Hematopoietic stem cell transplant-associated thrombotic microangiopathy: current paradigm and novel therapies

Abstract

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) remains a difficult complication to address due to its high mortality rate, lack of standard diagnostic criteria and limited therapeutic options. Underscoring this challenge is the complex pathophysiology involved and multiple contributing factors that converge on a final pathway involving widespread endothelial injury and complement activation. In addressing our current understanding of TA-TMA, we highlight the risk factors leading to endothelial damage and a pathophysiological cascade that ensues. We have also compared the different definition criteria and biomarkers that can enable early intervention in TA-TMA patients. Current first-line management includes discontinuation or alteration of the immunosuppressive regimen, treatment of co-existing infectious and GVHD, aggressive hypertension control and supportive therapy. We discuss current pharmacological therapies, including newer agents that target the complement cascade and nitric oxide pathways.

A key step towards setting a benchmark for tackling transplant‐associated thrombotic microangiopathy

“…Many experts in the field have argued that with the use of rigorous, prospective monitoring using widely available laboratory tests and novel blood biomarkers, TA‐TMA can be detected in significantly more patients than previously appreciated (Jodele et al , ). Advances in the biological understanding of TA‐TMA and discovery of more specific and predictive biomarkers have led to more awareness and the potential for observer bias in recent years (Khosla et al , ). Despite the potential for observer bias, Epperla and colleagues did not find a change in TA‐TMA incidence over time during the study period (2008–2016), which again may reflect underreporting of TA‐TMA due to non‐standardised diagnostic criteria.…”

Pulmonary arterial hypertension and transplant-associated thrombotic microangiopathy in a child with neuroblastoma after autologous peripheral blood stem cell transplantation

“…replication occurs in approximately half of allogeneic HSCT recipients and may cause fever, skin rash, interstitial pneumonia, and encephalitis. 4,5 To date, however, HHV6associated pleurisy has not been recognized as a complication of HSCT. In this report, we describe an adult HSCT recipient who developed HHV6-associated pleurisy after an unrelated cord blood transplantation (CBT).…”

Peripheral blood schistocytes in the acute phase after allogeneic or autologous stem cell transplantation assessed by digital microscopy

“…Endothelial injury is a fundamental part of the pathogenesis of TA‐TMA . Acute graft‐versus‐host disease (aGVHD) is linked to TA‐TMA, as patients with aGVHD have a fourfold increase in odds of developing TA‐TMA, when compared to patients without aGVHD .…”

“…2,3 Endothelial injury is a fundamental part of the pathogenesis of TA-TMA. 4 Acute graft-versus-host disease (aGVHD) is linked to TA-TMA, as patients with aGVHD have a fourfold increase in odds of developing TA-TMA, when compared to patients without aGVHD. 5 Early detection of endothelial GVHD might help treat this complication and protect post-HSCT patients from the late complications of TA-TMA.…”