Nasilowska-Adamska Barbara, Czyz Anna, Markiewicz Miroslaw, Rzepecki Piotr, Piatkowska-Jakubas Beata, Paluszewska Monika, Dzierzak-Mietla Monika, Solarska Iwona, Borg Katarzyna, Prochorec-Sobieszek Monika, Szydlo Richard, Lewandowski Krzysztof, Skotnicki Aleksander, Jedrzejczak Wieslaw Wiktor, Kyrcz-Krzemien Slawomira, Komarnicki Mieczyslaw, Warzocha Krzysztof
Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
University of Medical Sciences, Poznan, Poland.
Eur J Haematol. 2016 Mar;96(3):236-44. doi: 10.1111/ejh.12575. Epub 2015 May 18.
Internal tandem duplication (ITD) of the FLT3 gene (Fms-like tyrosine kinase 3) is the most commonly found mutation in acute myeloid leukemia (AML). The significance of FLT3-ITD at diagnosis was retrospectively estimated for allo-HSCT (allogeneic hematopoietic stem cell transplantation) outcomes in 140 patients, median age of 38, undergoing allo-HSCT after myeloablative conditioning in first complete remission of AML. FLT3-ITD was detected at AML diagnosis in 42/140 (30%) of included into this study patients. At 3 years, relapse incidence (RI) following allo-HSCT in AML patients with intermediate or normal karyotype was significantly higher in those FLT3-ITD positive than FLT3-ITD negative [52.9 vs. 20.4%, P = 0.002]. Additionally, patients with mild chronic graft-versus-host disease (cGvHD) had significantly lower RI compared to patients with moderate or severe grade cGvHD or those not experiencing cGvHD, respectively, 4.8 vs. 36.0 vs. 27.8%, P = 0.032. FLT3-ITD was harboring a poor prognosis in AML with intermediate or normal karyotype and significantly increased risk of relapse following allo-HSCT. It appears that allo-HSCT does not cure patients with FLT3-ITD, unless they develop symptoms of mild cGvHD and graft versus leukemia, which may decrease RI.
FLT3基因(Fms样酪氨酸激酶3)的内部串联重复(ITD)是急性髓系白血病(AML)中最常见的突变。回顾性评估了140例年龄中位数为38岁的患者在AML首次完全缓解后接受清髓性预处理后进行异基因造血干细胞移植(allo-HSCT)时,诊断时FLT3-ITD对allo-HSCT结局的意义。在纳入本研究的140例患者中,42例(30%)在AML诊断时检测到FLT3-ITD。3年时,核型为中间型或正常型的AML患者中,FLT3-ITD阳性者allo-HSCT后的复发率(RI)显著高于FLT3-ITD阴性者[52.9%对20.4%,P = 0.002]。此外,轻度慢性移植物抗宿主病(cGvHD)患者的RI显著低于中度或重度cGvHD患者或未发生cGvHD的患者,分别为4.8%对36.0%对27.8%,P = 0.032。FLT3-ITD在核型为中间型或正常型的AML中预后较差,allo-HSCT后复发风险显著增加。似乎allo-HSCT不能治愈FLT3-ITD患者,除非他们出现轻度cGvHD和移植物抗白血病症状,这可能会降低RI。