Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR = 6.6; p = 0.001 and OR = 3.3; p = 0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.

BMT Unit Department of Hematology IDIBAPS Hospital Clinic Institut Josep Carreras Barcelona Spain

Caen University Hospital Hematology Institute Caen France

Département d'Hématologie Hospices Civils de Lyon Pierre Bénite France

Department of Haematology and Oncology University Hospital Pilsen Pilsen Czech Republic

Department of Haematology Sheffield Teaching Hospitals NHS Foundation Trust Sheffield UK

Department of Hematology Hopitaux Universitaires Strasbourg Strasbourg France

Department of Hematology Institute of Hematology and Transfusion Medicine Warsaw Poland

Department of Hematology Saint Luc University Hospital Brussels Belgium

Department of Hematology School of Medicine University of Zagreb Zagreb Croatia

Department of Hematology The Collaborative Innovation Center of Hematology The 1st Affiliated Hospital of Soochow University Suzhou 215006 China

Department of Hematology University and CHU of Liège 4000 Liège Belgium

Department of Internal Medicine American University of Beirut Beirut 1107 2020 Lebanon

Department of Medical Oncology Dana Farber Cancer Institute Harvard Medical School Boston MA USA

Department of Pediatric Hematology Oncology and Stem Cell Transplantation Franz Josef Strauss Allee 11 University Hospital of Regensburg Regensburg Germany

Department of Pediatric Oncology and Haematology University Hospital of Rennes Rennes France

Division of Hematology Oncology Vanderbilt University Medical Center Nashville TN USA

Division of Infectious Diseases Brigham and Women's Harvard Medical School Boston MA USA

Heartlands Hospital Birmingham UK

Hematology and Bone Marrow Transplantation Division Chaim Sheba Medical Center Tel HaShomer Sackler School of Medicine Tel Aviv University Tel Aviv Israel

Hematology Department Complejo Asistencial Universitario de Salamanca IBSAL; Centro de Investigación del Cáncer IBMCC Salamanca Spain

Hematology Division University of Pisa Pisa Italy

HSCT Unit SC Ematologia Fondazione IRCCS Policlinico San Matteo University of Pavia Pavia Italy

Josep Carreras Foundation and Research Institute Hospital Clinic University of Barcelona Campus Barcelona Spain

Radboud University Medical Centre Nijmegen The Netherlands

Service d'hématologie Centre Hospitalier Universitaire 06000 Nice France

Sorbonne University Department of Clinical Hematology and Cellular Therapy Saint Antoine Hospital INSERM UMR 938 Paris France

Unit of Hematology and Bone Marrow Transplantation IRCCS San Raffaele Scientific Institute Vita Salute San Raffaele University Milan Italy

University Hospital Antwerp Edegem Belgium

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The Importance of New EBMT Criteria on the Diagnosis of Veno-Occlusive Liver Disease in Children