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JCO:来那度胺和阿扎胞苷组合:干细胞移植后急性髓细胞白血病复发患者的新型抢救疗法

2019-01-19 海北 MedSci原创

至今为止,同种异体干细胞移植(allo-SCT)治疗急性髓性白血病(AML)和骨髓增生异常(MDS)后复发患者的抢救选择仍然有限,临床急需新的治疗策略。

至今为止,同种异体干细胞移植(allo-SCT)治疗急性髓性白血病(AML)和骨髓增生异常(MDS)后复发患者的抢救选择仍然有限,临床急需新的治疗策略。

来那度胺(LEN)和阿扎胞苷(AZA)在AML中具有显着的抗肿瘤活性。移植后LEN的施用与移植物抗宿主病(GVHD)相关,但已有的研究显示,AZA在小鼠移植模型中可以改善GVHD。

因此,研究人员检查了LEN / AZA联合给药在移植后复发患者中的耐受性和活性。

allo-SCT治疗AML(n = 24)或MDS(n = 5)后复发的29例患者接受连续AZA(75 mg / m2,连续7天)治疗,随后在第10至30天逐步增加LEN剂量。剂量分配和最大耐受剂量(MTD)估计由改进的贝叶斯连续重评估方法(CRM)指导。

结果显示,顺序AZA和LEN治疗耐受性良好。将移植后LEN与AZA组合的MTD测定为每天25mg。 3名患者发展为2至4级GVHD。没有与GVHD相关的死亡率。 15例(47%)患者中有7例在LEN / AZA治疗后获得了重要的临床反应。 CD8+ T细胞在复发时表现出干扰素-γ/肿瘤坏死因子-α产生受损,在LEN / AZA给药期间没有逆转。

因此,研究人员得出结论,LEN可以在同种异体移植后与AZA一起安全施用,并且这种组合证实了治疗复发的AML / MDS的临床活性,而没有逆转T细胞衰竭的生物学特征。使用CRM模型提高了MTD评估的效率,并提供了额外的灵活性。联合LEN / AZA疗法代表了同种异体移植后复发患者的一种新型和主动的抢救疗法。

 

 

原始出处:

Craddock C et al. Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia. JCO, 2019; doi: 10.1200/JCO.18.00889.

 

本文系梅斯医学(MedSci)原创编译整理,转载需授权!

 

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    2019-08-15 lidong40
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    2019-01-21 chengjn
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    2019-01-21 zhaojie88

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