Kern Wolfgang, Haferlach Torsten, Schoch Claudia, Loffler Helmut, Gassmann Winfried, Heinecke Achim, Sauerland Maria Christina, Berdel Wolfgang, Buchner Thomas, Hiddemann Wolfgang
Ludwig-Maximilians-University, University Hospital Grosshadern, Department of Internal Medicine III, Muenchen, Germany.
Blood. 2003 Jan 1;101(1):64-70. doi: 10.1182/blood-2002-02-0532. Epub 2002 Jun 28.
Risk assessment in acute myeloid leukemia (AML) using pretreatment characteristics may be improved by incorporating parameters of early response to therapy. In the 1992 trial of the German AML Cooperative Group (AMLCG), the amount of residual leukemic blasts in bone marrow was assessed one week after the first induction course (day 16 blasts). A total of 449 patients 16 to 76 years of age (median, 53 years) with de novo AML entered the trial and were evaluable. Treatment included TAD/HAM (thioguanine, cytosine arabinoside, and daunorubicin/high-dose cytosine arabinoside and mitoxantrone) double induction, TAD consolidation, and randomly either maintenance therapy or S-HAM consolidation. Cytogenetics were favorable, intermediate, unfavorable and not available in 10.0%, 48.3%, 13.1%, and 28.5%, respectively. Day 16 blasts ranged from 0% to 100% (median, 5%, mean +/- SD, 18.6 +/- 28.5%). Complete remission (CR) rate was 72.6%, 17.6% had persistent leukemia (PL), and 9.8% succumbed to hypoplastic death. Median overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were 18, 9, and 15 months with 28.4%, 21.6%, and 30.1% at 5 years, respectively. As a continuous variable, day 16 blasts were related to CR rate (P < 0.0001), PL rate (P < 0.0001), OS (P < 0.0001), EFS (P < 0.0001), and RFS (P = 0.0049). Multivariate analyses identified the following parameters to be associated with the respective end points. CR rate: day 16 blasts (P <.0001), age (P =.0036), and LDH (P =.0072); OS: unfavorable cytogenetics (P <.0001), day 16 blasts (P <.0001), age (P <.0001), and LDH (P =.0040); EFS: unfavorable cytogenetics (P <.0001), LDH (P <.0001), day 16 blasts (P <.0001), and age (P =.0061); RFS: unfavorable cytogenetics (P <.0001), LDH (P <.0001), and day 16 blasts (P =.0359). The prognostic significance of day 16 blasts is independent of pretherapeutic parameters and predicts outcome even in patients achieving a CR.
通过纳入治疗早期反应参数，利用预处理特征进行急性髓系白血病（AML）的风险评估可能会得到改善。在1992年德国AML协作组（AMLCG）的试验中，在第一个诱导疗程后一周（第16天的原始细胞）评估骨髓中残留白血病原始细胞的数量。共有449例16至76岁（中位数53岁）的初发AML患者进入试验并可进行评估。治疗包括TAD/HAM（硫鸟嘌呤、阿糖胞苷和柔红霉素/大剂量阿糖胞苷和米托蒽醌）双诱导、TAD巩固，以及随机分组进行维持治疗或S-HAM巩固。细胞遗传学结果为良好、中等、不良和不可评估的分别占10.0%、48.3%、13.1%和28.5%。第16天的原始细胞比例范围为0%至100%（中位数5%，均值±标准差，18.6±28.5%）。完全缓解（CR）率为72.6%，17.6%有持续性白血病（PL），9.8%死于造血功能低下。中位总生存期（OS）、无事件生存期（EFS）和无复发生存期（RFS）分别为18个月、9个月和15个月，5年时分别为28.4%、21.6%和30.1%。作为连续变量，第16天的原始细胞与CR率（P<0.0001）、PL率（P<0.0001）、OS（P<0.0001）、EFS（P<0.0001）和RFS（P = 0.0049）相关。多变量分析确定以下参数与各自的终点相关。CR率：第16天的原始细胞（P<.0001）、年龄（P =.0036）和乳酸脱氢酶（LDH）（P =.0072）；OS：不良细胞遗传学（P<0.千分之一）、第16天的原始细胞（P<0.千分之一）、年龄（P<0.千分之一）和LDH（P =.0040）；EFS：不良细胞遗传学（P<0.千分之一）、LDH（P<0.千分之一）、第16天的原始细胞（P<0.千分之一）和年龄（P =.0061）；RFS：不良细胞遗传学（P<0.千分之一）、LDH（P<0.千分之一）和第16天的原始细胞（P =.0359）。第16天原始细胞的预后意义独立于治疗前参数，即使在达到CR的患者中也能预测预后。
