根据费城染色体/BCR-ABL重排在B前体成人急性淋巴细胞白血病中的表达情况，早期蒽环类药物剂量强度的作用

Role of early anthracycline dose-intensity according to expression of Philadelphia chromosome/BCR-ABL rearrangements in B-precursor adult acute lymphoblastic leukemia.

作者信息

Bassan R, Rohatiner A Z, Lerede T, Di Bona E, Rambaldi A, Pogliani E, Rossi G, Fabris P, Morandi S, Casula P, Carter M, Lambertenghi-Deliliers G, Lister T A, Barbui T

机构信息

Divisione di Ematologia, Ospedali Riuniti, Largo Barozzi 1, 24100 Bergamo, Italy.

出版信息

Hematol J. 2000;1(4):226-34. doi: 10.1038/sj.thj.6200032.

DOI:10.1038/sj.thj.6200032

PMID:11920195

Abstract

INTRODUCTION

The use of anthracycline antibiotics in adult acute lymphoblastic leukemia (ALL) has resulted in an improved outcome to remission induction therapy. However,the exact role of these drugs in consolidation therapy is less clear, especially in specific ALL subsets.

MATERIALS AND METHODS

A retrospective analysis was conducted on the outcome of 308 patients (median age 35 years, range 13-75) with the most frequent subtype, early-B ALL, treated between 1974 and 1998 on eight consecutive protocols. Anthracycline-related effects were assessed by evaluating the impact of planned anthracycline dose-intensity (A-DI) on long-term outcome. A-DI (in mg/m(2)/week) during the first twelve weeks of consolidation therapy was classified as either "high" (doxorubicin>20, idarubicin>7) or "low".

RESULTS

Complete remission was achieved in 78% of cases. With a median follow-up of 6.5 years, on multivariate analysis, disease-free survival (DFS) correlated only with expression of the Philadelphia (Ph) chromosome and/or associated BCR-ABL rearrangements (Ph/BCR(+)) (P=0.0001) and planned A-DI (P<0.0001). On this basis, four major prognostic groups with significantly different DFS could be identified: (1) Ph/BCR(-), "high" A-DI (n=102), median 3.5 years and 41% at five years, respectively; (2) Ph/BCR(-), "low" A-DI (n=64), 1.3 years and 16%; (3) Ph/BCR(+), "high" A-DI (n=35), 1.7 years and 20%; (4) Ph/BCR(+), "low" A-DI (n=39), 0.75 years and 0%. When analyzed separately for Ph/BCR(-) (n=166) and Ph/BCR(+) (n=74) patients, the A-DI effect on DFS was preserved in the former (P=0.018) whereas, in Ph/BCR(+) patients, only age <50 years (P=0.004) and blast count <25 x 10(9)/l (P=0.02) correlated with better DFS. However, Ph/BCR(+) patients with the best prognostic profile (age <50 years and blast count <25 x 10(9)/l; n=21) who were treated on "high" A-DI regimens experienced a median DFS of 2.2 years with DFS 21% at five years, compared to 0.67-1 years and 0-10% in other cases (n=53, P<0.01).

CONCLUSION

A "high" A-DI may act as a positive treatment-related prognostic factor in early B-lineage ALL. Although mainly restricted to patients with Ph/BCR(-) ALL, A-DI could also influence the outcome in Ph/BCR(+) patients with other favorable prognostic factors.

摘要

引言

在成人急性淋巴细胞白血病（ALL）中使用蒽环类抗生素已使缓解诱导治疗的结果得到改善。然而，这些药物在巩固治疗中的确切作用尚不清楚，尤其是在特定的ALL亚组中。

材料与方法

对1974年至1998年间按照八个连续方案治疗的308例最常见亚型即早期B-ALL患者（中位年龄35岁，范围13 - 75岁）的治疗结果进行回顾性分析。通过评估计划的蒽环类药物剂量强度（A-DI）对长期结果的影响来评估蒽环类药物相关效应。巩固治疗前十二周的A-DI（以mg/m²/周计）分为“高”（多柔比星>20，伊达比星>7）或“低”。

结果

78%的病例实现完全缓解。中位随访6.5年，多因素分析显示，无病生存期（DFS）仅与费城（Ph）染色体表达和/或相关的BCR-ABL重排（Ph/BCR(+)）（P = 0.0001）以及计划的A-DI（P < 0.0001）相关。在此基础上，可以确定四个DFS有显著差异的主要预后组：（1）Ph/BCR(-)，“高”A-DI（n = 102），五年时的中位DFS分别为3.5年和41%；（2）Ph/BCR(-)，“低”A-DI（n = 64），1.3年和16%；（3）Ph/BCR(+)，“高”A-DI（n = 35），1.7年和20%；（4）Ph/BCR(+)，“低”A-DI（n = 39），0.75年和0%。对Ph/BCR(-)（n = 166）和Ph/BCR(+)（n = 74）患者分别进行分析时，A-DI对DFS的影响在前者中仍然存在（P = 0.018），而在Ph/BCR(+)患者中，只有年龄<50岁（P = 0.004）和原始细胞计数<25×10⁹/l（P = 0.02）与更好的DFS相关。然而，接受“高”A-DI方案治疗的预后最佳的Ph/BCR(+)患者（年龄<50岁且原始细胞计数<25×10⁹/l；n = 21）的中位DFS为2.2年，五年时DFS为21%，相比之下其他病例（n = 53）为0.67 - 1年和0 - 10%（P < 0.01）。