Department of Stem Cell Transplantation, St. Anna Children's Hospital, Medical University of Vienna, Kinderspitalgasse 6, 1090, Vienna, Austria.
EBMT Statistical Unit, Pediatric Diseases Working Party, Paris, France.
Ann Hematol. 2022 Mar;101(3):655-665. doi: 10.1007/s00277-021-04732-4. Epub 2022 Jan 9.
Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients' life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan-fludarabine-based and treosulfan-fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan-fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan-fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3-95.1%) after busulfan-fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7-96.6%) after treosulfan-fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.
支持治疗在输血依赖型地中海贫血（TDT）患者中的显著进展提高了患者的预期寿命。然而，输血相关的铁过载仍然是长期生存和良好生活质量的一个重大障碍。目前，异基因造血干细胞移植（HSCT）是当前的治疗标准。除了选择最佳的供体外，优化预处理方案对于接受 HSCT 的 TDT 患者的治疗结果至关重要。本回顾性分析的目的是研究以白消安-氟达拉滨和替莫唑胺-氟达拉滨为基础的预处理在 TDT 患者 HSCT 中的作用。我们纳入了 2010 年至 2018 年间在欧洲血液和骨髓移植学会（EBMT）数据库中接受首次 HSCT 的 772 名患者。410 名患者接受了以白消安-氟达拉滨为基础的预处理（中位年龄 8.6 岁），362 名患者接受了以替莫唑胺-氟达拉滨为基础的预处理（中位年龄 5.7 岁）。通过预处理方案回顾性比较患者的结局。白消安-氟达拉滨预处理后 2 年总生存率为 92.7%（95%置信区间：89.3-95.1%），替莫唑胺-氟达拉滨预处理后为 94.7%（95%置信区间：91.7-96.6%）。总体上第二次 HSCT 的发生率非常低。死亡的主要原因是感染、移植物抗宿主病和排斥反应。总之，在接受 HSCT 的 TDT 患者中，以白消安或替莫唑胺为基础的清髓性预处理可获得相似的高治愈率。需要进行长期随访研究来解决器官毒性和性腺功能的重要问题。
