复发慢性粒细胞白血病患者T细胞和树突状细胞嵌合状态的动态变化及其对供体淋巴细胞输注后同种异体反应性诱导的影响。
Dynamics in chimerism of T cells and dendritic cells in relapsed CML patients and the influence on the induction of alloreactivity following donor lymphocyte infusion.
作者信息
Levenga H, Woestenenk R, Schattenberg A V, Maas F, Jansen J H, Raymakers R, De Mulder P H M, van de Wiel-van Kemenade E, Schaap N, de Witte T, Dolstra H
机构信息
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
出版信息
Bone Marrow Transplant. 2007 Sep;40(6):585-92. doi: 10.1038/sj.bmt.1705777. Epub 2007 Jul 16.
Donor lymphocyte infusion (DLI) after allogeneic SCT induces complete remissions in approximately 80% of patients with relapsed CML in chronic phase, but some patients do not respond to DLI. We studied absolute numbers of dendritic cell (DC) subsets and chimerism in T cells and two subsets of blood DCs (myeloid DCs (MDCs) and plasmacytoid DCs (PDCs)) in relation to DLI-induced alloreactivity. Based on T cell and DC chimerism, we identified three groups. Four patients were completely donor chimeric in T cells and DC subsets. These patients had an early stage of relapse, and three of the four patients attained complete molecular remission (CMolR) without significant GVHD. Six patients were completely donor in T cells and mixed chimeric in DC subsets. All patients entered CMolR, but this was associated with GVHD in four and cytopenia in three patients. Five patients had mixed chimerism in T cells and complete recipient chimerism in MDC; only two patients entered CMolR. Our data suggest that the combination of donor T cells and mixed chimerism in DC subsets induces a potent graft-versus-leukemia (GVL) effect in association with GVHD. DLI in patients with an early relapse and donor chimerism in both T cells and DC subsets results in GVL reactivity without GVHD.
异基因造血干细胞移植(SCT)后进行供体淋巴细胞输注(DLI)可使约80%的慢性期复发慢性粒细胞白血病(CML)患者获得完全缓解,但部分患者对DLI无反应。我们研究了树突状细胞(DC)亚群的绝对数量以及T细胞和血液中两个DC亚群(髓样DC(MDC)和浆细胞样DC(pDC))的嵌合情况与DLI诱导的同种异体反应性之间的关系。基于T细胞和DC嵌合情况,我们确定了三组。4例患者的T细胞和DC亚群完全为供体嵌合。这些患者处于复发早期,4例患者中有3例在无明显移植物抗宿主病(GVHD)的情况下达到完全分子缓解(CMolR)。6例患者的T细胞完全为供体嵌合,DC亚群为混合嵌合。所有患者均进入CMolR,但这与4例患者发生GVHD以及3例患者出现血细胞减少有关。5例患者的T细胞为混合嵌合,MDC为完全受者嵌合;只有2例患者进入CMolR。我们的数据表明,供体T细胞与DC亚群的混合嵌合相结合可诱导一种与GVHD相关的强大移植物抗白血病(GVL)效应。早期复发且T细胞和DC亚群均存在供体嵌合的患者进行DLI可产生无GVHD的GVL反应。