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通过bcr-abl mRNA和DNA指纹图谱预测异基因骨髓移植后慢性粒细胞白血病的复发

Predicting relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation by bcr-abl mRNA and DNA fingerprinting.

作者信息

Okamoto R, Harano H, Matsuzaki M, Motomura S, Maruta A, Kodama F, Mohri H, Okubo T

机构信息

First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.

出版信息

Am J Clin Pathol. 1995 Nov;104(5):510-6. doi: 10.1093/ajcp/104.5.510.

DOI:10.1093/ajcp/104.5.510
PMID:7572810
Abstract

Fourteen patients treated by allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr-abl-specific transcripts. Nine patients were transplanted in the first chronic phase, three in the second chronic phase, and two in the accelerated phase. All patients achieved a complete cytogenetic and hematologic remission after bone marrow transplantation. Twelve patients are alive (median, 18 months; range, 5-54 months) and two patients died early. bcr-abl mRNA was persistently detectable for 6 to 54 months in four patients (patients 1, 3, 4, 6). From two of them, DNA fingerprint analysis showed only donor type DNA although bcr-abl mRNA was detectable. bcr-abl mRNA was never detectable posttransplant in three patients (patients 2, 5, 13). Six patients had detectable bcr-abl mRNA (patients 8-12, 14): by 6 months, all of these patients were bcr-abl mRNA negative. One patient (patient 7) had detectable full bcr-abl mRNA again at 12 months, but was then negative at 20 months. Ten patients (patients 2, 4-8, 10-13) had never detectable Philadelphia (Ph1) chromosome t(9.22) translocation, whereas four patients had detectable Ph1 (patient 1, 3, 9, 14); by 6 months, three of four cases were negative. One patient (patient 1) had detectable Ph1 at 44 months, but was negative at 50 months. Three of six patients who initially had bcr-abl mRNA detectable posttransplant (patient 7-9) became negative for bcr-abl mRNA at the time of development of chronic graft-versus-host disease (GVHD). These results suggest that the detection of subclinical Ph1 positive cells by PCR is not associated with imminent clinical or cytogenetic relapse. Moreover, graft-versus-leukemia (GVL) activity may contribute to the treatment of minimal residual disease in CML after allogeneic bone marrow transplantation.

摘要

对14例接受异基因骨髓移植治疗慢性粒细胞白血病(CML)的患者进行了聚合酶链反应(PCR)检测,以分析bcr-abl特异性转录本。9例患者处于慢性期I接受移植,3例处于慢性期II,2例处于加速期。所有患者骨髓移植后均实现了完全细胞遗传学和血液学缓解。12例患者存活(中位时间18个月;范围5 - 54个月),2例患者早期死亡。4例患者(患者1、3、4、6)在6至54个月期间持续检测到bcr-abl mRNA。其中2例患者,尽管可检测到bcr-abl mRNA,但DNA指纹分析仅显示供体类型的DNA。3例患者(患者2、5、13)移植后从未检测到bcr-abl mRNA。6例患者(患者8 - 12、14)可检测到bcr-abl mRNA:到6个月时,所有这些患者的bcr-abl mRNA均呈阴性。1例患者(患者7)在12个月时再次检测到完整的bcr-abl mRNA,但在20个月时呈阴性。10例患者(患者2、4 - 8、10 - 13)从未检测到费城(Ph1)染色体t(9;22)易位,而4例患者可检测到Ph1(患者1、3、9、14);到6个月时,4例中的3例呈阴性。1例患者(患者1)在44个月时可检测到Ph1,但在50个月时呈阴性。6例最初移植后可检测到bcr-abl mRNA的患者中有3例(患者7 - 9)在慢性移植物抗宿主病(GVHD)发生时bcr-abl mRNA变为阴性。这些结果表明,通过PCR检测亚临床Ph1阳性细胞与即将发生的临床或细胞遗传学复发无关。此外,移植物抗白血病(GVL)活性可能有助于异基因骨髓移植后CML微小残留病的治疗。

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