Rasekh Eman O, Elsayed Ghada M, Madney Youssef, El Gammal Mosaad M
Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Pediatric Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Clin Lymphoma Myeloma Leuk. 2020 Mar;20(3):156-167. doi: 10.1016/j.clml.2019.08.006. Epub 2019 Sep 18.
Acute promyelocytic leukemia (APL) has a characteristic peculiar morphologic and genetic features as well as a more favorable outcome. We studied the differential effect of bcr-1 and bcr-3 isoforms of the promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) transcript together with FLT3 internal tandem duplication (FLT3-ITD) mutation status on the outcome of newly diagnosed de novo APL patients.
This cohort study included all patients diagnosed with APL at outpatient medical and pediatric oncology clinics of the National Cancer Institute, Cairo University, Cairo, Egypt, from May 2012 to January 2018.
The study included 118 patients with APL, 71 adults (60.2%) and 47 children (39.8%). Median (range) age was 25 (1.5-70) years. Children had significantly higher total leukocyte count (≥10 × 10/L), disseminated intravascular coagulation (DIC), and thrombocytopenia (< 40 × 10/L) than adults (P = .04, .03, and .04, respectively), while the latter group had significantly higher hemorrhage than children (P = .04). FLT3-ITD mutation was detected in the whole group, children, and adults in 23.7%, 30.6%, and 24.6%, respectively. FLT3-ITD mutation was significantly associated with leukocytosis in the whole group (P = .039). bcr-3 was significantly associated with FLT3-ITD mutation in the whole APL cohort and in adults (P = .011, P = .022). All children (both bcr-1 and bcr-3) and all adult patients with bcr-3 experienced CR, while 22 (78.5%) of 28 patients with bcr-1 experienced CR (P = .04). APL patients with DIC and hemorrhage had significantly lower overall survival (P = .002 and < .001, respectively). Overall survival for APL in children was significantly better than in adults (P = .005). Multivariate analysis indicated that age was an independent prognostic variable affecting survival (hazard ratio = 2.6; 95% confidence interval, 1.3-5.3; P = .007) (adults had hazard ratio of death 2.6 times higher than children). DIC and FLT3-ITD were independent prognostic variables affecting survival in children with APL (hazard ratio = 12.3; 95% confidence interval, 1.46-104.61; P = .021; and hazard ratio = 5.2; 95% confidence interval, 1.01-26.95; P = .048, respectively).
Age is an independent prognostic factor for APL. bcr-3 is significantly associated with FLT3-ITD in adults with APL. DIC and FLT3-ITD are adverse prognostic factors in children with APL. Despite children being at higher risk, outcome is better than in adults.
急性早幼粒细胞白血病（APL）具有独特的形态学和遗传学特征，且预后相对较好。我们研究了早幼粒细胞白血病/维甲酸受体α（PML-RARA）转录本的bcr-1和bcr-3亚型以及FLT3内部串联重复（FLT3-ITD）突变状态对新诊断的初发APL患者预后的不同影响。
本队列研究纳入了2012年5月至2018年1月在埃及开罗开罗大学国家癌症研究所门诊医学和儿科肿瘤诊所诊断为APL的所有患者。
该研究纳入了118例APL患者，其中71例为成人（60.2%），47例为儿童（39.8%）。中位（范围）年龄为25（1.5 - 70）岁。儿童的白细胞总数（≥10×10⁹/L）、弥散性血管内凝血（DIC）和血小板减少症（<40×10⁹/L）显著高于成人（分别为P = 0.04、0.03和0.04），而成年组的出血情况显著高于儿童（P = 0.04）。在整个研究组、儿童组和成人组中，FLT3-ITD突变的检出率分别为23.7%、30.6%和24.6%。FLT3-ITD突变在整个研究组中与白细胞增多显著相关（P = 0.039）。在整个APL队列以及成人中，bcr-3与FLT3-ITD突变显著相关（P = 0.011，P = 0.022）。所有儿童（bcr-1和bcr-3亚型）以及所有携带bcr-3的成年患者均实现完全缓解（CR），而28例携带bcr-¹的患者中有22例（78.5%）实现CR（P = 0.04）。发生DIC和出血的APL患者总生存期显著较低（分别为P = 0.002和<0.001）。儿童APL患者的总生存期显著优于成人（P = 0.005）。多因素分析表明，年龄是影响生存的独立预后变量（风险比=2.6；95%置信区间，1.3 - 5.3；P = 0.007）（成人的死亡风险比是儿童的2.6倍）。DIC和FLT3-ITD是影响儿童APL患者生存的独立预后变量（风险比分别为=12.3；95%置信区间，1.46 - 104.61；P = 0.021；以及风险比=5.2；95%置信区间，1.01 - 26.95；P = 0.048）。
年龄是APL的独立预后因素。在成年APL患者中，bcr-3与FLT3-ITD显著相关。DIC和FLT3-ITD是儿童APL患者的不良预后因素。尽管儿童风险较高，但其预后优于成人。
