Transplant-Associated Thrombotic Microangiopathy After Autologous Hematopoietic Stem Cell Transplantation Treated With Eculizumab

TL;DR

This paper reports the first case of a rare condition called TA-TMA after autologous stem cell transplant in an adult, successfully treated with eculizumab, a complement-targeting drug.

Contribution

First reported case of TA-TMA after autologous HSCT in adults treated with eculizumab.

Findings

TA-TMA after autologous HSCT is extremely rare but can occur in adults.

Eculizumab led to clinical improvement despite serious complications like pulmonary hypertension and right-sided heart failure.

Early diagnosis and complement-targeting therapy may improve outcomes in autologous HSCT-related TA-TMA.

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) generally occurs after allogeneic hematopoietic stem cell transplantation (HSCT) and has a high mortality rate. However, TA-TMA after autologous HSCT is rare. In particular, there are almost no accurate reports of TA-TMA after autologous HSCT in adults. Furthermore, there are no reports of such patients being treated with complement-targeting agents, including eculizumab. We report the first adult case of TA-TMA after autologous HSCT treated with eculizumab. A 66-year-old woman in complete remission after the second relapse of follicular lymphoma received autologous HSCT following the MEAM regimen (ranimustine [MCNU], etoposide, cytarabine [Ara-C], and melphalan). Trilineage engraftment was confirmed. However, she developed new-onset hypertension, hemolytic anemia, thrombocytopenia, and renal failure. The screening results were notable for normal coagulation, normal ADAMTS13 activity and inhibitor levels, and negative direct and indirect Coombs tests. No variants appeared in complement regulatory genes such as CFH, CFB, CFHR5, CFI, CD46, C3, THBD, and DGKE. In addition, all other microbiological and autoimmune screening tests were negative. Based on comprehensive diagnostic findings and the onset within 100 days post-HSCT, TA-TMA was diagnosed. She also developed acute respiratory failure requiring >15 L/min of oxygen. Transthoracic echocardiography revealed pulmonary hypertension (PH) and right-sided heart failure (RHF) as complications of TA-TMA. Following the administration of eculizumab, clinical improvement was observed. In conclusion, TA-TMA after first-time autologous HSCT in adults is extremely rare but can occur. Even with serious complications such as PH and RHF, TA-TMA after autologous HSCT may improve with early diagnosis and prompt initiation of complement-targeting agents, such as eculizumab. These findings suggest that complement inhibition may play a critical therapeutic role even in patients with cardiopulmonary complications and raise the possibility that the prognosis of TA-TMA after autologous HSCT may be more favorable than previously reported in allogeneic HSCT, with a lower mortality rate.

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