Nadaf Rubiya, Lee Helena, Bonney Denise, Hanasoge-Nataraj Ramya, Senthil Srividhya, Horgan Claire, Guiver Malcolm, Poulton Kay, Wynn Robert
Departments of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
Departments of Transplantation Laboratories, Manchester Royal Infirmary, Manchester M13 9WL, UK.
Cells. 2024 Dec 20;13(24):2119. doi: 10.3390/cells13242119.
Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC from HLA-matched donors for non-malignant diseases, whose pre-transplant conditioning therapy included alemtuzumab and who were monitored with lineage-specific chimerism after transplant. At 6 years post-transplant, overall survival (OS) was 91.1% and event-free survival (EFS) was 81.5%, with no grade III-IV acute GvHD or chronic GVHD observed. Recipient T-cells did not contribute to graft loss. Mixed T-cell chimerism (MC) did not affect EFS, and there was no connection between T-cell chimerism and myeloid chimerism in patients with MC or graft loss. MC significantly correlated with virus infection; more children with MC were CMV seropositive than those with complete chimerism (CC). Additionally, MC was more common in patients with CMV viramia post-transplant. CD8 T-cell reconstitution was affected by viral reactivation, including CMV, with CD8 T-cell counts higher in the MC group than in the CC group. Mixed T-cell chimerism is due to autologous, virus-specific, predominantly CD8, T-cell expansion, and is protective and not deleterious to the recipient.
在评估异基因造血干细胞移植(HCT)后的移植物功能时,髓系嵌合比全血嵌合更能反映供体干细胞植入情况。我们描述了130例18岁以下患者的经验,这些患者接受了异基因HCT治疗,使用来自HLA匹配供体的骨髓或外周血干细胞治疗非恶性疾病,其移植前预处理包括阿仑单抗,移植后采用谱系特异性嵌合进行监测。移植后6年,总生存率(OS)为91.1%,无事件生存率(EFS)为81.5%,未观察到III-IV级急性移植物抗宿主病(GvHD)或慢性移植物抗宿主病(GVHD)。受者T细胞对移植物丢失无影响。混合T细胞嵌合(MC)不影响EFS,在有MC或移植物丢失的患者中,T细胞嵌合与髓系嵌合之间无关联。MC与病毒感染显著相关;与完全嵌合(CC)的儿童相比,更多有MC的儿童巨细胞病毒(CMV)血清学呈阳性。此外,MC在移植后发生CMV病毒血症的患者中更常见。病毒再激活,包括CMV,影响CD8 T细胞重建,MC组的CD8 T细胞计数高于CC组。混合T细胞嵌合是由于自体、病毒特异性、主要为CD8的T细胞扩增所致,对受者具有保护作用而非有害作用。