Incidence, Risk Factors, and Outcomes of Chronic Graft-versus-Host Disease in Pediatric Patients with Hematologic Malignancies after T Cell-Replete Myeloablative Haploidentical Hematopoietic Stem Cell Transplantation with Antithymocyte Globulin/Granulocyt
Incidence, Risk Factors, and Outcomes of Chronic Graft-versus-Host Disease in Pediatric Patients with Hematologic Malignancies after T Cell-Replete Myeloablative Haploidentical Hematopoietic Stem Cell Transplantation with Antithymocyte Globulin/Granulocyt
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患有血液系统恶性肿瘤的儿科患者在使用抗胸腺细胞球蛋白/粒细胞进行 T 细胞清髓性单倍相合造血干细胞移植后慢性移植物抗宿主病的发病率、危险因素和结果
DOI：
10.1016/j.bbmt.2020.05.021
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发表时间：
2020
影响因子：
4.3
通讯作者：
Wang Yu
中科院分区：
文献类型：
--
作者：
Tang Fei-Fei;Cheng Yi-Fei;Xu Lan-Ping;Zhang Xiao-Hui;Yan Chen-Hua;Han Wei;Chen Yu-Hong;Huang Xiao-Jun;Wang Yu
在使用抗胸腺细胞球蛋白（ATG）/粒细胞集落刺激因子（G-CSF）的T细胞完全（TCR）清髓性单倍体相合造血干细胞移植（haplo-HSCT）后，血液系统恶性肿瘤儿科患者发生慢性移植物抗宿主病（cGVHD）的具体描述、风险因素和结局尚未得到充分描述。我们回顾性分析了2015年1月至2017年12月期间292例连续儿童恶性血液病患者在采用ATG/G-CSF进行TCR清髓性haplo-HSCT后，根据2014年美国国立卫生研究院共识标准（NIH-CC）记录的cGVHD的发生率、风险因素和结局。共有170例患者经历了cGVHD。总cGVHD和轻度、中度和重度cGVHD的3年累积发生率分别为57.9%、27.5%、18.8%和11.9%。多因素分析显示，急性GVHD（aGVHD）II-IV级（风险比，1.578;P= 0.002）是cGVHD的独立危险因素。与无cGVHD患者相比，cGVHD患者3年复发率较低（17.6%对27.2%;P= .009），相似的3年非复发死亡率（NRM）（5.9%对5.4%;P= 0.79），以及更好的3年无病生存率（DFS）（77.8%对66.9%;P= 0.007）和总生存期（OS）（81.3%对68.6%;P= 0.001），尤其是轻度或中度cGVHD患者;然而，未观察到重度cGVHD对复发、NRM、DFS或OS的显著影响。总之，在患有血液恶性肿瘤的儿科患者中，采用ATG/G-CSF进行TCR清髓性haplo-HSCT后，重度cGVHD的发生率是可以接受的。既往aGVHD II-IV级是发生cGVHD的危险因素。只有轻度或中度cGVHD与较低的复发风险相关，在采用ATG/G-CSF的TCR清髓性haplo-HSCT后，转化为血液恶性肿瘤儿科患者的DFS和OS改善。
The specific description, risk factors, and outcomes of chronic graft-versus-host disease (cGVHD) in pediatric patients with hematologic malignancies after T cell-replete (TCR) myeloablative haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with antithymocyte globulin (ATG)/granulocyte colony-stimulating factor (G-CSF) have not been previously well described. We retrospectively analyzed the incidence, risk factors, and outcomes of cGVHD documented according to the 2014 National Institutes of Health consensus criteria (NIH-CC) in 292 consecutive pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF between January 2015 and December 2017. A total of 170 patients experienced cGVHD. The 3-year cumulative incidence of total cGVHD and mild, moderate, and severe cGVHD was 57.9%, 27.5%, 18.8%, and 11.9%, respectively. Multivariate analysis showed that acute GVHD (aGVHD) grade II-IV (hazard ratio, 1.578;P= .002) was an independent risk factor for cGVHD. Compared to patients without cGVHD, patients with cGVHD demonstrated a lower 3-year relapse (17.6% versus 27.2%;P= .009), a similar 3-year nonrelapse mortality (NRM) (5.9% versus 5.4%;P= .79), and better 3-year disease-free survival (DFS) (77.8% versus 66.9%;P= .007) and overall survival (OS) (81.3% versus 68.6%;P= .001), particularly those with mild or moderate cGVHD; however, no significant impact of severe cGVHD on relapse, NRM, DFS, or OS was seen. In conclusion, the incidence of severe cGVHD in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF was acceptable. Previous aGVHD grade II-IV was a risk factor for the occurrence of cGVHD. Only mild or moderate cGVHD was associated with a lower risk of relapse, translating into improved DFS and OS in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF.