Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research

Schoettler, Michelle Long; Carreras, Enric; Cho, Byung-Sik; Dandoy, CE.; Ho, VT.; Jodele, Sonata; Moissev, I.; Sánchez-Ortega, Isabel; Srivastava, Alok; Atsuta, Yoshiko; Carpenter, Paul A.; Koreth, John; Kroger, N.; Ljungman, Per; Page, Kristin; Popat, Uday; Shaw, BE.; Sureda, Anna; Soiffer, Robert J.; Vasu, Sumithira

doi:10.1016/j.jtct.2022.11.015

Cited by 50 publications

(63 citation statements)

References 78 publications

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“…In 2022, an international expert group published consensus recommendations for TA‐TMA diagnostics using modified Jodele criteria (Table 1A). 1 The TA‐TMA diagnostic criteria proposed by Jodele et al are the only criteria derived from a prospective study that screened for TA‐TMA using all proposed laboratory markers and specifically evaluated disease presentation timelines. Using the original Jodele criteria, a patient must develop a minimum of four of seven diagnostic criteria for a diagnosis of TA‐TMA 3 .…”

Section: Diagnostic Criteria and Screeningmentioning

confidence: 99%

“…With many new complement blockers coming into clinical arena, investigators should work to combine efforts and perform larger, more impactful studies that can ultimately lead to universal recommendations. The harmonization of TA‐TMA definitions by the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia‐Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research hopefully will alleviate existing discrepancies and will aid future prospective studies 1 . Efforts are also needed to support the widespread availability of drug level testing for existing (e.g., eculizumab) and novel TA‐TMA therapies.…”

Section: Concluding Pointsmentioning

confidence: 99%

“…Prospective TA‐TMA screening and pharmacokinetics guided complement inhibitor use in select academic centers with a TA‐TMA research focus have drastically improved outcomes and provided a large source of contemporary information. As a result of these efforts, standardized diagnostic criteria for TA‐TMA were published in 2022 after consensus by the international expert team 1 …”

Section: Introductionmentioning

confidence: 99%

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Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

Jodele

Sabulski

2023

American J Hematol

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Over the last decade there have been numerous advances in both the diagnosis and treatment of transplant-associated thrombotic microangiopathy (TA-TMA). These are largely the result of an improved understanding of complement activation in TA-TMA and the ability to prevent end organ injury and death with timely initiation of complementblocking therapies. In this article, we review our current understanding of the pathophysiology of TA-TMA, particularly as it pertains to complement activation, endothelial injury, and clinical management. We then review novel complement-blocking therapies that are currently under investigation for use in TA-TMA, as well as discuss special considerations for complement-blocking therapy in hematopoietic stem cell transplant recipients. Through these reviews we aim to answer or at least provide an educated discussion on the most commonly posed TA-TMA management questions and dilemmas.

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Section: Diagnostic Criteria and Screeningmentioning

confidence: 99%

Section: Concluding Pointsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

Jodele

Sabulski

2023

American J Hematol

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“…Other underlying causes (conditioning regimen, calcineurin inhibitors, infections, and GVHD) contribute to a prothrombotic state, which may finally lead to microvasculature thrombosis [ 76 ]. TA-TMA diagnosis is constantly improving based on a novel consensus prompted by a better understanding of the pathophysiology of this syndrome [ 77 ].…”

Section: Complement Activation In Sos/vodmentioning

confidence: 99%

Molecular Advances in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease

Mavrikou

Chatzidimitriou

Skoura

et al. 2023

IJMS

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Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) detected in the liver has been considered a severe complication of hematopoietic stem cell transplantation (HSCT). SOS/VOD is characterized by hepatomegaly, right upper quadrant pain, jaundice, and ascites. The severe forms of the disease may result in multi-organ dysfunction (MOD) with a high mortality rate (>80%). The development of SOS/VOD can be rapid and unpredictable. Therefore, early identification and severity assessment is crucial in facilitating prompt diagnosis and timely treatment. Effective treatment and potential prophylaxis with defibrotide highlight the need for characterizing a sub-group of patients at high risk for SOS/VOD. Moreover, antibodies that are conjugated with calicheamicin, gemtuzumab, and inotuzumab ozogamicin, have led to renewed interest in this syndrome. Evaluation and management of serious adverse events associated with gemtuzumab and inotuzumab ozogamicin are recommended. We review hepatic-, transplant- and patient-related risk factors, criteria for diagnosis and grading classification, and SOS/VOD potential biomarkers. Furthermore, we examine pathogenesis, clinical presentation, diagnostic criteria, risk factors, prophylaxis, and treatment of SOS/VOD occurring post HSCT. Moreover, we aim to provide an up-to-date summary of molecular advances in the diagnosis and management of SOS/VOD. We performed a comprehensive review of the literature and examined the recently available data, mostly using the PubMed and Medline search engines for original articles published over the last decade. In the era of precision medicine, our review provides up-to-date knowledge of genetic or sera markers for SOS/VOD with the goal of identifying a subset of high-risk patients.

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“…Despite growing literature on the use of C5 inhibition for DI-TMA, a few noteworthy barriers remain. First, many labs do not measure plasma sC5b-9 levels (also known as soluble membrane attack complex) which are used to quantify terminal complement activation in TA-TMA, PNH and aHUS (16,17). Elevated sC5b-9 levels in a suspected DI-TMA would support in vivo terminal complement activation and the use of a terminal complement inhibitor.…”

mentioning

confidence: 99%

Peering into the darkness of drug-induced thrombotic microangiopathy: complement, are you in there?

Sabulski¹,

Jodele²

2023

J Gastrointest Oncol

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Cited by 50 publications

References 78 publications

Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

Molecular Advances in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease

Peering into the darkness of drug-induced thrombotic microangiopathy: complement, are you in there?

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