儿童急性淋巴细胞白血病的强化化疗：随机国际临床试验 ALL IC-BFM 2002 的结果。

Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002.

机构信息

Jan Stary, Jan Trka, and Ondrej Hrusak, Charles University and University Hospital Motol, Prague; Yahia Jabali, Regional Hospital, Ceske Budejovice, Czech Republic; Martin Zimmermann and Hansjörg Riehm, Medical School Hannover, Hannover; Martin Schrappe, University Hospital Schleswig-Holstein, Kiel, Germany; Myriam Campbell, Roberto del Rio Hospital, Universidad de Chile, Santiago, Chile; Luis Castillo, Hospital Pereira Rossell, Montevideo, Uruguay; Eduardo Dibar, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Svetlana Donska, Regional Oncologic Hospital, Kiev, Ukraine; Alejandro Gonzalez, Institute of Hematology and Immunology, La Habana, Cuba; Shai Izraeli, Sheba Medical Center of Israel, Sackler School of Medicine, Tel Aviv University, Tel Hashomer; Batia Stark, Schneider Children's Medical Center of Israel, Sackler School of Medicine, Tel Aviv University, Petah-Tikva, Israel; Dragana Janic, University Children's Hospital, University of Belgrade, Belgrade, Serbia; Janez Jazbec, University Children's Hospital, Ljubljana, Slovenia; Josip Konja, University Hospital Centre Rebro, Zagreb, Croatia; Emilia Kaiserova, University Children's Hospital, Bratislava, Slovakia; Jerzy Kowalczyk, University of Lublin, Lublin, Poland; Gabor Kovacs and Edina Magyarosy, Semmelweis University, Budapest, Hungary; Chi-Kong Li, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People's Republic of China; Alexander Popa, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia; and Giuseppe Masera, Ospedale S. Gerardo, University of Milano-Bicocca, Monza, Italy.

出版信息

J Clin Oncol. 2014 Jan 20;32(3):174-84. doi: 10.1200/JCO.2013.48.6522. Epub 2013 Dec 16.

DOI:10.1200/JCO.2013.48.6522

PMID:24344215

Abstract

PURPOSE

From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups.

PATIENTS AND METHODS

For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option).

RESULTS

At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI.

CONCLUSION

The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.

摘要

目的

从 2002 年到 2007 年，国际柏林-法兰克福-明斯特研究组在三大洲的 15 个国家进行了一项儿童急性淋巴细胞白血病（ALL）的前瞻性随机临床试验（ALL IC-BFM 2002）。该试验的目的是探讨不同的延迟强化（DI）对所有风险组的结果的影响。

方法

对于这项试验，5060 名合格的患者根据年龄、白细胞计数、早期治疗反应和不良遗传异常被分为三个风险组。DI 被随机分为以下三组：标准风险（SR），两个 4 周强化元素（方案 III）与一个 7 周方案 II；中间风险（IR），方案 III × 3 与方案 II × 1；高风险（HR），方案 III × 3 与方案 II × 2（意大利儿科血液学和肿瘤学协会[AIEOP]选项），或 3 个 HR 块加一个单独的方案 II（柏林-法兰克福-明斯特[BFM]选项）。