6-硫鸟嘌呤、阿糖胞苷和柔红霉素（TAD）以及高剂量阿糖胞苷和米托蒽醌（HAM）用于诱导治疗，TAD用于巩固治疗，对于各年龄段初发急性髓系白血病（AML）的成年患者，采用每月减量的TAD进行长期维持治疗或TAD-HAM-TAD方案，以及通过序贯HAM进行一个疗程的强化巩固治疗：德国AML协作组的一项随机试验

6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.

作者信息

Büchner Thomas, Hiddemann Wolfgang, Berdel Wolfgang E, Wörmann Bernhard, Schoch Claudia, Fonatsch Christa, Löffler Helmut, Haferlach Torsten, Ludwig Wolf-Dieter, Maschmeyer Georg, Staib Peter, Aul Carlo, Gruneisen Andreas, Lengfelder Eva, Frickhofen Norbert, Kern Wolfgang, Serve Hubert L, Mesters Rolf M, Sauerland Maria Cristina, Heinecke Achim

机构信息

University Medical Center, Department of Medicine, Hematology and Oncology, University of Muenster, Ulbert-Schweitzer-Str 33, D-48129 Muenster, Germany.

出版信息

J Clin Oncol. 2003 Dec 15;21(24):4496-504. doi: 10.1200/JCO.2003.02.133.

DOI:10.1200/JCO.2003.02.133

PMID:14673036

Abstract

PURPOSE

To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML).

MATERIALS AND METHODS

Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age > or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age > or = 60 years) x 8 instead of maintenance.

RESULTS

A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026).

CONCLUSION

We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

摘要

目的

探讨延长维持化疗与强化巩固化疗对急性髓系白血病（AML）患者的疗效。

材料与方法

832例初发AML患者（中位年龄54岁；范围16至82岁）被随机分配接受6-硫鸟嘌呤、阿糖胞苷和柔红霉素（TAD）加阿糖胞苷和米托蒽醌（HAM；阿糖胞苷3 g/m²[年龄<60岁]或1 g/m²[年龄≥60岁]×6）诱导治疗、TAD巩固治疗以及为期3年的每月改良TAD维持治疗，或TAD-HAM-TAD方案及一个疗程的强化巩固治疗，即序贯使用阿糖胞苷1 g/m²（年龄<60岁）或0.5 g/m²（年龄≥60岁）×8的HAM（S-HAM），而非维持治疗。

结果

共有69.2%的患者达到完全缓解（CR）。维持治疗组患者的中位无复发生存期（RFS）为19个月，5年无复发患者比例为31.4%；而S-HAM组患者的中位RFS为12个月，5年无复发患者比例为24.7%（P = 0.0118）。对于具有不良核型、年龄≥60岁、乳酸脱氢酶水平大于700 U/L或第16天骨髓原始细胞大于40%等不良风险因素的患者，维持治疗的RFS更优（P = 0.0061），但对于完全不存在任何不良风险因素的低风险患者则不然。尽管CR患者的生存获益不显著（P = 0.085），但维持治疗组仍处于首次CR的存活患者多于S-HAM组（P = 0.026）。