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细胞遗传学和间期荧光原位杂交定义的13号染色体缺失在多发性骨髓瘤中的预后影响:总治疗方案II的早期结果

Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II.

作者信息

Shaughnessy John, Tian Erming, Sawyer Jeffrey, McCoy Jason, Tricot Guido, Jacobson Joth, Anaissie Elias, Zangari Maurizio, Fassas Athanasios, Muwalla Firas, Morris Christopher, Barlogie Bart

机构信息

Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

出版信息

Br J Haematol. 2003 Jan;120(1):44-52. doi: 10.1046/j.1365-2141.2003.03948.x.

Abstract

Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.

摘要

13号染色体的细胞遗传学异常(CA 13)以及通过荧光原位杂交检测到的异常(FISH 13)均与多发性骨髓瘤(MM)患者的不良预后相关。在参与全程治疗II的首批231例患者中,研究了CA、FISH 13及其他标准实验室参数的预后意义,全程治疗II是一项采用串联自体移植的强化细胞毒性化疗方案。无事件生存期(EFS)和总生存期(OS)的三年预测值分别为71%和77%。14%的患者检测到CA 13,且与FISH 13(51%的患者存在该异常)、肿瘤负荷、增殖活性和乳酸脱氢酶(LDH)显著相关。CA 13、FISH 13、LDH≥190 U/l、β2微球蛋白≥4 mg/l以及C反应蛋白≥4.0 mg/l的患者,其EFS和OS均显著缩短;其他细胞遗传学异常是OS的额外危险因素。三分之二的CA 13患者可通过FISH 13和浆细胞标记指数(PCLI)≥0.4%来识别;然而,PCLI未能在FISH亚组中识别出其他风险组。尽管CA 13患者数量少得多,但与FISH 13相比,CA 13导致更快的复发(3年时为61%)和死亡(3年时为43%,而FISH 13分别为38%和35%;P分别为0.02和0.1),应作为MM患者初始检查的一部分。

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