Mixed Hematologic Chimerism After Allogeneic Marrow Transplantation for Severe Aplastic Anemia Is Associated With a Higher Risk of Graft Rejection and a Lessened Incidence of Acute Graft-Versus-Host Disease
Mixed Hematologic Chimerism After Allogeneic Marrow Transplantation for Severe Aplastic Anemia Is Associated With a Higher Risk of Graft Rejection and a Lessened Incidence of Acute Graft-Versus-Host Disease
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严重再生障碍性贫血同种异体骨髓移植后的混合血液嵌合现象与移植物排斥风险较高和急性移植物抗宿主病发病率降低相关
DOI：
10.1182/blood.v67.3.811.bloodjournal673811
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发表时间：
1986
期刊：
影响因子：
20.3
通讯作者：
Thomas Ed
中科院分区：
文献类型：
--
作者：
R. Hill;F. Petersen;R. Storb;Appelbaum Fr;K. Doney;S. Dahlberg;Ramberg Re;Thomas Ed
96例接受性别不匹配、HLA相同的异基因同胞骨髓移植的重度再生障碍性贫血患者进行了连续的细胞遗传学分析，以确定移植后混合血液学嵌合体的发生率和意义。在96例患者中，56例（58.3%）在移植后14天或以后的外周血或骨髓中检测到宿主和供体细胞共存的混合嵌合体，40例（41.7%）为100%供体型造血细胞的完全嵌合体。混合嵌合体的发生率与既往输血和输注供体血沉棕黄层无关。在混合嵌合体组中，排斥率显著增加，特别是在未接受血沉棕黄层的患者中（36例排斥中有14例），尽管总体而言，大多数（69.7%）保留了他们的第一次移植。排斥反应几乎仅见于移植前多次输血的患者。如果对第一次移植排斥的患者进行删失，混合嵌合体患者II级至IV级急性移植物抗宿主病（GVHD）的总体发生率显著降低。特别是具有混合嵌合体的输血患者不太可能发展为II级至IV级急性GVHD。慢性GVHD的发生率在两组中相似，对生存率没有显著影响。在这项研究中，混合嵌合体在移植后持续长达395天，第一次移植物被排斥，或者更常见的是，造血恢复为100%的供体型细胞。再生障碍性贫血患者在造血恢复为供者细胞类型之前接受了匹配的异基因骨髓移植，混合淋巴造血嵌合体可能持续很长时间。
Ninety-six patients with severe aplastic anemia who received a sex- mismatched, HLA-identical allogeneic sibling marrow transplant had sequential cytogenetic analyses performed to determine the incidence and implications of posttransplant mixed hematologic chimerism. Of the 96 patients, 56 (58.3%) became mixed chimeras with coexisting host and donor cells detected in peripheral blood or marrow 14 days or later after transplant, and 40 patients (41.7%) were complete chimeras with 100% donor-type hematopoietic cells. The incidence of mixed chimerism was independent of prior blood production transfusions and infusion of donor buffy coat. The rejection rate was significantly increased in the mixed chimeric group, particularly in patients not receiving buffy coat (14 of 36 rejecting), although overall, the majority (69.7%) retained their first graft. Rejection was seen almost exclusively in patients exposed to multiple transfusions before transplantation. If patients who reject their first graft are censored, the overall incidence of grades II through IV acute graft-v-host disease (GVHD) was significantly reduced in those with mixed chimerism. Transfused patients with mixed chimerism in particular were less likely to develop grades II through IV acute GVHD. The incidence of chronic GVHD was similar in the two groups and did not significantly influence survival. In this study, mixed chimerism persisted for up to 395 days posttransplant, either the first graft being rejected or, more commonly, hematopoiesis reverting to 100% donor-type cells. Mixed lymphohematopoietic chimerism may persist in patients with aplastic anemia who have received matched allogeneic marrow transplants for significant periods before hematopoiesis reverts to donor cell type.