Putting function back in dysfunction: Endothelial diseases and current therapies in hematopoietic stem cell transplantation and cellular therapies

Sumransub, Nuttavut; Jurdi, Najla El; Chiraphapphaiboon, Wannasiri; Maakaron, Joseph

doi:10.1016/j.blre.2021.100883

Cited by 8 publications

(3 citation statements)

References 126 publications

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“…During allo-HCT, ECs can be directly damaged and/or activated via multiple mechanismsi) chemotherapy and radiation included in the conditioning regimen; ii) cytokines released by injured tissues; iii) translocation of endotoxins through the damaged gastrointestinal tract as well as iv) immunosuppressive prophylactic regimens used to prevent acute GVHD, Figure 1. Apart from these early factors, ECs are also a target of alloreactive donor T cells that recognize the HLA mismatched antigens on ECs and mediate EC damage (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Role of endothelial cells in graft-versus-host disease

et al. 2022

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To date, the only curative treatment for high-risk or refractory hematologic malignancies non-responsive to standard chemotherapy is allogeneic hematopoietic transplantation (allo-HCT). Acute graft-versus-host disease (GVHD) is a donor T cell-mediated immunological disorder that is frequently fatal and the leading cause of non-relapse mortality (NRM) in patients post allo-HCT. The pathogenesis of acute GVHD involves recognition of minor and/or major HLA mismatched host antigens by donor T cells followed by expansion, migration and finally end-organ damage due to combination of inflammatory cytokine secretion and direct cytotoxic effects. The endothelium is a thin layer of endothelial cells (EC) that line the innermost portion of the blood vessels and a key regulator in vascular homeostasis and inflammatory responses. Endothelial cells are activated by a wide range of inflammatory mediators including bacterial products, contents released from dying/apoptotic cells and cytokines and respond by secreting cytokines/chemokines that facilitate the recruitment of innate and adaptive immune cells to the site of inflammation. Endothelial cells can also be damaged prior to transplant as well as by alloreactive donor T cells. Prolonged EC activation results in dysfunction that plays a role in multiple post-transplant complications including but not limited to veno-occlusive disease (VOD), transplant associated thrombotic microangiopathy (TA-TMA), and idiopathic pneumonia syndrome. In this mini review, we summarize the biology of endothelial cells, factors regulating EC activation and the role of ECs in inflammation and GVHD pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Role of endothelial cells in graft-versus-host disease

et al. 2022

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“…[36][37][38] ICANS is mostly reversible; however, recent clinical observations point to a small subset of patients who might experience subtle, prolonged, neurological manifestations including cognitive dysfunction. 39 Treatment is predominantly with corticosteroids in addition to supportive care (antiepileptics and intensive care unit (ICU) level care/intubation if needed).…”

Section: Immune Effector Cell Associated Neurotoxicity Syndrome (Icans)mentioning

confidence: 99%

“…Similar to CRS, it can vary in severity from a simple headache, tremor, or word-finding difficulties, at its mildest, to confusion, aphasia, seizures, brain edema, and death in the most severe forms 363738. ICANS is mostly reversible; however, recent clinical observations point to a small subset of patients who might experience subtle, prolonged, neurological manifestations including cognitive dysfunction 39. Treatment is predominantly with corticosteroids in addition to supportive care (antiepileptics and intensive care unit (ICU) level care/intubation if needed).…”

Section: Toxicitiesmentioning

confidence: 99%

Chimeric antigen receptor T cell therapy for cancer: clinical applications and practical considerations

Maakaron

Jurdi

2022

BMJ

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Chimeric antigen receptor T cells have revolutionized the treatment of hematological malignancies during the past five years, boasting impressive response rates and durable remissions for patients who previously had no viable options. In this review, we provide a brief historical overview of their development. We focus on the practical aspects of a patient’s journey through this treatment and the unique toxicities and current best practices to manage those. We then discuss the key registration trials that have led to approvals for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma (MCL), and multiple myeloma. Finally, we consider the future development and research directions of this cutting edge therapy.

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The critical role of endothelial cell in the toxicity associated with chimeric antigen receptor T cell therapy and intervention strategies

Zhang,

Zhu,

Xiao

2024

Ann Hematol

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Chimeric antigen receptor (CAR)-T cell therapy has shown promising results in patients with hematological malignancies. However, many patients still have poor prognoses or even fatal outcomes due to the life-threatening toxicities associated with the therapy. Moreover, even after improving the known influencing factors (such as number or type of CAR-T infusion) related to CAR-T cell infusion, the results remain unsatisfactory. In recent years, it has been found that endothelial cells (ECs), which are key components of the organization, play a crucial role in various aspects of immune system activation and inflammatory response. The levels of typical markers of endothelial activation positively correlated with the severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS), suggesting that ECs are important targets for intervention and toxicity prevention. This review focuses on the critical role of ECs in CRS and ICANS and the intervention strategies adopted.

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Putting function back in dysfunction: Endothelial diseases and current therapies in hematopoietic stem cell transplantation and cellular therapies

Cited by 8 publications

References 126 publications

Role of endothelial cells in graft-versus-host disease

Role of endothelial cells in graft-versus-host disease

Chimeric antigen receptor T cell therapy for cancer: clinical applications and practical considerations

The critical role of endothelial cell in the toxicity associated with chimeric antigen receptor T cell therapy and intervention strategies

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