wroclaw Medical University Wroclaw Poland

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