Tokura Taichiro, Imai Youhei, Saga Reina, Hidai Hiroko, Motomura Sayuri
Hematology, Tokyo Metropolitan Tama-Hokubu Medical Center, Tokyo, JPN.
Hematology, Nippon Medical School, Tokyo, JPN.
Cureus. 2025 Jul 25;17(7):e88785. doi: 10.7759/cureus.88785. eCollection 2025 Jul.
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 , , , , , , , and . 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.
移植相关血栓性微血管病（TA-TMA）通常发生在异基因造血干细胞移植（HSCT）后，死亡率很高。然而，自体HSCT后发生TA-TMA的情况很少见。特别是，几乎没有关于成人自体HSCT后TA-TMA的准确报道。此外，也没有关于此类患者接受包括依库珠单抗在内的补体靶向药物治疗的报道。我们报告了首例接受依库珠单抗治疗的成人自体HSCT后发生TA-TMA的病例。一名66岁女性在滤泡性淋巴瘤第二次复发后完全缓解，按照MEAM方案（司莫司汀[MCNU]、依托泊苷、阿糖胞苷[Ara-C]和美法仑）接受了自体HSCT。确认了三系造血重建。然而，她出现了新发高血压、溶血性贫血、血小板减少和肾衰竭。筛查结果显示凝血功能正常、ADAMTS13活性和抑制剂水平正常、直接和间接抗人球蛋白试验均为阴性。补体调节基因如 、 、 、 、 、 、 、 未出现变异。此外，所有其他微生物学和自身免疫筛查试验均为阴性。根据综合诊断结果以及HSCT后100天内发病，诊断为TA-TMA。她还出现了需要吸氧>15L/分钟的急性呼吸衰竭。经胸超声心动图显示肺动脉高压（PH）和右心衰竭（RHF）是TA-TMA的并发症。给予依库珠单抗后，观察到临床症状改善。总之，成人首次自体HSCT后发生TA-TMA极为罕见，但有可能发生。即使伴有PH和RHF等严重并发症，自体HSCT后TA-TMA通过早期诊断和及时启动补体靶向药物（如依库珠单抗）可能会改善。这些发现表明，补体抑制即使在伴有心肺并发症的患者中也可能发挥关键的治疗作用，并提高了自体HSCT后TA-TMA的预后可能比先前报道的异基因HSCT更有利、死亡率更低的可能性。
