氟达拉滨联合2 Gy全身照射或抗胸腺细胞球蛋白联合8 Gy胸腺照射后的非清髓性异基因造血细胞移植：比利时血液学会的一项II期随机研究
Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society.
作者信息
Baron Frédéric, Zachée Pierre, Maertens Johan, Kerre Tessa, Ory Aurélie, Seidel Laurence, Graux Carlos, Lewalle Philippe, Van Gelder Michel, Theunissen Koen, Willems Evelyne, Emonds Marie-Paule, De Becker Ann, Beguin Yves
机构信息
Department of Hematology, University of Liège, and CHU of Liège, Sart-Tilman, 4000, Liège, Belgium.
ZNA Stuivenberg, Antwerpen, Belgium.
出版信息
J Hematol Oncol. 2015 Feb 6;8:4. doi: 10.1186/s13045-014-0098-9.
BACKGROUND
Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT).
METHODS
Here, we report the results of a phase II multicenter randomized study comparing non-myeloablative allo-HCT from HLA-identical siblings (n = 54) or from 10/10 HLA-matched unrelated donors (n = 40) with either fludarabine plus 2 Gy total body irradiation (Flu-TBI arm; n = 49) or 8 Gy TLI + anti-thymocyte globulin (TLI-ATG arm; n = 45) conditioning.
RESULTS
The 180-day cumulative incidences of grade II-IV acute GVHD (primary endpoint) were 12.2% versus 8.9% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Two-year cumulative incidences of moderate/severe chronic GVHD were 40.8% versus 17.8% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Five Flu-TBI patients and 10 TLI-ATG patients received pre-emptive DLI for low donor chimerism levels, while 1 Flu-TBI patient and 5 TLI-ATG patients (including 2 patients given prior pre-emptive DLIs) received a second HCT for poor graft function, graft rejection, or disease progression. Four-year cumulative incidences of relapse/progression were 22% and 50% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Four-year cumulative incidences of nonrelapse mortality were 24% and 13% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Finally, 4-year overall (OS) and progression-free survivals (PFS) were 53% and 54%, respectively, in the Flu-TBI arm, versus 54% (P = 0.9) and 37% (P = 0.12), respectively, in the TLI-ATG arm.
CONCLUSIONS
In comparison to patients included in the Flu-TBI arm, patients included in the TLI-ATG arm had lower incidence of chronic GVHD, higher incidence of relapse and similar OS.
TRIAL REGISTRATION
The study was registered on ClinicalTrial.gov ( NCT00603954 ) and EUDRACT (2010-024297-19) .
背景
迄今为止，很少有研究对异基因造血细胞移植（allo-HCT）的不同非清髓性预处理方案进行直接比较。
方法
在此，我们报告一项II期多中心随机研究的结果，该研究比较了来自 HLA 相同同胞（n = 54）或 10/10 HLA 匹配无关供者（n = 40）的非清髓性 allo-HCT，预处理方案为氟达拉滨加 2 Gy 全身照射（氟达拉滨-全身照射组；n = 49）或 8 Gy 胸腺照射+抗胸腺细胞球蛋白（胸腺照射-抗胸腺细胞球蛋白组；n = 45）。
结果
II-IV 级急性移植物抗宿主病（GVHD）的 180 天累积发生率（主要终点）在氟达拉滨-全身照射组和胸腺照射-抗胸腺细胞球蛋白组患者中分别为 12.2%和 8.9%（P = 0.5）。中度/重度慢性 GVHD 的两年累积发生率在氟达拉滨-全身照射组和胸腺照射-抗胸腺细胞球蛋白组患者中分别为 40.8%和 17.8%（P = 0.017）。5 例氟达拉滨-全身照射组患者和 10 例胸腺照射-抗胸腺细胞球蛋白组患者因供体嵌合水平低接受了抢先性供体淋巴细胞输注（DLI），而 1 例氟达拉滨-全身照射组患者和 5 例胸腺照射-抗胸腺细胞球蛋白组患者（包括 2 例先前接受过抢先性 DLI 的患者）因移植物功能不良、移植物排斥或疾病进展接受了第二次 HCT。复发/进展的四年累积发生率在氟达拉滨-全身照射组和胸腺照射-抗胸腺细胞球蛋白组患者中分别为 22%和 50%（P = 0.017）。非复发死亡率的四年累积发生率在氟达拉滨-全身照射组和胸腺照射-抗胸腺细胞球蛋白组患者中分别为 24%和 13%（P = 0.5）。最后，氟达拉滨-全身照射组的 4 年总生存率（OS）和无进展生存率（PFS）分别为 53%和 54%，而胸腺照射-抗胸腺细胞球蛋白组分别为 54%（P = 0.9）和 37%（P = 0.12）。
结论
与氟达拉滨-全身照射组患者相比，胸腺照射-抗胸腺细胞球蛋白组患者的慢性 GVHD 发生率较低，复发率较高，OS 相似。
试验注册
该研究已在 ClinicalTrial.gov（NCT00603954）和 EUDRACT（2010-024297-19）注册。
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