田蕙芬2006-07-262018-07-112006-07-262018-07-112003http://ntur.lib.ntu.edu.tw//handle/246246/23584From June 1987 to October 2003, bone marrow (BM) cells obtained from 160 patients with previously untreated multiple myeloma (MM) were analyzed by conventional cytogenetic (CC) method and 57 of the BM samples were also analyzed by interphase DNA fluorescence in situ hybridization (FISH) using multiple probes specific for chromosome 13q14, 17p13, centromeric 3, 7, 11, and 18. We aimed at (1) studying the frequency of cytogenetic aberrations in our MM patients, (2) investigating the independent significance of CC and FISH results in clinical ground, in terms of response to conventional chemotherapy, duration of response and overall survival (OS). Among those 160 patients, 109 (68.1%) were men, 51 (31.9%) were women, the median age at diagnosis was 62 years (range, 24 to 88). Fifteen (10.0%) of them were Durie-Salmon stage I, 32 (21.3%) were stage II, 50 (33.3%) were stage IIIa and 53 (35.3%) were stage IIIb. By CC analysis, cytogenetic aberrations were detected in 40 patients (25.6%). Patients with stage IIIb had higher incidence of cytogenetic aberrations than those with stage I disease, 29.4% vs. 13.3%, respectively. Among the 39 patients, complex cytogenetic aberrations occurred in 29 patients (74.4%), and 14 patients (50%) had hyperdiploidy, 6 patients (21.4%) had hypodiploidy, 2 patients (7.2%) had triploidy. The most common numeric change was trisomy 9, followed by trisomy 15 and monosomy 13. The most common structural change was 1q duplication, followed by 14q32 abnormalities, including three with t(11;14)(q13;q32) and one with t(6;14)(p21;q32). Intriguingly, add (19)(p13) was a non-random chromosome aberration, which occurred in 3 patients who all had extramedullary plasmacytomas at diagnosis. In this study, there was no significant difference in the treatment response rate (65% vs. 62.5%, p=0.846), duration of response (median, 8±4.6 vs. 12±2 months, p=0.276) or OS (median, 11±3.2 vs. 28±6.4 months, p=0.067) between those patients with cytogenetic aberrations and those without. On univariate analysis, chromosome 1q duplication was significantly associated with short OS (median, 9±2.6 vs. 27±5 months, p=0.022), so as partial or complete loss of chromosome 13 and/or abnormalities involving chromosome 11q (12±2.5 months vs. 28±7.1, p=0.028). However, on Cox stepwise regression analysis including conventional prognostic factors and the cytogenetic aberrations, only stage (p=0.003) was a independent prognostic factor for OS. In the 57 BM samples analyzed by FISH, at least one of the non-random chromosome aberrations were detected in 33 samples (57.9%), including 13q deletion in 30% of samples, 17p deletion in 5.5%, trisomy 3 in 22.2%, trisomy 7 in 24.1%, trisomy 11 in 22.2%, and trisomy 18 in 13%. Of note, FISH had higher sensitivity than CC in detecting chromosome aberrations in MM; for example, 13q & 17p deletions were found only in 11.3% and 1.9% of the patients respectively, by CC. Although 13q deletion was associated with poor response to conventional chemotherapy (46.7% vs. 72.4%, p=0.092) and short median OS (24±13 vs. 28±10.5 months, p=0.16), these differences were below the level of statistical significance, which was probably resulted from limited number of samples. In this study, trisomy 18 was associated with short duration of response (3 months vs. 14±4 months, p=0.03). In summary, 25% of our MM patients have cytogenetic aberrations by CC method. FISH revealed higher sensitivity than CC in detecting the non-random aberrations. Chromosome 1q, partial or complete loss of chromosome 13q and/or chromosome 11q abnormalities might be associated with poor clinical outcome in MM, but need to be confirmed by further studies on more patients.application/pdf103609 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23584/1/912314B002131.pdf