Salama Maram, Ahmed Sonia, Soliman Sonya, El-Sharkawy Nahla, Salem Sherine, El-Nashar Amr, Khedr Reham, Lehmann Leslie, Sidhom Iman, El-Haddad Alaa
Pediatric Oncology Department, Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.
Pediatric Oncology Department, National Cancer Institute Cairo University and Children's Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.
Front Oncol. 2022 Jul 7;12:941885. doi: 10.3389/fonc.2022.941885. eCollection 2022.
Mixed-phenotype acute leukemia (MPAL) in children is an uncommon subtype of acute leukemia that cannot be definitively assigned to a specific lineage. There is no consensus on the best approach to therapy. Management is more complex in low-middle-income countries (LMICs).
To evaluate the clinicopathological characteristics and outcomes of patients with MPAL in a developing country.
A retrospective descriptive study of 42 pediatric patients newly diagnosed with MPAL from July 2007 until December 2017.
The immunophenotyping was T/Myeloid in 24 patients (57.1%) and B/Myeloid in 16 (38.1%). Three subjects had gene rearrangement, two had chromosomes, and eight had internal tandem duplication (FLT3-ITD) with a ratio >0.4. Two subjects died before starting chemotherapy. Ten patients (25%) received acute lymphoblastic leukemia (ALL) induction, and all achieved complete remission (CR) with no induction deaths and no shift of therapy. Thirty patients (75%) started therapy with acute myeloid leukemia (AML) induction: five (16.6%) died during induction, 17 (56.7%) achieved CR, and 10 patients received maintenance ALL therapy after ending AML treatment. Four of the eight patients with induction failure were switched to ALL therapy. The 5-year event-free survival (EFS) and overall survival (OS) rates were 56.7% [standard error (SE): 8.1%] and 61% (SE: 8%), while the cumulative incidence of relapse was 21.7% (SE: 6.7%), with a median follow-up duration of 5.8 years. Patients treated with ALL-directed therapy had a 5-year EFS rate of 111 70% (SE: 14%) and OS rate of 78.8% (SE: 13%). Patients treated with ALL-directed therapy had a 5-year EFS rate of 70% (SE: 14.5%) and OS rate of 78.8% (SE: 13%). mutation showed a significantly lower 5-year EFS rate of 28.6% (SE: 17%) vs. 75% (SE: 9%) for the wild type, p = 0.032. Undernourished patients with a body mass index (BMI) -score ≤-2 at presentation had a significantly lower 5-year EFS rate of 20% (SE: 17%) compared to 61.8% (SE: 8%) for patients with BMI -score >-2, p = 0.015.
This study supports ALL-directed therapy for pediatric MPAL in a setting of LMIC. Given the poor outcome of , the role of inhibitor needs to be explored in this subset of cases.
儿童混合表型急性白血病（MPAL）是急性白血病中一种不常见的亚型，无法明确归为特定谱系。对于最佳治疗方法尚无共识。在低收入和中等收入国家（LMICs），管理更为复杂。
评估发展中国家MPAL患者的临床病理特征和预后。
对2007年7月至2017年12月新诊断的42例儿童MPAL患者进行回顾性描述性研究。
免疫表型为T/髓系的患者有24例（57.1%），B/髓系的有16例（38.1%）。3例患者有基因重排，2例有染色体异常，8例有内部串联重复（FLT3-ITD），比例>0.4。2例患者在开始化疗前死亡。10例患者（25%）接受急性淋巴细胞白血病（ALL）诱导治疗，均获得完全缓解（CR），无诱导死亡且未改变治疗方案。30例患者（75%）开始接受急性髓系白血病（AML）诱导治疗：5例（16.6%）在诱导治疗期间死亡，17例（56.7%）获得CR，10例患者在AML治疗结束后接受ALL维持治疗。8例诱导治疗失败的患者中有4例改为ALL治疗。5年无事件生存率（EFS）和总生存率（OS）分别为56.7%[标准误（SE）：8.1%]和61%（SE：8%），而累积复发率为21.7%（SE：6.7%），中位随访时间为5.8年。接受ALL导向治疗的患者5年EFS率为70%（SE：14.5%），OS率为78.8%（SE：13%）。 突变型患者的5年EFS率显著低于野生型，分别为28.6%（SE：17%）和75%（SE：9%），p = 0.032。就诊时体重指数（BMI）评分≤-2的营养不良患者5年EFS率显著低于BMI评分>-2的患者，分别为20%（SE：17%）和61.8%（SE：8%），p = 0.015。
本研究支持在LMIC环境下对儿童MPAL采用ALL导向治疗。鉴于 的不良预后，需要在这部分病例中探索 抑制剂的作用。
