背景:小儿急性髓细胞性白血病(AML)的髓外浸润(EMI)结果存在争议,对于干细胞移植(SCT)和吉妥珠单抗(GO)治疗对EMI患者的影响知之甚少。
方法:我们从产生有效治疗的治疗应用研究(TARGET)数据集中检索了713例儿童AML患者的临床数据,并分析了EMI患者在诊断和复发时的临床和预后特征。
结果:共有123例患者在诊断时被确定为患有EMI,64例患者在复发时出现EMI。EMI的存在与年龄≤2岁有关,M5形态,异常核型,和KMT2A重新安排。在复发的EMI患者中,高白细胞增多和复杂核型更为普遍。此外,诊断为EMI的患者FLT3ITD-/NPM1+的发生率降低,而那些在复发时患有EMI的患者显示FLT3ITD+的频率较低。诊断为EMI的患者在诱导过程1结束时表现出较低的完全缓解(CR)率和较高的复发率。重要的是,诊断时的EMI独立地预测了较短的无事件生存期(EFS)和总生存期(OS)。关于复发患者,复发时发生EMI对OS无影响.然而,与患有CNS/无MS的患者相比,患有髓样肉瘤(MS)/无中枢神经系统(CNS)的复发患者的OS较差。此外,关于EMI患者在诊断时,SCT未能提高生存率,而GO治疗可能会增强OS。
结论:诊断时的EMI是小儿AML的独立不良预后危险因素,GO治疗有可能提高诊断时EMI患者的生存率。
BACKGROUND: The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and
gemtuzumab ozogamicin (GO) treatment on patients with EMI.
METHODS: We retrieved the clinical data of 713 pediatric patients with AML from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, and analyzed the clinical and prognostic characteristics of patients with EMI at diagnosis and relapse.
RESULTS: A total of 123 patients were identified to have EMI at diagnosis and 64 presented with EMI at relapse. The presence of EMI was associated with age ≤2 years, M5 morphology, abnormal karyotype, and KMT2A rearrangements. Hyperleukocytosis and complex karyotype were more prevalent in patients with EMI at relapse. Additionally, patients with EMI at diagnosis had a reduced incidence of FLT3 ITD-/NPM1+, whereas those with EMI at relapse displayed a lower frequency of FLT3 ITD+. Patients with EMI at diagnosis exhibited a lower complete remission (CR) rate at the end of Induction Course 1 and higher relapse incidence. Importantly, EMI at diagnosis independently predicted both shorter event-free survival (EFS) and overall survival (OS). Regarding relapse patients, the occurrence of EMI at relapse showed no impact on OS. However, relapse patients with myeloid sarcoma (MS)/no central nervous system (CNS) exhibited poorer OS compared to those with CNS/no MS. Furthermore, regarding patients with EMI at diagnosis, SCT failed to improve the survival, whereas GO treatment potentially enhanced OS.
CONCLUSIONS: EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.