Fludarabine和Cyclophospamide与骨髓毁损性全身照射联合用于急性髓细胞白血病患者作为异基因造血干细胞移植的预处理方案。欧洲血液和骨髓移植学会急性白血病工作组一项研究。
Fludarabine versus cyclophospamide in combination with myeloablative total body irradiation as conditioning for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
发表日期：2023 Jan 10
作者：
Sebastian Giebel, Myriam Labopin, Thomas Schroeder, Ryszard Swoboda, Johan Maertens, Jean Henri Bourhis, Giovanni Grillo, Urpu Salmenniemi, Inken Hilgendorf, Nicolaus Kröger, Xavier Poiré, Jan J Cornelissen, Mutlu Arat, Bipin Savani, Alexandros Spyridonidis, Arnon Nagler, Mohamad Mohty
来源：
AMERICAN JOURNAL OF HEMATOLOGY
摘要：
全身放射治疗（TBI）剂量为12 Gy，结合环磷酰胺（CyTBI12Gy）是治疗急性髓性白血病（AML）患者进行异基因造血干细胞移植（allo-HCT）的标准造血抑制方案之一。在临床实践中，为减少毒性，环磷酰胺可以被氟达拉滨所替代（FluTBI12Gy）。我们回顾性地比较了在完全缓解状态下接受同体或非亲缘供者allo-HCT治疗的AML患者的CyTBI12Gy组和FluTBI12Gy组的疗效。符合条件的1684名成年患者中，每组分别纳入109名患者进行匹配对分析。2年内复发率在FluTBI12Gy组为25%，在CyTBI12Gy组为28%（p=0.44）。非复发性死亡（NRM）分别为17%和19%（p=0.89）。无白血病生存和总生存率分别为65%和54%（p=0.28），以及70%和60.5%（p=0.17）。FluTBI12Gy组的2-4级急性移植物抗宿主病（GVHD）的累积发生率明显低于CyTBI12Gy组（16% vs 34%，p=0.005），而3-4级急性GVHD和慢性GVHD的发生率没有显著差异。在FluTBI12Gy组和CyTBI12Gy组中，GVHD和复发无病生存的概率分别为49%和41%（p=0.17）。我们得出结论，在CR状态下接受allo-HCT治疗的AML患者中，环磷酰胺可以被氟达拉滨所替代，不会对疗效产生负面影响，而FluTBI12Gy与降低的2-4级急性GVHD发生率和令人鼓舞的生存率相关。 ©2023 Wiley Periodicals LLC.
Total body irradiation (TBI) at a dose of 12 Gy combined with cyclophosphamide (CyTBI12Gy) is one of the standard myeloablative regimens for patients with acute myeloid leukemia (AML) treated with allogeneic hematopoietic cell transplantation (allo-HCT). In clinical practice, cyclophosphamide may be substituted with fludarabine (FluTBI12Gy) to reduce toxicity. We retrospectively compared outcomes of CyTBI12Gy with FluTBI12Gy for patients with AML treated in complete remission (CR) with allo-HCT from either a matched sibling or unrelated donor. Of 1684 adults who met inclusion criteria, 109 patients in each group were included in a matched-pair analysis. The cumulative incidence of relapse at 2 years was 25% in the FluTBI12Gy compared to 28% in the CyTBI12Gy group (p = .44) while non-relapse mortality (NRM) was 17% versus 19%, (p = .89) respectively. The rates of leukemia-free survival and overall survival were 65% versus 54% (p = .28) and 70% versus 60.5% (p = .17). Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was significantly lower for FluTBI12Gy than CyTBI12Gy (16% vs. 34%, p = .005), while the incidences of grade 3-4 acute GVHD and chronic GVHD did not differ significantly. The probability of GVHD and relapse-free survival was 49% in the FluTBI12Gy and 41% in the CyTBI12Gy group (p = .17). We conclude that for patients with AML treated with allo-HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2-4 acute GVHD and encouraging survival rates.© 2023 Wiley Periodicals LLC.