Successful Treatment of Transplant Associated Thrombotic Microangiopathy (TA-TMA) with Low Dose Defibrotide

Devadas, Santhosh Kumar; Toshniwal, Manoj; Bagal, Bhausaheb; Khattry, Navin

doi:10.1007/s12288-017-0904-y

Cited by 12 publications

(6 citation statements)

References 18 publications

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“…Another supportive treatment for HSCT-TMA, defibrotide is approved for the treatment of hepatic veno-occlusive disease, also known as sinusoidal obstruction syndrome, a complication following HSCT [63]. Retrospective analyses and case series of defibrotide therapy have reported responses in patients with HSCT-TMA [46,[64][65][66][67] and a prospective pilot study suggested prophylactic defibrotide use reduces the incidence of HSCT-TMA [68], but increased bleeding and hemorrhagic complications were reported with defibrotide use in these studies [65][66][67][68]. Historically, another approach to treat HSCT-TMA has been to withhold or modify calcineurin inhibitors [22], but recent data have shown that continuing immunosuppressants does not impact resolution of HSCT-TMA or survival in patients with HSCT-TMA.…”

Section: Supportive Therapymentioning

confidence: 99%

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists

Mahmoudjafari

Alencar

Alexander

et al. 2023

Bone Marrow Transplant

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Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a severe and potentially life-threatening complication. HSCT-TMA is often underdiagnosed due to multifactorial pathophysiology and a historic lack of standard diagnostic criteria. Identification of the multi-hit hypothesis and the key role of the complement system, particularly the lectin pathway of complement, has led to development of treatments targeting the underlying pathogenesis of HSCT-TMA. Additional research is ongoing to investigate the efficacy and safety of these targeted therapies in patients with HSCT-TMA. Advanced practice providers (APPs; nurse practitioners and physician assistants) and pharmacists are critical members of the multidisciplinary HSCT team and ensure management of patients throughout the continuum of care. Additionally, pharmacists and APPs can improve patient care through medication management of complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives to improve outcomes. Understanding the presentation, prognosis, pathophysiology, and treatment options for HSCT-TMA can improve each of these efforts.

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Section: Supportive Therapymentioning

confidence: 99%

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists

Mahmoudjafari

Alencar

Alexander

et al. 2023

Bone Marrow Transplant

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“…Furthermore, no major adverse events were noted during Defibrotide treatment [ 14 ]. Another study explored the potential effect of a low dose of Defibrotide on TA-TMA in a very limited number of patients and demonstrated that Defibrotide was able to induce remission in all cases, even at a lower dose [ 65 ]. Along the same lines, Yeates et al reported resolution of TA-TMA symptoms in 76% of a small cohort of 17 patients [ 66 ], whereas Bohl et al reported a response rate of 61% in patients treated with Defibrotide with or without TPE and/or Rituximab [ 67 ].…”

Section: Current Therapeutic Approachesmentioning

confidence: 99%

Transplant-Associated Thrombotic Microangiopathy in the Context of Allogenic Hematopoietic Stem Cell Transplantation: Where We Stand

Λαζανά

2023

IJMS

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Transplant-associated thrombotic microangiopathy (TA-TMA) constitutes a significant contributor to the increased morbidity and mortality after allogenic hematopoietic stem cell transplantation (allo-HSCT). TA-TMA is a heterogenous disease, characterized by the triad of endothelial cell activation, complement dysregulation and microvascular hemolytic anemia, which may affect all organs. The lack of consensus diagnostic criteria, along with the common clinical features mimicking other diseases that complicate allo-HSCT, make the diagnosis of TA-TMA particularly challenging. Significant effort has been made to recognize specific risk factors predisposing to the development of TA-TMA and to identify serum biomarkers predicting the development of the disease. With regard to treatment, therapeutic plasma exchange (TPE) has been traditionally used, although with doubtful efficacy. On the other hand, the pivotal role of complement activation in the pathophysiology of TA-TMA has led to the exploration of the therapeutic potential of complement inhibitors in this setting. Eculizumab has been proposed as a first-line therapeutic agent in TA-TMA, owing to the very promising results in both pediatric and adult clinical trials. Pharmacokinetic and pharmacodynamic studies and CH50 levels are of paramount importance in the allo-HSCT setting, as a different dosing schedule (more intensive—in dose and frequency—at the beginning) seems to be required for successful outcomes. Furthermore, Narsoplimab, a MASP-2 inhibitor, recently received a Breakthrough Therapy Designation from the FDA for the treatment of TA-TMA after allo-HSCT. Finally, the decision to withdraw the CNIs, although initially advised by the Bone and Marrow Transplant Clinical Trials Network Committee, remains debatable owing to the controversial results of recent clinical trials. This review summarizes the current updates on pathophysiology, diagnosis and therapeutic approaches and emphasizes future goals and perspectives.

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“…Defibrotide use has been explored in TM-TMA; in a limited number of patients affected with TM-TMA, the administration of a low dosage of defibrotide induced disease remission in all cases [181]. In a small study (ClinicalTrials.gov NCT03384693), administration of defibrotide as prophylaxis of TA-TMA resulted in very low NRM.…”

Section: Therapeutic Interventions For Ec Dysfunction 41 Defibrotidementioning

confidence: 99%

Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: A Review Based on Physiopathology

Milone

Bellofiore

Leotta

et al. 2022

JCM

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Endothelial dysfunction (ED) is frequently encountered in transplant medicine. ED is an argument of high complexity, and its understanding requires a wide spectrum of knowledge based on many fields of basic sciences such as molecular biology, immunology, and pathology. After hematopoietic stem cell transplantation (HSCT), ED participates in the pathogenesis of various complications such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), graft-versus-host disease (GVHD), transplant-associated thrombotic microangiopathy (TA-TMA), idiopathic pneumonia syndrome (IPS), capillary leak syndrome (CLS), and engraftment syndrome (ES). In the first part of the present manuscript, we briefly review some biological aspects of factors involved in ED: adhesion molecules, cytokines, Toll-like receptors, complement, angiopoietin-1, angiopoietin-2, thrombomodulin, high-mobility group B-1 protein, nitric oxide, glycocalyx, coagulation cascade. In the second part, we review the abnormalities of these factors found in the ED complications associated with HSCT. In the third part, a review of agents used in the treatment of ED after HSCT is presented.

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Successful Treatment of Transplant Associated Thrombotic Microangiopathy (TA-TMA) with Low Dose Defibrotide

Cited by 12 publications

References 18 publications

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists

Transplant-Associated Thrombotic Microangiopathy in the Context of Allogenic Hematopoietic Stem Cell Transplantation: Where We Stand

Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: A Review Based on Physiopathology

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