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约旦急性髓系白血病患者中 FLT3 激活突变的分析:与 FAB 亚型的关联及预后不良亚组的鉴定。

Analysis of FLT3-Activating Mutations in Patients With Acute Myelogenous Leukemia in Jordan: Association With FAB Subtypes and Identification of Subgroups With Poor Prognosis.

机构信息

Department of Medical Oncology-Hematology, Bone Marrow Transplantation, King Hussein Cancer Center, Amman, Jordan.

Biostatistics Unit, Research Office, King Hussein Cancer Center, Amman, Jordan.

出版信息

Clin Lymphoma Myeloma Leuk. 2021 Jul;21(7):e588-e597. doi: 10.1016/j.clml.2021.02.006. Epub 2021 Mar 9.

DOI:10.1016/j.clml.2021.02.006
PMID:33811005
Abstract

BACKGROUND

FLT3 mutations are common in acute myeloid leukemia (AML), particularly in French-American-British M2 subtype AML and in cytogenetically normal (CN) AML; however, its incidence in Jordan is poorly studied. An FLT3 mutation implies poor prognosis in AML patients. We aimed to assess the incidence and prognostic value of FLT3 mutations in AML in Jordan.

PATIENTS AND METHODS

One hundred thirty-two newly diagnosed unselected AML patients were included. Patient data were collected, including demographics as well as morphologic, cytogenetic, and molecular testing results. FLT3 mutations were detected by real-time reverse transcriptase PCR, next-generation sequencing, or both. Survival analysis and comparisons of incidence, remission rate, relapse, and survival outcomes between FLT3-mutated and wild-type groups were done and prognostic factors identified.

RESULTS

FLT3 mutation was detected in 40% of AML patients. The highest incidence was associated with M2 subtype AML (47%) and CN-AML (50%). There was a significant negative association between FLT3 mutations and overall survival (OS), as well as a trend toward improved relapse-free survival, with 3-year OS being 19.17% vs 34.16% (P < .0001) and 33.6% vs 71.0% (P = .085), respectively. Patients with FLT3 mutation had a significantly better complete remission rate after induction (67.9% vs 63.3%, P = .001). Also, OS improved in patients with complete remission (P = .0015) and who then continued to allogeneic hematopoietic cell transplantation compared to FLT3 wild-type patients (P < .001).

CONCLUSION

FLT3 mutation is common in Jordanian AML patients, with the highest incidence occurring in patients with M2 or CN disease. It implies a poor prognosis, with poor OS and relapse-free survival, which may be abrogated by early allogeneic transplantation and/or peritransplantation provision of FLT3 inhibitors.

摘要

背景

FLT3 突变在急性髓系白血病(AML)中很常见,尤其是在法裔美国-英国(FAB)M2 亚型 AML 和细胞遗传学正常(CN)AML 中;然而,在约旦,其发病率研究甚少。FLT3 突变意味着 AML 患者的预后不良。我们旨在评估 FLT3 突变在约旦 AML 中的发生率和预后价值。

患者和方法

纳入了 132 例新诊断的未选择的 AML 患者。收集了患者数据,包括人口统计学数据以及形态学、细胞遗传学和分子检测结果。通过实时逆转录酶 PCR、下一代测序或两者结合检测 FLT3 突变。进行了 FLT3 突变组和野生型组之间的生存分析以及发病率、缓解率、复发和生存结果的比较,并确定了预后因素。

结果

AML 患者中有 40%检测到 FLT3 突变。最高的发生率与 M2 亚型 AML(47%)和 CN-AML(50%)相关。FLT3 突变与总生存期(OS)显著负相关,并且无复发生存期有改善趋势,3 年 OS 分别为 19.17%和 34.16%(P<0.0001)和 33.6%和 71.0%(P=0.085)。诱导后 FLT3 突变患者完全缓解率显著更高(67.9%和 63.3%,P=0.001)。此外,在获得完全缓解的患者中 OS 改善(P=0.0015),与 FLT3 野生型患者相比,随后继续进行异基因造血细胞移植的患者 OS 改善(P<0.001)。

结论

FLT3 突变在约旦 AML 患者中很常见,M2 或 CN 疾病患者的发生率最高。它意味着预后不良,OS 和无复发生存期差,但通过早期异基因移植和/或移植前提供 FLT3 抑制剂可能会改善。

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