Abstract
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.
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MM reports grants and lecture honoraria from Janssen, Sanofi, and Jazz Pharmaceuticals; lecture honoraria from Celgene, Amgen, Bristol-Myers Squibb, Takeda, and Pfizer; and grants from Roche, all outside the submitted work. JAS reports lecture honoraria from Jazz, Janssen, Sanofi, Gilead and Mallinckrodt, and chairing NHS England Specialised Commissioning Clinical Reference Group for Blood and Marrow Transplantation, all outside the submitted work. FB has received travel grants and/or speaker honoraria from Celgene, AbbVie, Novartis, Pfizer and Sanofi. PJ has received travel grants and/or lecture honoraria from Novartis, Bristol-Myers Squib and Janssen, all outside the submitted work
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Bazarbachi, A.H., Al Hamed, R., Labopin, M. et al. Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party. Bone Marrow Transplant 56, 917–927 (2021). https://doi.org/10.1038/s41409-020-01135-3
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DOI: https://doi.org/10.1038/s41409-020-01135-3