Ravindranath Y, Steuber C P, Krischer J, Civin C I, Ducore J, Vega R, Pitel P, Inoue S, Bleher E, Sexauer C
Wayne State University School of Medicine, Detroit, MI.
J Clin Oncol. 1991 Apr;9(4):572-80. doi: 10.1200/JCO.1991.9.4.572.
In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4) followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%] v 34% [SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/microL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children greater than or equal to 2 years and those with WBCs greater than or equal to 100,000/microL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.
1984年6月，儿科肿瘤研究组（POG）启动了一项试点研究（8498），使用大剂量阿糖胞苷（HdA；3 g/m²）强化儿童急性髓性白血病（AML）的早期治疗（第一组）。缓解诱导治疗包括两个疗程的柔红霉素、阿糖胞苷（Ara-C）和硫鸟嘌呤（DAT）。缓解后治疗包括四个连续疗程，每个疗程包括：（1）四剂HdA（HdA4），随后是天冬酰胺酶（L-Asp）；（2）依托泊苷（VP）加阿扎胞苷（Az）；（3）泼尼松、长春新碱、甲氨蝶呤和巯嘌呤（POMP）；（4）连续输注阿糖胞苷每日5天。给予六剂鞘内注射阿糖胞苷进行中枢神经系统预防。1986年12月，方案进行了修订（第二组），用六剂HdA（HdA6）替代第二个DAT（两剂加五剂）诱导疗程；诱导后，给予一个疗程的HdA6，而不是四个HdA/L-Asp疗程，其余治疗不变。140例第一组患者和145例第二组患者可进行评估。两组在临床预后分组方面相似。两组在缓解诱导（每组85%[标准误=2%]）、诱导期死亡（6.5%对7.0%）或缓解期死亡（每组各1例）方面无显著差异。第二组（使用HdA6）有3例患者报告有小脑毒性，而第一组（HdA4）无。目前，接受HdA6治疗的患者（第二组）的无事件生存率高于第一组患者（3年无事件生存率，34%[标准误=11%]对29%[标准误=4%]），无病生存率（3年无病生存率，42%[标准误=14%]对34%[标准误=4%]），但差异无统计学意义。在两组中，年龄小于2岁且白细胞计数低于100,000/μL的儿童的预后（3年无事件生存率分别为55%[标准误=10%]和36%[标准误=5%]）明显好于年龄大于或等于2岁且白细胞计数大于或等于100,000/μL的儿童（3年无事件生存率分别为27%[标准误=5%]和20%[标准误=9%]）。
