University of Cincinnati and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisc.
J Allergy Clin Immunol. 2022 Mar;149(3):1097-1104.e2. doi: 10.1016/j.jaci.2021.07.031. Epub 2021 Aug 8.
Allogeneic hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis (HLH) disorders is associated with substantial morbidity and mortality.
The effect of conditioning regimen groups of varying intensity on outcomes after transplantation was examined to identify an optimal regimen or regimens for HLH disorders.
We studied 261 patients with HLH disorders transplanted between 2005 and 2018. Risk factors for transplantation outcomes by conditioning regimen groups were studied by Cox regression models.
Four regimen groups were studied: (1) fludarabine (Flu) and melphalan (Mel) in 123 subjects; (2) Flu, Mel, and thiotepa (TT) in 28 subjects; (3) Flu and busulfan (Bu) in 14 subjects; and (4) Bu and cyclophosphamide (Cy) in 96 subjects. The day 100 incidence of veno-occlusive disease was lower with Flu/Mel (4%) and Flu/Mel/TT (0%) compared to Flu/Bu (14%) and Bu/Cy (22%) (P < .001). The 6-month incidence of viral infections was highest after Flu/Mel (72%) and Flu/Mel/TT (64%) compared to Flu/Bu (39%) and Bu/Cy (38%) (P < .001). Five-year event-free survival (alive and engrafted without additional cell product administration) was lower with Flu/Mel (44%) compared to Flu/Mel/TT (70%), Flu/Bu (79%), and Bu/Cy (61%) (P = .002). The corresponding 5-year overall survival values were 68%, 75%, 86%, and 64%, and did not differ by conditioning regimen (P = .19). Low event-free survival with Flu/Mel is attributed to high graft failure (42%) compared to Flu/Mel/TT (15%), Flu/Bu (7%), and Bu/Cy (18%) (P < .001).
Given the high rate of graft failure with Flu/Mel and the high rate of veno-occlusive disease with Bu/Cy and Flu/Bu, Flu/Mel/TT may be preferred for HLH disorders. Prospective studies are warranted.
异基因造血细胞移植治疗噬血细胞性淋巴组织细胞增生症（HLH）相关疾病与较高的发病率和死亡率相关。
本研究旨在探讨不同强度的预处理方案对移植后结局的影响，以确定 HLH 相关疾病的最佳预处理方案或方案组合。
我们研究了 2005 年至 2018 年间接受移植的 261 例 HLH 相关疾病患者。通过 Cox 回归模型研究了不同预处理方案组的移植结局相关风险因素。
本研究共分为 4 个预处理方案组：（1）氟达拉滨（Flu）+美法仑（Mel）组，共 123 例；（2）Flu+Mel+噻替哌（TT）组，共 28 例；（3）Flu+白消安（Bu）组，共 14 例；（4）Bu+环磷酰胺（Cy）组，共 96 例。与 Flu/Bu（14%）和 Bu/Cy（22%）相比，Flu/Mel（4%）和 Flu/Mel/TT（0%）组患者第 100 天静脉闭塞性疾病的发生率较低（P<.001）。与 Flu/Bu（39%）和 Bu/Cy（38%）相比，Flu/Mel（72%）和 Flu/Mel/TT（64%）组患者 6 个月时病毒感染的发生率更高（P<.001）。无事件生存（无移植物抗宿主病且无需额外细胞产品输注）方面，与 Flu/Mel/TT（70%）、Flu/Bu（79%）和 Bu/Cy（61%）相比，Flu/Mel 组（44%）的 5 年无事件生存率较低（P=.002）。相应的 5 年总生存率分别为 68%、75%、86%和 64%，与预处理方案无关（P=.19）。Flu/Mel 组的无事件生存率较低，主要是由于该组患者的移植物失败率较高（42%），而 Flu/Mel/TT（15%）、Flu/Bu（7%）和 Bu/Cy（18%）组的移植物失败率较低（P<.001）。
鉴于 Flu/Mel 方案的移植物失败率较高，而 Bu/Cy 和 Flu/Bu 方案的静脉闭塞性疾病发生率较高，Flu/Mel/TT 可能是 HLH 相关疾病的首选方案。有必要开展前瞻性研究。
