Time course of organ and hematological response to complement blockage in transplantassociated thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation

Tatiana Rudakova ^* Julia Vlasova Olesya Paina Olga Slesarchuk Marina Gorodnova Tatiana Schegoleva Oleg Goloshchapov Tatiana Bykova Elena Morozova Lyudmila Zubarovskaya Ivan Moiseev Alexander Kulagin

• RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia

Hematopoietic stem cell transplantation (HSCT) offers a potential cure for various hematologic malignancies and non-malignant disorders, but is often accompanied by severe complications, one of the most challenging being transplant-associated thrombotic microangiopathy (TA-TMA). Eculizumab, a complement inhibitor, has emerged as an effective therapeutic option for TA-TMA. The present single-centre retrospective study was conducted at Pavlov University, St. Petersburg, to evaluate the efficacy of eculizumab in fourteen adult and pediatric patients who developed high-risk TA-TMA following HSCT between 2015 and 2023 years. Response to treatment was evaluated by monitoring organ functions, blood counts, transfusion requirements, presence of schistocytes in peripheral blood, and increased serum lactate dehydrogenase (LDH). The primary endpoint was overall survival at one hundred days from eculizumab administration. The secondary endpoints were cumulative incidence of serum lactate dehydrogenase level decrease by 25% and to the limit of the normal range for age from the date of the initiation of eculizumab, cumulative incidence of 50% increase in platelet level or stable platelet level ≥ 20x109/l was 74% (95% CI, 32-92) with median time 21 days (range, 1-104), cumulative incidence of platelet level ≥ 50x109/l, and 1 year from the date of the initiation of eculizumab. Overall survival at one hundred days was 57% (95%CI, 36-90). Cumulative incidence of LDH decrease by 25% was 89% (95% CI, 26-99) with median time of 11 days (range, 2-27). Cumulative incidence of LDH≤1.5 upper reference limits (URL) after eculizumab therapy was 73% (95% CI, 34-91) with median time of 22 days (range, 2-170). Cumulative incidence of 50% increase in platelet level or stable platelet level ≥ 20x109/l was 74% (95% CI, 32-92) with median time 21 days (range, 1-104).Cumulative incidence of platelet level ≥ 50x109/l was 56% (95% CI, 22-80) with median time of platelet increase 75 days (range, 5-384). Complete response was documented in 57% of the group. In summary, eculizumab is a well-tolerated promising therapeutic intervention for TA-TMA, but more studies are needed to establish its timing and dosage regimen in TA-TMA.