Incidence and Risk Factors of Transplantation-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis

Benschoten, Victoria Van; Roy, Cayla; Gupta, Rohit; Ouellette, Lara; Hingorani, Sangeeta; Li, Ang

doi:10.1016/j.jtct.2022.01.009

Cited by 12 publications

(5 citation statements)

References 35 publications

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“…HSCT-TMA is a distinct type of thrombotic microangiopathy, following HSCT, and is characterized by the clinical triad of thrombocytopenia, macroangiopathic hemolytic anemia, and target-organ damage [27]. In a meta-analysis published by Van Benschoten et al, the pooled incidence of HSCT-TMA after alloHSCT was 12% (95% confidence interval, range 9%-16%) [28]. HSCT-TMA can complicate both allogeneic and autologous HSCT, mainly affecting pediatric patients with neuroblastoma, but it is more prevalent in alloHSCT [29].…”

Section: Hsct-tma: Complement Dysregulation and Endothelial Dysfuncti...mentioning

confidence: 99%

“…A three-hit hypothesis has been described for the pathogenesis of HSCT-TMA [12]. The first hit includes underlying predisposing factors: female sex, African American race, non-malignant hematological disorder, history of previous HSCT, and genetic variants [7,28]. The second hit of transplant-related risk factors, such as transplant conditioning regimen-related toxicity, total-body irradiation, unrelated donor transplantation, and human leukocyte antigen (HLA) mismatch, leads to endothelial injury, and a procoagulant state is developed [30,31].…”

Section: Hsct-tma: Complement Dysregulation and Endothelial Dysfuncti...mentioning

confidence: 99%

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Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Evangelidis,

Kalmoukos

et al. 2024

CIMB

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Hematopoietic stem cell transplantation (HSCT) remains a cornerstone in the management of patients with hematological malignancies. Endothelial injury syndromes, such as HSCT-associated thrombotic microangiopathy (HSCT-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (SOS/VOD), and capillary leak syndrome (CLS), constitute complications after HSCT. Moreover, endothelial damage is prevalent after immunotherapy with chimeric antigen receptor-T (CAR-T) and can be manifested with cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Our literature review aims to investigate the genetic susceptibility in endothelial injury syndromes after HSCT and CAR-T cell therapy. Variations in complement pathway- and endothelial function-related genes have been associated with the development of HSCT-TMA. In these genes, CFHR5, CFHR1, CFHR3, CFI, ADAMTS13, CFB, C3, C4, C5, and MASP1 are included. Thus, patients with these variations might have a predisposition to complement activation, which is also exaggerated by other factors (such as acute graft-versus-host disease, infections, and calcineurin inhibitors). Few studies have examined the genetic susceptibility to SOS/VOD syndrome, and the implicated genes include CFH, methylenetetrahydrofolate reductase, and heparinase. Finally, specific mutations have been associated with the onset of CRS (PFKFB4, CX3CR1) and ICANS (PPM1D, DNMT3A, TE2, ASXL1). More research is essential in this field to achieve better outcomes for our patients.

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Section: Hsct-tma: Complement Dysregulation and Endothelial Dysfuncti...mentioning

confidence: 99%

Section: Hsct-tma: Complement Dysregulation and Endothelial Dysfuncti...mentioning

confidence: 99%

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Evangelidis,

Kalmoukos

et al. 2024

CIMB

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“…Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication that is encountered early in the post-HCT phase. The incidence of TA-TMA in children is 16%, with a median onset of 47 days post-transplant [ 18 ]. Risk factors for TA-TMA include acute GVHD, infectious process (especially viral), mismatched donor, multiple HCTs, and myeloablative conditioning [ 18 ].…”

Section: Special Disease Conditions Post Hct That Are Associated With...mentioning

confidence: 99%

“…The incidence of TA-TMA in children is 16%, with a median onset of 47 days post-transplant [ 18 ]. Risk factors for TA-TMA include acute GVHD, infectious process (especially viral), mismatched donor, multiple HCTs, and myeloablative conditioning [ 18 ]. The pathophysiology of TA-TMA involves an initial endothelial injury triggered by factors such as chemotherapy or infection that results in an increase in the proinflammatory cytokines, procoagulant factors, and soluble adhesion molecules.…”

Section: Special Disease Conditions Post Hct That Are Associated With...mentioning

confidence: 99%

Kidney Injury in Children after Hematopoietic Stem Cell Transplant

2023

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Hematopoietic cell transplant (HCT), used for treatment of many malignant and non-malignant pediatric diseases, is associated with serious complications, limiting this therapy’s benefit. Acute kidney injury (AKI), seen often after HCT, can occur at different stages of the transplant process and contributes to morbidity and mortality after HCT. The etiology of AKI is often multifactorial, including kidney hypoperfusion, nephrotoxicity from immunosuppressive and antimicrobial agents, and other transplant-related complications such as transplant-associated thrombotic microangiopathy and sinusoidal obstructive syndrome. Early recognition of AKI is crucial to prevent further AKI and associated complications. Initial management includes identifying the etiology of AKI, preventing further kidney hypoperfusion, adjusting nephrotoxic medications, and preventing fluid overload. Some patients will require further support with kidney replacement therapy to manage fluid overload and AKI. Biomarkers of AKI, such as neutrophil gelatinase-associated lipocalin can aid in detecting AKI before a rise in serum creatinine, allowing earlier intervention. Long-term kidney dysfunction is also prominent in this population. Therefore, long-term follow-up and monitoring of renal function (glomerular filtration rate, microalbuminuria) is required along with management of hypertension, which can contribute to chronic kidney disease.

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“…However, in patients who recently received HSCT, the listed signs can overlap with other conditions and/or may be difficult to identify. For this reason, the epidemiology of TA-TMA remains poorly defined: its frequency ranges from as low as 3% to as high as 39% and the related case-fatality rate has been reported as high as 84%, depending on the definition criteria [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy

et al. 2022

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Thrombotic microangiopathy (TMA) is a complication that may occur after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) and is conventionally called transplant-associated thrombotic microangiopathy (TA-TMA). Despite the many efforts made to understand the mechanisms of TA-TMA, its pathogenesis is largely unknown, its diagnosis is challenging and the case-fatality rate remains high. The hallmarks of TA-TMA, as for any TMA, are platelet consumption, hemolysis, and organ dysfunction, particularly the kidney, leading also to hypertension. However, coexisting complications, such as infections and/or immune-mediated injury and/or drug toxicity, together with the heterogeneity of diagnostic criteria, render the diagnosis difficult. During the last 10 years, evidence has been provided on the involvement of the complement system in the pathophysiology of TA-TMA, supported by functional, genetic, and therapeutic data. Complement dysregulation is believed to collaborate with other proinflammatory and procoagulant factors to cause endothelial injury and consequent microvascular thrombosis and tissue damage. However, data on complement activation in TA-TMA are not sufficient to support a systematic use of complement inhibition therapy in all patients. Thus, it seems reasonable to propose complement inhibition therapy only to those patients exhibiting a clear complement activation according to the available biomarkers. Several agents are now available to inhibit complement activity: two drugs have been successfully used in TA-TMA, particularly in pediatric cases (eculizumab and narsoplimab) and others are at different stages of development (ravulizumab, coversin, pegcetacoplan, crovalimab, avacopan, iptacopan, danicopan, BCX9930, and AMY-101).

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Incidence and Risk Factors of Transplantation-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis

Cited by 12 publications

References 35 publications

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Kidney Injury in Children after Hematopoietic Stem Cell Transplant

Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy

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