间期细胞遗传学对多发性骨髓瘤患者生存的预测作用

Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.

作者信息

Königsberg R, Zojer N, Ackermann J, Krömer E, Kittler H, Fritz E, Kaufmann H, Nösslinger T, Riedl L, Gisslinger H, Jäger U, Simonitsch I, Heinz R, Ludwig H, Huber H, Drach J

机构信息

First Department of Internal Medicine, Divisions of Clinical Oncology, University of Vienna, Vienna, Austria.

出版信息

J Clin Oncol. 2000 Feb;18(4):804-12. doi: 10.1200/JCO.2000.18.4.804.

DOI:10.1200/JCO.2000.18.4.804

PMID:10673522

Abstract

PURPOSE

Recent metaphase cytogenetic studies suggested that specific chromosomal abnormalities are of prognostic significance in patients with multiple myeloma (MM). Because the true incidence of chromosomal abnormalities in MM is much higher than that detected by metaphase analysis, we used interphase fluorescence in situ hybridization (FISH) to determine the prognostic value of specific chromosomal aberrations.

PATIENTS AND METHODS

Bone marrow plasma cells from 89 previously untreated patients with MM were studied consecutively by FISH to detect the deletions of 13q14, 17p13, and 11q and the presence of t(11;14)(q13;q32). FISH results were analyzed in the context of clinical parameters (response to treatment and survival after conventional-dose chemotherapy), and a multivariate analysis of prognostic factors was performed.

RESULTS

By FISH, the deletion of 13q14 occurred in 40 patients (44.9%), deletion of 17p13 in 22 (24.7%), and 11q abnormalities in 14 (15.7%; seven with t(11;14)). Deletions of 13q14 and 17p13 were associated with poor response to induction treatment (46.9% v 77.3% in those without deletions, P =.006 and 40.0% v 73.2%, P =.008, respectively) and short median overall survival (OS) time (24.2 v 88.1 months, P =. 008 and 16.2 v 51.3 months, P =.008, respectively). Short median OS time was also observed for patients with 11q abnormalities (13.1 v 41.6 months, P =.02). According to the number of unfavorable cytogenetic features (deletion of 13q14, deletion of 17p13, and aberrations of 11q) that were present in each patient (0 v 1 v 2 or 3), patients with significantly different OS times could be discriminated from one another (102.4 v 29.6 v 13.9 months, P <.001, respectively).

CONCLUSION

For patients with MM who were treated with conventional-dose chemotherapy, interphase FISH for 13q14, 17p13, and 11q provides prognostically relevant information in addition to that provided by standard prognostic factors. This observation may be considered for risk-adapted stratifications of MM patients in future clinical trials.

摘要

目的

近期的中期细胞遗传学研究表明，特定的染色体异常对多发性骨髓瘤（MM）患者具有预后意义。由于MM中染色体异常的实际发生率远高于中期分析所检测到的，我们采用间期荧光原位杂交（FISH）来确定特定染色体畸变的预后价值。

患者与方法

对89例既往未经治疗的MM患者的骨髓浆细胞进行连续FISH检测，以检测13q14、17p13和11q的缺失以及t(11;14)(q13;q32)的存在情况。结合临床参数（对治疗的反应和常规剂量化疗后的生存情况）对FISH结果进行分析，并对预后因素进行多变量分析。

结果

通过FISH检测，40例患者（44.9%）存在13q14缺失，22例（24.7%）存在17p13缺失，14例（15.7%；7例伴有t(11;14)）存在11q异常。13q14和17p13缺失与诱导治疗反应不佳相关（无缺失者分别为46.9%对77.3%，P = 0.006；40.0%对73.2%，P = 0.008），且总生存（OS）期中位数较短（分别为24.2对88.1个月，P = 0.008；16.2对51.3个月，P = 0.008）。11q异常的患者OS期中位数也较短（13.1对41.6个月，P = 0.02）。根据每位患者存在的不良细胞遗传学特征（13q14缺失、17p13缺失和11q畸变）数量（0对1对2或3），可区分出OS期明显不同的患者（分别为102.4对29.6对13.9个月，P < 0.001）。