Ravindranath Y, Abella E, Krischer J P, Wiley J, Inoue S, Harris M, Chauvenet A, Alvarado C S, Dubowy R, Ritchey A K
Children's Hospital of Michigan, Wayne State University, Detroit.
Blood. 1992 Nov 1;80(9):2210-4.
The treatment of acute myeloid leukemia (AML) in children with Down's syndrome (DS) has engendered considerable controversy. Because of the concerns for toxicity and increased rate of infections, treatment approaches varied considerably in the past with mixed results. However, experience on the recently completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children with AML constitute a distinct subgroup that responds well to therapy. Twelve of 285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An abnormal cytogenetic marker, in addition to constitutional trisomy 21, was present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5) were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and, interestingly, were also positive for the CD7 antigen. Chemotherapy included daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early in remission. Compared with children without DS, children with DS had a superior event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS remained superior even when compared with non-DS children less than 2 years of age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/- 17.3%; P = .01).
唐氏综合征（DS）患儿急性髓系白血病（AML）的治疗引发了诸多争议。由于担心毒性和感染率增加，过去治疗方法差异很大，结果不一。然而，最近完成的儿童肿瘤学组（POG）8498 AML研究的经验表明，患有AML的DS患儿构成了一个对治疗反应良好的独特亚组。POG 8498（新诊断AML方案）的285名儿童中有12名患有DS。患有DS和AML的儿童以男性为主（12名中有9名），诊断时年龄较小（10名小于24个月）。所有12名患儿的白细胞计数均低于50×10³/μL，且常见法美英分型中的M6和M7型（12名中有5名）。12名患儿中有9名除了21号染色体三体异常外，还存在异常细胞遗传学标记，其中9名中有4名涉及8号染色体。所有研究病例（n = 5）髓系细胞表面标志物（CD33、CD13或CD11b）均为阳性，有趣的是，CD7抗原也呈阳性。化疗包括柔红霉素、阿糖胞苷（Ara-C）和6-硫鸟嘌呤用于诱导缓解，缓解早期采用高剂量Ara-C（每剂量3 g/m²），联合或不联合左旋门冬酰胺酶。与无DS的儿童相比，患有DS的儿童无事件生存率更高（4年无事件生存率为100%对28%±6.2%；P = 0.003）。即使与年龄小于2岁、白细胞计数低于10×10⁵/μL的非DS儿童相比，无事件生存率仍更高（100%对48%±17.3%；P = 0.01）。
