Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Thomas Luft, Peter Dreger, Aleksandar Radujkovic, Thomas Luft, Peter Dreger, Aleksandar Radujkovic

Abstract

Allogeneic hematopoietic stem cell transplantation (alloSCT) carries the promise of cure for many malignant and non-malignant diseases of the lympho-hematopoietic system. Although outcome has improved considerably since the pioneering Seattle achievements more than 5 decades ago, non-relapse mortality (NRM) remains a major burden of alloSCT. There is increasing evidence that endothelial dysfunction is involved in many of the life-threatening complications of alloSCT, such as sinusoidal obstruction syndrome/venoocclusive disease, transplant-associated thrombotic microangiopathy, and refractory acute graft-versus host disease. This review delineates the role of the endothelium in severe complications after alloSCT and describes the current status of search for biomarkers predicting endothelial complications, including markers of endothelial vulnerability and markers of endothelial injury. Finally, implications of our current understanding of transplant-associated endothelial pathology for prevention and management of complications after alloSCT are discussed.

Conflict of interest statement

T.L. and A.R. have nothing to disclose. P.D.: consultancy for AbbVie, AstraZeneca, bluebird bio, Gilead, Janssen, Novartis, Riemser, Roche; speakers bureau for AbbVie, AstraZeneca, Gilead, Novartis, Riemser, Roche; research support from Riemser.

© 2021. The Author(s).

Figures

Fig. 1. Endothelial challenges during allogeneic stem…
Fig. 1. Endothelial challenges during allogeneic stem cell transplantation.
Endothelial cells experience stressing influences before, during, and after alloSCT. In the pre-transplantation period, patient-specific endothelial vulnerability and pre-established endothelial damage set the stage for the subsequent challenges during conditioning therapy, immune suppression, and post-transplant complications.
Fig. 2. Hypothetical link between pre-established endothelial…
Fig. 2. Hypothetical link between pre-established endothelial cell injury and endothelial vulnerability with mortality after alloSCT.
Conditioning therapy, immunosuppressive drugs, and post-transplant complications increase endothelial cell distress. In most patients, the threshold to substantial endothelial dysfunction, disturbed microcirculation/microangiopathy and death will not be trespassed (patient 1). Patient 2 with pre-established endothelial cell injury responds similarly to the additional endothelial strains in the context of alloSCT. However, the threshold will be reached due to a lower area of resilience. Patient 3 without pre-established endothelial injury responds more vigorously to the same endothelial challenges due to a patient-specific endothelial vulnerability. The net effect is again an infringement of the threshold and severe complications/death.

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Source: PubMed

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