Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT
Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT
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DOI：
10.1038/sj.bmt.1701119
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发表时间：
1998-03-01
影响因子：
4.8
通讯作者：
Klingebiel, T
中科院分区：
文献类型：
--
作者：
Bader, P;Beck, J;Klingebiel, T
在一项前瞻性研究中，我们分析了55例急性白血病患者外周血中的造血嵌合体（ALL 21例，AML 20例，MDS 14例），中位年龄为13.5岁，在同种异体骨髓移植后的极短时间间隔内（allo-BMT），本研究旨在确定混合造血嵌合体（MC）的意义关于allo-BMT后急性白血病患者的临床结果，通过可变数目串联重复（VNTR）序列的PCR进行嵌合体分析，最大灵敏度为0.8%，13名男性患者移植了一名女性捐赠者的骨髓，也通过扩增Y染色体特异性α重复序列进行了研究（0.1-0.01%灵敏度），55例患者的VNTR分析显示36例完全嵌合（CC），18例随访MC和1例自体恢复，MC的定量分析确定了10/18例自体模式增加的患者，其中9/10例随后复发，自体恢复的患者也复发，18例MC患者中有8例显示自体DNA量减少，并在进一步随访时成为CC。相比之下，在先前的嵌合状态分析中，只有7/36例CC患者复发，然而，在4/7例患者中，最后一次CC确认与复发之间的间隔超过4个月，在2/7例患者中，在外周血中但在骨髓抽吸物中未检测到自体DNA，这7例患者中的1例在3周内发生暴发性复发。CC患者的无复发生存概率为0.67（It = 36），MC 1.0降低的患者（n = 8）和MC 0.1增加的患者（n = 10）。结果表明，通过PCR以短时间间隔进行的连续和定量嵌合分析为早期检测潜在疾病的复发提供了可靠和快速的筛选方法，因此是鉴定复发风险最高的患者的预后工具。
Within a prospective study we analyzed hematopoietic chimerism in serial peripheral blood samples taken from 55 patients with acute leukemias (ALL 21, AML 20, MDS 14) with a median age of 13.5 years at very short time intervals following allogeneic bone marrow transplantation (allo-BMT), The investigation was performed to determine the implications of mixed hematopoietic chimerism (MC) with regard to the clinical outcome in patients with acute leukemias after allo-BMT, Analysis of chimerism was performed by PCR of variable number of tandem repeat (VNTR) sequences with a maximum sensitivity of 0.8%, Thirteen male patients transplanted with the marrow of a female donor were also studied by amplification of a Y-chromosome-specific alphoid repeat (0.1-0.01% sensitivity), VNTR analysis in 55 patients revealed complete chimerism (CC) in 36 cases, MC in 18 follow-ups and autologous recovery in one patient, Quantitative analysis of MC identified 10/18 patients with increasing autologous patterns in whom 9/10 subsequently relapsed, The patient with autologous recovery relapsed as well, Eight of 18 patients with MC showed decreasing amounts of autologous DNA and became CC upon further follow-up, In contrast, only 7/36 patients with CC in the prior analysis of chimerism status relapsed, However, in 4/7 patients the interval between last CC confirmation and relapse was more than 4 months, In 2/7 patients autologous DNA was not detectable in peripheral blood but in bone marrow aspirates, One of these seven patients developed a fulminant relapse within 3 weeks, The probability of relapse-free survival for patients with CC is 0.67 (It = 36), for patients with decreasing MC 1.0 (n = 8) and for patients with increasing MC 0.1 (n = 10), In summary, the results demonstrate that serial and quantitative chimerism analysis at short time intervals by PCR provides a reliable and rapid screening method for the early detection of recurrence of underlying disease and is therefore a prognostic tool to identify patients at highest risk of relapse.