Eculizumab Improves Survival When Stem Cell Transplant Patients Develop High-Risk TA-TMA

Published March 2020 | Blood

Transplant-associated thrombotic microangiopathy (TA-TMA) is one of the most dangerous complications that can occur in patients receiving hematopoietic stem cell transplant (HSCT). It occurs in about 30% of patients, and when untreated, can have a mortality rate exceeding 80%.

Closer study of TA-TMA in recent years has revealed that an over-activated complement system drives severe organ damage, especially in the kidney. This information prompted a multidisciplinary team of experts at Cincinnati Children’s to explore whether the complement blocking drug eculizumab could help.

The research was led by first author Sonata Jodele, MD, senior author Stella Davies, MBBS, PhD, MRCP, and 12 co-authors from several divisions at Cincinnati Children’s.

The team reported encouraging results from treating 64 HSCT recipients with a high risk for TA-TMA with the drug. At one year post-transplant, the survival rate for treated patients improved to 66%; up from 16% in a previously reported untreated cohort.

Patients who responded received a median of 11 doses of eculizumab, and their TA-TMA resolved within a median of 66 days. Those who did not respond tended to have more severe complement activation, and some had intestinal bleeding that limited the drug’s effectiveness.

The team noted that treatment with eculizumab started only after multi-organ damage had occurred, suggesting that earlier detection of high-risk TA-TMA could further improve survival rates.

“We were quite excited to see a strong response to this treatment, but the outcomes are not yet ideal,” Jodele says. “Now we hope to determine whether a combination of complement blockers and targeting other endothelial injury pathways may assist those who do not respond to eculizumab alone.”

Treating High-Risk TA-TMA

Graphs showing outcomes for stem cell transplant patients.

Click image to learn more.

A photo of Sonata Jodele.

Sonata Jodele, MD

A photo of Stella Davies, MBBS, PhD.

Stella Davies, MBBS, PhD, MRCP


Jodele S, Dandoy CE, Lane A, Laskin BL, Teusink-Cross A, Myers KC, Wallace G, Nelson A, Bleesing J, Chima RS, Hirsch R, Ryan TD, Benoit S, Mizuno K, Warren M, Davies SM. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. Blood. 2020 Mar 16;135(13):1049-1057.