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接受使用去除CD3/CD19移植物的单倍体相合亲属异基因移植的儿科患者的预后因素及结局

Prognostic factors and outcomes for pediatric patients receiving an haploidentical relative allogeneic transplant using CD3/CD19-depleted grafts.

作者信息

Diaz M A, Pérez-Martínez A, Herrero B, Deltoro N, Martinez I, Ramirez M, Abad L, Sevilla J, Merino E, Ruiz J, Vicario J L, Gonzalez-Vicent M

机构信息

Hematopoietic Stem Cell Transplantation Unit, Pediatric Department, Children's University Hospital Niño Jesús, Madrid, Spain.

Pediatric Hemato-Oncology and Hematopoietic Stem Cell Transplantation Unit, Pediatric Department, University Hospital La Paz, Madrid, Spain.

出版信息

Bone Marrow Transplant. 2016 Sep;51(9):1211-6. doi: 10.1038/bmt.2016.101. Epub 2016 Apr 18.

Abstract

Haploidentical hematopoietic stem cell transplantation using T-cell-depleted grafts is a valid option for pediatric patients with hematological malignancies in need of an allogeneic transplantation and lacking an HLA-identical donor. Seventy-five transplantations were performed in 70 patients. Thirty-eight patients had ALL, 32 had AML, 3 had advanced myelodysplastic syndromes and 2 juvenile myelomonocytic leukemia; 19 were in first CR, 30 in second CR, 12 in greater than second CR and 14 were considered to be in refractory disease at time of transplantation. Four patients developed graft failure. Among engrafted patients, the median time to neutrophil and platelet recovery was 13 (range 8-20) and 10 days (range 8-70), respectively. In 64 (85%) cases, ⩾1 infections were diagnosed after transplant. The probability of nonrelapse mortality by day +100 after transplantation was 10±4%. With a median follow-up of 22 months, the probability of relapse was 32±6% and disease-free survival was 52±6%. Haploidentical transplantation using CD3/CD19 depletion is associated with encouraging results especially in patients in early phase of disease. Killer-cell Ig-like receptor B haplotype donors confer a rapid natural killer cells expansion early after transplantation, resulting in lower probability of relapse and suggesting a GvL effect apart from graft-versus-host reactions. Donor infusion of high numbers of CD34+ cells is recommended in order to improve T-cell reconstitution.

摘要

使用去除T细胞移植物的单倍体相合造血干细胞移植,对于需要进行异基因移植且缺乏HLA相合供者的血液系统恶性肿瘤患儿来说是一种有效的选择。对70例患者进行了75次移植。38例患者患有急性淋巴细胞白血病(ALL),32例患有急性髓细胞白血病(AML),3例患有晚期骨髓增生异常综合征,2例患有青少年型骨髓单核细胞白血病;19例处于首次完全缓解(CR)期,30例处于第二次CR期,12例处于第二次CR期以上,14例在移植时被认为处于难治性疾病状态。4例患者发生移植物失败。在植入的患者中,中性粒细胞和血小板恢复的中位时间分别为13天(范围8 - 20天)和10天(范围8 - 70天)。64例(85%)患者在移植后诊断出≥1次感染。移植后第100天的非复发死亡率为10±4%。中位随访22个月,复发概率为32±6%,无病生存率为52±6%。使用去除CD3/CD19的单倍体相合移植取得了令人鼓舞的结果,尤其是在疾病早期的患者中。杀伤细胞免疫球蛋白样受体B单倍型供者在移植后早期可使自然杀伤细胞快速扩增,从而降低复发概率,并提示除移植物抗宿主反应外还存在移植物抗肿瘤(GvL)效应。建议输注大量供者CD34+细胞以改善T细胞重建。

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