Winick N J, McKenna R W, Shuster J J, Schneider N R, Borowitz M J, Bowman W P, Jacaruso D, Kamen B A, Buchanan G R
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
J Clin Oncol. 1993 Feb;11(2):209-17. doi: 10.1200/JCO.1993.11.2.209.
To describe the occurrence of secondary acute myeloid leukemia (AML) in children with acute lymphoblastic leukemia (ALL) treated with etoposide (VP-16).
Two hundred five consecutive children with early B-lineage ALL were treated according to the Dallas/Fort Worth (DFW) protocol between January 1986 and July 1, 1991. Therapy included a four-drug induction followed by consolidation and continuation phases of nightly oral mercaptopurine (6-MP) and repetitive courses of divided-dose oral methotrexate (dMTX) and asparaginase (L-asp). Three doses of VP-16 and cytarabine (Ara-C) were given during consolidation and later, during continuation, two doses were given 3 to 4 days apart, every 9 weeks. Intrathecal (IT) chemotherapy was given throughout the treatment period.
Two hundred three of the 205 patients entered remission. Only eight of these 203 children have had a bone marrow relapse (ALL). However, 10 other children have developed secondary AML 23 to 68 months following the diagnosis of ALL. Overall event-free survival (EFS) at 4 years is 79.3% +/- 5.1%, with a risk of secondary AML at 4 years of 5.9% +/- 3.2%.
This experience provides strong evidence for a link between epipodophyllotoxin therapy and secondary AML since none of these children received alkylating agent therapy or irradiation. This serious complication raises concern as to the appropriate use of epipodophyllotoxins in the treatment of childhood ALL.
描述接受依托泊苷（VP - 16）治疗的急性淋巴细胞白血病（ALL）患儿发生继发性急性髓系白血病（AML）的情况。
1986年1月至1991年7月1日期间，205例连续的早期B系ALL患儿按照达拉斯/沃思堡（DFW）方案进行治疗。治疗包括四药诱导，随后是巩固期和延续期，巩固期为每晚口服巯嘌呤（6 - MP），延续期为分剂量口服甲氨蝶呤（dMTX）和天冬酰胺酶（L - asp）的重复疗程。在巩固期给予3剂VP - 16和阿糖胞苷（Ara - C），之后在延续期，每9周间隔3至4天给予2剂。整个治疗期间均给予鞘内（IT）化疗。
205例患者中有203例进入缓解期。这203例患儿中只有8例发生骨髓复发（ALL）。然而，另有10例患儿在ALL诊断后23至68个月发生了继发性AML。4年时的总体无事件生存率（EFS）为79.3%±5.1%，4年时继发性AML的风险为5.9%±3.2%。
由于这些患儿均未接受烷化剂治疗或放疗，该经验为表鬼臼毒素治疗与继发性AML之间的关联提供了有力证据。这种严重并发症引发了对表鬼臼毒素在儿童ALL治疗中合理使用的关注。
