【摘要】 背景:有报告显示,70%的慢性髓细胞性白血病患者异基因造血干细胞移植后1-5个月的细胞遗传学和基因标志检测阴性,但个别病例移植后1-3个月内反复变化,移植3-12个月的阴性率可达89.5%。目的:监测异基因造血干细胞移植治疗慢性髓细胞性白血病后的细胞分子遗传学标志变化,探讨其预后意义。方法:纳入异基因造血干细胞移植治疗慢性髓细胞性白血病患者17例,移植后30 d及2,3,4,6,12,24,36,48,60,72个月,采用骨髓细胞短期培养法和直接法G显带分析患者染色体,双色荧光原位杂交检测bcr/abl融合基因,RQ-PCR检测骨髓原代细胞的bcr/abl基因。结果与结论:17例患者中,8例为男患/男供者异基因造血干细胞移植,7例为男患/女供者异基因造血干细胞移植(同胞姐妹),移植后多次复查染色体核型为46XX(女性核型),未见Y染色体及其他畸变染色体核型;1例为女患/女供者异基因造血干细胞移植(其姐妹);1例为女患/无亲缘男供异基因造血干细胞移植,移植后1个月时染色体核型46XY,但bcr/abl阳性,4个月后持续表达46XY,bcr/abl阴性,观察超过96个月,为持续缓解,说明疗效良好;其中1男患/男供(全相合同胞弟)异基因造血干细胞移植后,1-12个月Ph染色体bcr/abl基因持续阳性表达,施行供者淋巴细胞输注,48个月后染色体bcr/abl转阴性表达,为持续缓解。结果表明,慢性髓细胞性白血病患者实施异基因造血干细胞移植后,染色体核型、bcr/abl融合基因监测对后续治疗选择、预后判断有重要参考价值。更多还原

【Abstract】 BACKGROUND: It has been reported that 70% of patients with chronic myeloid leukemia(CML) are negative for cytogenetic and genetic markers within 1-5 months after allogeneic hematopoietic stem cell transplantation(allo-HSCT), but there are still some patients who have repeatedly varied outcomes in cytogenetic and genetic marker detection. Overall, the negative rate is up to 89.5% at 3-12 months after allo-HSCT. OBJECTIVE: To monitor the changes in cytogenetic and genetic marker expression and to explore the prognostic significance in CML patients undergoing allo-HSCT. METHODS: Seventeen CML patients who had undergone allo-HSCT were enrolled. Chromosome G banding pattern of the bone marrow from these patients were analyzed using short-term culture method and direct method at 30 days, 2, 3, 4, 6, 12, 24, 36, 48, 60, 72 months after allo-HSCT. Dual-color fluorescence in situ hybridization was used to detect bcr-abl fusion gene; bcr-abl expressions in primary bone marrow cells from CML patients were detected using RQ-PCR. Results and conclusion: There were 8/17 cases of male patient/male donor and 7/17 cases of male patient/female donor(compatriots). 46 XX karyotype(women) was detected by multiple reexaminations after transplantation, and there was no Y chromosome or other aberration of chromosome karyotype in their karyotype. Among the 17 cases, 1 case of female patient/female donor(compatriots) and 1 case of female patient/male donor(unrelated) manifested 46 XY chromosome karyotype and bcr-abl positive at 1 month after transplantation; after 4 months, these two cases still maintained 46 XY chromosome karyotype but bcr-abl negative; after 4-96 months, the karyotype continued to remain as 46 XY, and bcr-abl(-). Among the 17 cases, 1 case of male patient/male donor of full-matched compatriot(brother) manifested that Ph chromosomal bcr-abl gene continuously expressed within 1-12 months after allo-HSCT; then the cases was given donor lymphocyte infusion, and the bcr-abl expression returned to be negative at 48 months after transplantation. To conclude, chromosomal karyotype analysis and bcr-abl fusion gene monitoring provide important reference value for subsequent treatment options and prognosis judgment for CML patients with allo-HSCT.更多还原