Characterization of lineage-specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse
Characterization of lineage-specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse
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DOI：
10.1046/j.1365-2141.2000.01927.x
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发表时间：
2000-03-01
影响因子：
6.5
通讯作者：
Klingebiel, T
中科院分区：
文献类型：
--
作者：
Bader, P;Stoll, K;Klingebiel, T
最近，我们已经表明，急性白血病和骨髓增生异常综合征（MDS）的患者，谁表现出增加的混合嵌合体（MC）移植后的系列PCR分析，复发的风险显着增加。为了确定这些患者中MC的增加是否是由正常受体的再现引起的：造血或恶性细胞的再现，我们纯化了不同的白细胞亚群，并通过基于PCR的方法分析了这些亚组分的供体-受体比例，用于分析小卫星DNA区域。在14例患者中[8例急性淋巴细胞白血病（ALL），3例急性髓细胞白血病（AML）和3例MDS]，当外周血系列分析首次发现MC增加时，对亚组分进行了分析。在这14个病人中的7个在所有14例MC增加的患者中，在不同的单核细胞亚群中检测到受体细胞。在坦率复发期间表征的患者中，发现两种不同的分布模式。结果显示，除了不同单核细胞亚群中的原始细胞群以及粒细胞外，急性淋巴细胞白血病（ALL）、急性髓细胞白血病（AML）和骨髓增生异常综合征（MDS）各1例。在急性白血病患者谁复发后+300天（两个ALL和一个AML），只有白血病细胞被发现是受者的起源，而所有其他造血细胞系的供体derived.These数据表明，在移植后早期持续MC主要是由正常的受者造血细胞。这一发现进一步支持了这样的假设，即混合造血嵌合状态可能会降低急性白血病和MDS患者同种异体反应性供体衍生效应细胞的临床移植物抗白血病（GVL）效应，从而促进可能在制备方案中存活的残留恶性细胞的增殖。
Recently, we have shown that patients with acute leukaemias and myelodysplastic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon serial PCR analysis after transplant, have a significantly increased risk of relapse. To determine whether the increasing MC in these patients is caused by the reappearance of normal recipient: haematopoiesis or by the reoccurrence of malignant cells, we purified different leucocyte subpopulations and analysed these subfractions with regard to their donor-recipient ratio by a PCR-based method for the analysis of minisatellite DNA regions. In 14 patients [eight acute lymphoblastic leukaemia (ALL), three acute myelogenous leukaemia (AML) and three MDS] subfractions were analysed when increasing MC was first noted upon serial analysis of the peripheral blood. In seven of these 14 patients (four ALL, two AML and one MDS), subfractions were characterized at the time of frank haematological relapse, In all 14 patients investigated with increasing MC, recipient cells were detected in different mononuclear cell subpopulations, In patients characterized during frank relapse, two distinct distribution patterns were found. Patients who relapsed before day +300 (one ALL, two AML and one MDS) showed recipient-derived (normal) cells in addition to blast populations in different mononuclear subsets as well as granulocytes. In patients with acute leukaemias who relapsed after day +300 (two ALL and one AML), only leukaemic cells were found that were of recipient origin, whereas all other haematopoietic cell lines were donor derived.These data show that persistent MC in the early posttransplant period is caused predominantly by normal recipient haematopoietic cells. This finding further supports the hypothesis that a state of mixed haematopoietic chimaerism may reduce the clinical graft-versus-leukaemia (GVL) effect of alloreactive donor-derived effector cells in patients with acute leukaemias and MDS, and thus facilitate the proliferation of residual malignant cells that may have survived the preparative regimen.