Metzelder S K, Wollmer E, Neubauer A, Burchert A
Klinik für Hämatologie, Onkologie und Immunologie, Philipps-Universität Marburg, Universitätsklinikum Gießen und Marburg, Standort Marburg.
Dtsch Med Wochenschr. 2010 Sep;135(38):1852-6. doi: 10.1055/s-0030-1247870. Epub 2010 Aug 25.
The therapeutic options for relapsed or refractory FLT3-ITD positive AML are limited, particularly in case of a prior allogenic stem cell transplantation (SCT) or poor performance status. The clinical value of a targeted intervention using the FLT3-ITD-specific inhibitor sorafenib in this situation is largely unknown.
Between 2007 and 2010 eight patients (4 men, 4 women; age 40-75 years) with relapsed or refractory FLT3-ITD positive acute myeloid leukemia (AML) before (n=4) and after allogenic SCT (n=5) were treated off-label with sorafenib.
All patients showed rapid hematological responses. There were three complete molecular remissions when sorafenib was given after allogenic SCT. Two of them are ongoing for 12 and 15 months, respectively. Long-term remissions after prior allogenic SCT were associated with the re-establishment of a chronic graft versus host reaction. Side effects could be controlled by dose reduction.
Sorafenib is apparently an effective treatment alternative for patients with relapsed or refractory FLT3-ITD positive AML. In the context of a prior allogenic SCT it may have curative potential via inducing a synergism between targeted inhibition of FLT3-ITD and anti-leukemic immunity.
复发或难治性FLT3-ITD阳性急性髓系白血病（AML）的治疗选择有限，尤其是在既往接受过异基因干细胞移植（SCT）或体能状态较差的情况下。在这种情况下，使用FLT3-ITD特异性抑制剂索拉非尼进行靶向干预的临床价值很大程度上未知。
2007年至2010年期间，8例（4例男性，4例女性；年龄40 - 75岁）复发或难治性FLT3-ITD阳性急性髓系白血病患者在异基因SCT前（n = 4）和后（n = 5）接受了索拉非尼的非标签治疗。
所有患者均表现出快速的血液学反应。异基因SCT后给予索拉非尼时出现了3例完全分子缓解。其中2例分别持续了12个月和15个月。既往异基因SCT后的长期缓解与慢性移植物抗宿主反应的重新建立有关。副作用可通过降低剂量来控制。
索拉非尼显然是复发或难治性FLT3-ITD阳性AML患者的一种有效治疗选择。在既往异基因SCT的背景下，它可能通过诱导FLT3-ITD的靶向抑制与抗白血病免疫之间的协同作用而具有治愈潜力。
