Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China; Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, Beijing, China.
Biol Blood Marrow Transplant. 2020 Sep;26(9):1655-1662. doi: 10.1016/j.bbmt.2020.05.021. Epub 2020 Jun 3.
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.
在接受抗胸腺细胞球蛋白（ATG）/粒细胞集落刺激因子（G-CSF）的 T 细胞充足（TCR）清髓性单倍体造血干细胞移植（haplo-HSCT）后，儿科血液恶性肿瘤患者慢性移植物抗宿主病（cGVHD）的具体描述、危险因素和结局尚未得到很好的描述。我们回顾性分析了 2015 年 1 月至 2017 年 12 月期间，292 例接受 TCR 清髓性 haplo-HSCT 联合 ATG/G-CSF 的血液恶性肿瘤儿科患者中，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、危险因素和结局。共有 170 例患者发生 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，急性移植物抗宿主病（aGVHD）Ⅱ-Ⅳ级（风险比，1.578；P =.002）是 cGVHD 的独立危险因素。与无 cGVHD 的患者相比，有 cGVHD 的患者 3 年复发率较低（17.6%比 27.2%；P =.009），3 年非复发死亡率（NRM）相似（5.9%比 5.4%；P =.79），3 年无病生存率（DFS）较好（77.8%比 66.9%；P =.007）和总生存率（OS）（81.3%比 68.6%；P =.001），尤其是轻度或中度 cGVHD；然而，严重 cGVHD 对复发、NRM、DFS 或 OS 没有显著影响。总之，在接受 ATG/G-CSF 的 TCR 清髓性 haplo-HSCT 后，儿科血液恶性肿瘤患者中严重 cGVHD 的发生率是可以接受的。既往 aGVHD Ⅱ-Ⅳ 级是 cGVHD 发生的危险因素。只有轻度或中度 cGVHD 与较低的复发风险相关，这转化为 TCR 清髓性 haplo-HSCT 联合 ATG/G-CSF 治疗后儿科血液恶性肿瘤患者的 DFS 和 OS 改善。
