Use of haematopoietic cell transplantation (HCT) in the treatment of haematologic and neoplastic diseases may lead to life-threatening complications that cause substantial morbidity and mortality if untreated. In addition to patient- and disease-related factors, toxicity associated with HCT puts patients at risk for complications that share a similar pathophysiology involving endothelial cells (ECs). Normally, the endothelium plays a role in maintaining homeostasis, including regulation of coagulation, vascular tone, permeability and inflammatory processes. When activated, ECs acquire cellular features that may lead to phenotypic changes that induce procoagulant, pro-inflammatory and pro-apoptotic mediators leading to EC dysfunction and damage. Elevated levels of coagulation factors, cytokines and adhesion molecules are indicative of endothelial dysfunction, and endothelial damage may lead to clinical signs and symptoms of pathological post-HCT conditions, including veno-occlusive disease/sinusoidal obstruction syndrome, graft-versus-host disease, transplant-associated thrombotic microangiopathy and idiopathic pneumonia syndrome/diffuse alveolar haemorrhage. The endothelium represents a rational target for preventing and treating HCT complications arising from EC dysfunction and damage. Additionally, markers of endothelial damage may be useful in improving diagnosis of HCT-related complications and monitoring treatment effect. Continued research to effectively manage EC activation, injury and dysfunction may be important in improving patient outcomes after HCT.
|Number of pages||12|
|Journal||British Journal of Haematology|
|State||Published - Aug 1 2020|
Bibliographical noteFunding Information:
GCH has stocks/ownership interests in Sangamo Bioscience, Axim Biotechnologies, Juno Therapeutics, Kite Pharma, Novartis, Insys Therapeutics, Abbvie, GW Pharmaceuticals, Cardinal Health, Immunomedics, Endocyte, Clovis Oncology, Cellectis, Aetna, CVS Health, Celgene, Bluebird Bio, Bristol‐Myers Squibb/Medarex, crispr Therapeutics, IDEXX Laboratories, Johnson & Johnson, Pfizer, Procter & Gamble, Vertex, Bayer, Scotts‐Miracle, Charlottes Webb CWBHF, Almmune Therapeutics Inc AIMT, Medical PPTYS TR Inc. MPW, Caretrust Reit Inc CTRE, ANGI Homeservices Inc ANGI, and Bayer AG BAYRY; has served in advisory/consulting roles for Pfizer, Kite Pharma, Incyte, and Jazz Pharmaceuticals; has received research funding from Takeda, Astellas, Incyte, Jazz Pharmaceuticals, and Pharmacyclics; and has received travel, accommodations, and/or expense reimbursement from Kite Pharma, Incyte, Pfizer, Falk Foundation, Jazz Pharmaceuticals, and Astellas Pharma. NC has nothing to disclose.
Medical writing and editorial support were provided by Michelle McDermott, PharmD, and Michael Whitley, PhD, of SciFluent Communications, and were financially supported by Jazz Pharmaceuticals.
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd
- chimeric antigen receptor T-cell (CAR-T) therapy
- endothelial cell dysfunction
- endothelial-related disorders
- haematopoietic cell transplantation
- treatment for post-HCT complications
ASJC Scopus subject areas