摘要
背景:bcr-abl融合基因不仅是慢性粒细胞白血病的诊断标准,其水平的变化也是判断病情或疗效的惟一指标,尤其是bcr-abl融合基因的动态变化对于异基因造血干细胞移植效果的评估和预后判断可能更为重要。目的:了解慢性粒细胞白血病患者异基因造血干细胞移植后bcr-abl融合基因水平的变化情况。设计:回顾性病例分析。对象:2001-04/2007-01在广东省人民医院血液科收治的确诊1年内行异基因造血干细胞移植的慢性粒细胞白血病患者22例,中位年龄31.5岁,患者对治疗均签署知情同意书,治疗方案经医院医学伦理委员会批准。方法:所有同胞供者均采用粒细胞集落刺激因子行外周血干细胞动员。所有患者均采用改良BU/CY联合FLU预处理方案,供受者血型不相合者于移植前7d、1d行血浆置换以降低血型抗体滴度。患者经深静脉输入同胞供者平均单个核细胞数为5.48×108/kg,平均CD34+细胞数为10.45×106/kg。由于移植和随访时间不同,每例患者收集标本3～14份,共130份外周血标本。主要观察指标:通过实时荧光定量PCR法检测22例患者异基因造血干细胞移植后不同时间130份外周血标本中bcr-abl融合基因的水平。结果:移植后6个月内,bcr-abl融合基因总体水平逐渐降低,移植后1、3、6个月bcr-abl阴性患者的比例分别为33.33%、53.33%和84.62%,bcr-abl高水平阳性(bcr-abl/abl≥0.02%)患者的比例分别为58.33%、33.33%和15.38%,低水平阳性(bcr-abl/abl<0.02%)患者的比例分别为8.33%、13.33%和0。移植6个月后,多数患者连续多次检测不到bcr-abl融合基因,其中持续阴性者9例(69.23%),低水平波动者1例(7.69%),低水平持续阳性者1例(7.69%),复发2例(15.38%);复发的2例患者移植后6个月内连续检测bcr-abl融合基因水平均未降低至0,且3次检测结果中2次属于高水平阳性。结论:异基因造血干细胞移植后,慢性粒细胞白血病患者bcr-abl融合基因总体水平逐渐下降,但不同患者bcr-abl变化情况各异,通过实时定量PCR检测可明确其变化趋势。
BACKGROUND： bcr-abl fusion gene is not only diagnostic criteria of chronic myelocytic leukemia, but a only index of adjusting pathogenetic condition or curative effect. The dynamics of bcr-abl fusion gene is important for assessing outcome and prognosis of allogeneic hematopoietic stem cell transplantation. OBJECTIVE： To analyze the bcr-abl fusion gene levels in chronic myelocytic leukemia patients following allogeneic hematopoietic stem cell transplantation. DESIGN： Retrospective case analysis. PARTICIPANTS： A total of 22 chronic myelocytic leukemia patients, who underwent allogeneic hematopoietic stem cell transplantation in one year, were enrolled at the Department of Hematology, Guangdong Provincial People＇s Hospital from April 2001 to January 2007, with a median age of 31.5 years. Informed consent was obtained patients. The protocol was approved by Hospital＇s Ethics Committee. METHODS： All donors received peripheral blood stem cell mobilization using granulocyte colony-stimulating factor. Modified BU/CY combined with FLU pretreatment scheme was used in all patients. Donors and recipients who had mismatched blood type received plasma exchange at 7 and 1 days before transplantation to reduce antibody titer of blood type. Patients were injected with averagely 5.48×10^8/kg mononuclear cells of donors via deep vein, averagely 10.45×10^6/kg CD34^＋ cells. Because transplantation and follow-up time were different, 3 14 samples of peripheral blood were collected from each patient, totally 130 samples. MAIN OUTCOME MEASURES： bcr-abl transcript levels in 130 periphery blood samples from 22 chronic myelocytic leukemia patients after transplantation were detected by real-time quantitative polymerase chain reaction （PCR）. RESULTS： bcr-abl transcript levels was decreasing gradually within the first 6 months following transplantation. The proportion of patients without bcr-abl transcripts at 1, 3, and 6 months after transplantation were 33.33%, 53.33% and 84.62%, respectively. Patients with positive bcr-abl transcript at a high level （bcr-abl/abl%≥ 0.02%） accounted for 58.33% at 1 month and declined to 33.33% and 15.38% at 3 and 6 months after transplantation. While patients with positive bcr-abl transcript at low level （bcr-abl/abl%〈 0.02%） accounted for 8.33%, 13.33% and 0 at 1, 3 and 6 months after transplantation, respectively. At 6 months after transplantation, bcr-abl transcripts were undetectable in majority of patients for several times. Nine （69.23%） patients were persistently negative, one （7.69%） patient was fluctuating positive at a low level, one （7.69%） patient was persistently positive at low level, and two patients relapsed （15.38%）. The levels of bcr-abl transcripts in two relapsed patients did not reduce to 0 at 6 months after transplantation, and two of three bcr-abl results within the first six months after transplantation were positive at a high level. CONCLUSION： The overall trend of bcr-abl levels is decreasing after transplantation. But the patterns of bcr-abl transcript in different patients after allograft were variable, bcr-abl real-time quantitative PCR monitoring could help to define the change trend.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2008年第38期7407-7411,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
