Algorithm enables prompt response to high-risk cases of transplant-associated thrombotic microangiopathy (TMA)
After children undergo hematopoietic cell transplantation (HSCT), one of the most severe complications they can develop is thrombotic microangiopathy (TMA). This condition can trigger a cascade of events leading to potentially fatal multi-organ injury.
Prompt clinical intervention can save lives, but only if TMA is detected in its earliest stages. In an important paper published in the journal Blood, a research team led by Sonata Jodele, MD, Division of Bone Marrow Transplantation and Immune Deficiency, reports developing an algorithm that can provide the information clinicians need to act.
The researchers prospectively evaluated 100 HSCT recipients to track TMA incidence and outcomes. They found 39 children who met criteria for TMA. These children had a 43.6 percent non-relapse mortality rate at one year post-transplant, compared to 7.8 percent mortality among children who did not develop TMA.
The team observed that those who died after TMA diagnosis had a greater degree of anemia, higher risk of proteinuria, and were more likely to have evidence of terminal complement activation. Elevated levels of sC5b-9 were present in nearly all subjects with TMA who died but in only about half of those who survived. In contrast, kidney dysfunction assessed by serum creatinine was a very late marker of TMA.
The paper details a series of daily, twice weekly and weekly tests that can detect early TMA markers. Specifically, proteinuria >30 mg/dL as measured by routine dipstick and hypertension >95th percentile were the earliest signs of TMA, along with elevated lactate dehydrogenase (LDH).
These data suggest that complement activation plays a significant role in the pathogenesis of severe TMA after HSCT. The team recommends that patients with proteinuria and evidence of complement activation should be considered for treatment with eculizumab, a humanized monoclonal antibody that functions as a terminal complement inhibitor.
