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曼尼托巴省的急性髓系白血病。标准“7 + 3”诱导缓解治疗后进行大剂量阿糖胞苷缓解后巩固治疗对骨髓抑制、感染发病率及预后的影响。

Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome.

作者信息

Bow E J, Kilpatrick M G, Scott B A, Clinch J J, Cheang M S

机构信息

Department of Medicine, University of Manitoba, Winnipeg, Canada.

出版信息

Cancer. 1994 Jul 1;74(1):52-60. doi: 10.1002/1097-0142(19940701)74:1<52::aid-cncr2820740110>3.0.co;2-g.

Abstract

BACKGROUND

To the authors' knowledge, the natural history of myelosuppression and infectious complications associated with the use of standard cytarabine (ARA-C) plus daunorubicin ("7 + 3") remission-induction therapy for adult acute myeloid leukemia (AML) and high dose ARA-C (HDARA-C) consolidation has not been described completely.

METHODS

A retrospective study of untreated adult AML patients receiving standard 7 + 3 induction followed by "5 + 2" and HDARA-C consolidation was undertaken to describe the relationship of the myelosuppression profiles, blood product use, and infectious morbidity, and to correlate this finding with the outcome of antileukemic therapy. Multivariate techniques were used to evaluate variables of prognostic importance.

RESULTS

Fifty-nine percent of the patients achieved remission after a median of 35 days; almost half (48%) of these patients required more than one 7 + 3 induction course. For one, two, and three induction courses, the mean number of days the patients experienced severe neutropenia (< 0.5 x 10(9)/l) were 22.5 +/- 10.9, 39.3 +/- 14.3, and 47.4 +/- 9.7 days (P < 0.001), respectively, and the infection rates were 1.45, 2.45, and 3 infections per course (P < 0.0001), respectively. The pattern of blood product use was similar. HDARA-C consolidation was the most significant factor related to prolonged disease free survival, however the myelosuppression profiles and infection rates were surprisingly similar to those for the single 7 + 3 induction courses.

CONCLUSIONS

The 7 + 3 induction regimen used in this center provided only limited antileukemic activity, while requiring multiple induction courses in a high proportion of patients. The use of multiple induction courses had consequences of prolonged myelosuppression, increased blood product use, and incremental risks of infectious complications. HDARA-C consolidation for those who experienced complete remission appeared to improve disease free survival with myelosuppression comparable with that of patients who received primary induction therapy. The infection risk was acceptable, with only a marginal increase in bacteremic and fungal infections.

摘要

背景

据作者所知,关于使用标准阿糖胞苷(ARA - C)联合柔红霉素(“7 + 3”)缓解诱导疗法治疗成人急性髓系白血病(AML)以及大剂量阿糖胞苷(HDARA - C)巩固治疗相关的骨髓抑制和感染并发症的自然病程尚未得到完整描述。

方法

对接受标准“7 + 3”诱导治疗,随后进行“5 + 2”和HDARA - C巩固治疗的未治疗成人AML患者进行回顾性研究,以描述骨髓抑制情况、血液制品使用情况与感染发病率之间的关系,并将这一发现与抗白血病治疗结果相关联。采用多变量技术评估具有预后重要性的变量。

结果

59%的患者在中位35天后达到缓解;其中近一半(48%)的患者需要超过一个“7 + 3”诱导疗程。对于一个、两个和三个诱导疗程,患者经历严重中性粒细胞减少(< 0.5×10⁹/L)的平均天数分别为22.5±10.9、39.3±14.3和47.4±9.7天(P < 0.001),感染率分别为每个疗程1.45次、2.45次和3次感染(P < 0.0001)。血液制品的使用模式相似。HDARA - C巩固治疗是与延长无病生存期最相关的因素,然而骨髓抑制情况和感染率与单次“7 + 3”诱导疗程的情况惊人地相似。

结论

该中心使用的“7 + 3”诱导方案仅提供有限的抗白血病活性,同时在很大比例的患者中需要多个诱导疗程。使用多个诱导疗程会导致骨髓抑制延长、血液制品使用增加以及感染并发症风险增加。对于实现完全缓解的患者,HDARA - C巩固治疗似乎可改善无病生存期,其骨髓抑制情况与接受初始诱导治疗的患者相当。感染风险是可接受的,菌血症和真菌感染仅略有增加。

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