Division of Hematology/Oncology/BMT, Sheffield Childrens NHS Foundation Trust, Sheffield, UK.
Division of Hematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Pediatr Blood Cancer. 2020 Sep;67(9):e28477. doi: 10.1002/pbc.28477.
Hemophagocytic lymphohistiocytosis (HLH), a rare hyperinflammatory immuneregulatory disorder, is a challenge in hematopoietic stem cell transplantation (HSCT) because of the high rate of mixed chimerism, relapse, and graft failure (GF) unless intensive myeloablative regimens are used. However, historically conventional myeloablative regimens (conv MA) are associated with high toxicity and mortality.
We retrospectively compared transplant outcomes between three preparative regimens of varying intensities: Conv MA (n = 15), reduced-intensity conditioning (RIC, n = 12), and a treosulfan-based reduced-toxicity conditioning (RTC, n = 9).
Patients in the RIC cohort had a higher incidence of mixed donor chimerism and five patients (42%) developed secondary GF (P = .002) compared to the other two regimens. There was a higher incidence of veno-occlusive disease and intensive care unit (ICU) admissions in the Conv MA cohort. With the RTC regimen, there was a similar 2-year overall survival (89, 73, and 83%; P = .87), but improved compound EFS (lack of relapse, GF, second transplant or additional donor cell infusions, or death; 89, 73, and 42%, P = .041) in RTC, Conv MA, and RIC regimen, respectively.
The intensity of the preparative regimen has a significant impact on outcome of HSCT for HLH. The newly described treosulfan-based RTC provides for a stable graft with a reasonable toxicity profile.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的过度炎症性免疫调节紊乱，由于混合嵌合率高、复发和移植物衰竭（GF），在造血干细胞移植（HSCT）中是一个挑战，除非使用强化的清髓性方案。然而，传统的清髓性方案（conv MA）在历史上与高毒性和高死亡率相关。
我们回顾性地比较了三种不同强度的预处理方案的移植结果：传统清髓性方案（conv MA，n=15）、减低强度预处理（RIC，n=12）和基于三嗪的减低毒性预处理（RTC，n=9）。
RIC 组患者混合供者嵌合的发生率更高，5 名患者（42%）发生继发性 GF（P=0.002），与其他两种方案相比。Conv MA 组患者静脉闭塞性疾病和重症监护病房（ICU）入院率更高。采用 RTC 方案，2 年总生存率相似（89%、73%和 83%；P=0.87），但 RTC、Conv MA 和 RIC 方案的复合 EFS（无复发、GF、二次移植或额外供者细胞输注或死亡）分别提高（89%、73%和 42%，P=0.041）。
预处理方案的强度对 HLH 的 HSCT 结果有显著影响。新描述的基于三嗪的 RTC 提供了一种具有合理毒性特征的稳定移植物。
