Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Department of Blood Transfusion, The First Affiliated Hospital of Soochow University, Suzhou, China.
Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):e107-e115. doi: 10.1016/j.clml.2018.11.006. Epub 2018 Nov 12.
FLT3 mutations have been well-studied in acute myeloid leukemia (AML), and the detection of the FLT3 gene has become a clinical routine. However, it has not been fully analyzed in other hematologic malignancies, such as myelodysplastic syndromes (MDS).
Between 2010 and 2016, 304 adult patients with de novo MDS had the FLT3 sequence tested on their bone marrow sample. With 279 patients who had follow-up information, we also analyzed the impact of clinical and laboratory characteristics as well as FLT3 mutation status and treatment on prognosis.
We found that the transformation rate was 3 (42.9%) of 7 patients in the FLT3-ITD-positive group, compared with 31 (10.4%) of 297 among FLT3-ITD-negative patients (P = .033). The median progression-free survival of the FLT3-ITD mutated and wild-type groups were 43 days and 363.5 days, respectively (P < .0001). The median overall survival (OS) of the 2 groups were 218 days and 410.5 days, respectively (P < .0001). We also found that 5 factors had independent prognostic impact on OS: white blood cell counts, bone marrow blast percentage, cytogenetics, transplantation status, and FLT3-ITD mutation. Furthermore, compared with the transformation group, the non-progression group was younger (P = .034), with a lower platelet count (P = .022), a lower bone marrow blast percentage (P = .001), a lower FLT3-ITD incidence (P = .007), and a longer OS (P < .0001).
When observed at the MDS stage, patients harboring FLT3-ITD mutations had higher AML transformation rate, quicker disease progression, and shorter survival than wild-type patients. Nevertheless, once the disease progressed to leukemia, the impact of FLT3-ITD mutations on prognosis was slight. In addition, the prognosis of secondary AML was very poor whether there was an FLT3-ITD mutation or not.
FLT3 基因突变已在急性髓系白血病（AML）中得到充分研究，并且 FLT3 基因的检测已成为临床常规。然而，在其他血液恶性肿瘤（如骨髓增生异常综合征 [MDS]）中尚未得到充分分析。
在 2010 年至 2016 年间，对 304 例初治 MDS 成年患者的骨髓样本进行了 FLT3 序列检测。在有随访信息的 279 例患者中，我们还分析了临床和实验室特征以及 FLT3 突变状态和治疗对预后的影响。
我们发现，FLT3-ITD 阳性组中 7 例（42.9%）患者的转化率为 3 例，而 FLT3-ITD 阴性组中 297 例（10.4%）患者为 31 例（P=0.033）。FLT3-ITD 突变和野生型组的中位无进展生存期分别为 43 天和 363.5 天（P<0.0001）。两组的中位总生存期（OS）分别为 218 天和 410.5 天（P<0.0001）。我们还发现，5 个因素对 OS 有独立的预后影响：白细胞计数、骨髓原始细胞比例、细胞遗传学、移植状态和 FLT3-ITD 突变。此外，与转化组相比，非进展组更年轻（P=0.034），血小板计数更低（P=0.022），骨髓原始细胞比例更低（P=0.001），FLT3-ITD 发生率更低（P=0.007），OS 更长（P<0.0001）。
在 MDS 阶段观察时，携带 FLT3-ITD 突变的患者与野生型患者相比，AML 转化率更高，疾病进展更快，生存期更短。然而，一旦疾病进展为白血病，FLT3-ITD 突变对预后的影响就很小。此外，无论是否存在 FLT3-ITD 突变，继发性 AML 的预后都非常差。
