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全反式维 A 酸和化疗治疗的急性早幼粒细胞白血病患者的附加染色体异常。

Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.

机构信息

Hospital Universitario La Fe, Avenida Campanar, 21, 46009 Valencia, Spain.

出版信息

Haematologica. 2010 Mar;95(3):424-31. doi: 10.3324/haematol.2009.013243. Epub 2009 Nov 10.

Abstract

BACKGROUND

Acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the t(15;17). The incidence and prognostic significance of additional chromosomal abnormalities in acute promyelocytic leukemia is still a controversial matter.

DESIGN AND METHODS

Based on cytogenetic data available for 495 patients with acute promyelocytic leukemia enrolled in two consecutive PETHEMA trials (LPA96 and LPA99), we analyzed the incidence, characteristics, and outcome of patients with acute promyelocytic leukemia with and without additional chromosomal abnormalities who had been treated with all-trans retinoic acid plus anthracycline monochemotherapy for induction and consolidation.

RESULTS

Additional chromosomal abnormalities were observed in 140 patients (28%). Trisomy 8 was the most frequent abnormality (36%), followed by abn(7q) (5%). Patients with additional chromosomal abnormalities more frequently had coagulopathy (P=0.03), lower platelet counts (P=0.02), and higher relapse-risk scores (P=0.02) than their counterparts without additional abnormalities. No significant association with FLT3/ITD or other clinicopathological characteristics was demonstrated. Patients with and without additional chromosomal abnormalities had similar complete remission rates (90% and 91%, respectively). Univariate analysis showed that additional chromosomal abnormalities were associated with a lower relapse-free survival in the LPA99 trial (P=0.04), but not in the LPA96 trial. However, neither additional chromosomal abnormalities overall nor any specific abnormality was identified as an independent risk factor for relapse in multivariate analysis.

CONCLUSIONS

The lack of independent prognostic value of additional chromosomal abnormalities in acute promyelocytic leukemia does not support the use of alternative therapeutic strategies when such abnormalities are found.

摘要

背景

急性早幼粒细胞白血病是急性髓细胞白血病的一种亚型,其特征是存在 t(15;17)。急性早幼粒细胞白血病中额外染色体异常的发生率和预后意义仍然存在争议。

设计和方法

基于在两项连续的 PETHEMA 试验(LPA96 和 LPA99)中可获得的 495 例急性早幼粒细胞白血病患者的细胞遗传学数据,我们分析了接受全反式维甲酸加蒽环类单药化疗诱导和巩固治疗的伴有和不伴有额外染色体异常的急性早幼粒细胞白血病患者的发生率、特征和结局。

结果

140 例患者(28%)存在额外染色体异常。三体 8 是最常见的异常(36%),其次是 abn(7q)(5%)。与不伴有额外异常的患者相比,伴有额外染色体异常的患者更常出现凝血障碍(P=0.03)、血小板计数更低(P=0.02)和复发风险评分更高(P=0.02)。未发现与 FLT3/ITD 或其他临床病理特征有显著关联。伴有和不伴有额外染色体异常的患者完全缓解率相似(分别为 90%和 91%)。单因素分析显示,在 LPA99 试验中,额外染色体异常与无复发生存率较低相关(P=0.04),但在 LPA96 试验中则不然。然而,多因素分析并未确定额外染色体异常总体或任何特定异常是复发的独立危险因素。

结论

额外染色体异常在急性早幼粒细胞白血病中缺乏独立的预后价值,这并不支持在发现这些异常时采用替代治疗策略。

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