Wang J, Pan T Z, Huang P P, Sun Z M, Zhu H P
The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) , Hefei 230001, China.
The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) , Hefei 230001, China Institute of Blood and Cell Therapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China.
Zhonghua Xue Ye Xue Za Zhi. 2021 Jun 14;42(6):466-473. doi: 10.3760/cma.j.issn.0253-2727.2021.06.005.
To explore the relationship between the reconstitution of immune cells in patients with hematological malignancies and the occurrence of chronic graft-versus-host disease (cGVHD) after treatment with unrelated cord blood transplantation (UCBT) and sibling peripheral blood stem cell transplantation (PBSCT) . A total of 124 patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) in the First Affiliated Hospital of University of Science and Technology of China from March 2018 to August 2019, including 96 patients with UCBT and 28 patients with PBSCT. Peripheral blood immune cells of patients with UCBT and PBSCT were detected at 1, 3, 6, 9, and 12 months after transplantation using flow cytometry, and both UCBT and PBSCT patients were divided into cGVHD and non-cGVHD groups based on whether cGVHD occurred to explore the correlation between the immune cells reconstitution of the two types of transplantation and cGVHD. ①The cumulative incidence of the moderate to severe cGVHD in the UCBT group was significantly lower than that in the PBSCT group[9.38% (95% 3.35%-15.02%) 28.57% (95% 9.72%-43.50%) , =0.008]; the 2-year cumulative incidence of cGVHD and moderate to severe cGVHD in the UCBT group was lower than that in the PBSCT group[15.60% (95% 9.20%-23.60%) 32.10% (95% 15.80%-49.70%) , =0.047; 10.40% (95% 5.30%-17.50%) 28.60% (95% 13.30%-46.00%) , =0.014]. ②The absolute counts of CD4(+)T cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[59.00 (36.70-89.65) ×10(7)/L 31.40 (18.10-44.00) ×10(7)/L, <0.001; 71.30 (49.60-101.45) ×10(7)/L 41.60 (25.82-56.27) ×10(7)/L, <0.001; 83.00 (50.17-121.55) ×10(7)/L 44.85 (31.62-62.10) ×10(7)/L, <0.001]; the proportions of CD4(+)T cells in the UCBT group were always higher than those in the PBSCT group (<0.05) . The absolute counts and proportions of B cells in the PBSCT group were higher than those in the UCBT group at the first month after transplantation[0.70 (0.30-1.70) ×10(7)/L 0.10 (0-0.30) ×10(7)/L, <0.001; 0.45% (0.30%-2.20%) 0.20% (0.10%-0.40%) , =0.002]; the absolute counts and proportions of B cells in the UCBT group were higher than those in the PBSCT group at 9 and 12 months after transplantation[53.80 (28.00-103.20) ×10(7)/L 23.35 (5.07-35.00) ×10(7)/L, <0.001; 21.45 (11.80-30.45) % 9.00% (3.08%-16.73%) , <0.001. 66.70 (36.97-98.72) ×10(7)/L 20.85 (7.72-39.40) ×10(7)/L, <0.001; 22.20% (14.93%-29.68%) 8.75% (5.80%-18.93%) , <0.001]. The absolute counts and proportions of regulatory B (Breg) cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[1.23 (0.38-3.52) ×10(7)/L 0.05 (0-0.84) ×10(7)/L, <0.001; 5.35% (1.90%-12.20%) 1.45% (0-7.78%) , =0.002. 2.25 (1.07-6.71) ×10(7)/L 0.12 (0-0.77) ×10(7)/L, <0.001; 6.25% (2.00%-12.33%) 0.80% (0-5.25%) , <0.001. 3.69 (0.83-8.66) ×10(7)/L 0.46 (0-0.93) ×10(7)/L, <0.001; 6.15% (1.63%-11.75%) 1.40% (0.18%-5.85%) , <0.001].The absolute counts and proportions of CD3(+)T cells, CD8(+)T cells, and Treg cells in the UCBT group were not significantly different from those in the PBSCT group. ③The absolute counts of B cells in the non-cGVHD group of UCBT patients were higher than those in the moderate to severe cGVHD group at 6 and 12 months after transplantation (=0.038, =0.043) ; the proportions of B cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 6 months after transplantation (=0.049) . The absolute counts of Breg cells in the non-cGVHD group of patients with UCBT were higher than those in the moderate to severe cGVHD group at 6, 9, and 12 months after transplantation (=0.006, =0.028, =0.050) ; the proportions of Breg cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 9 months after transplantation (=0.038) . ④The absolute counts and proportions of B and Breg cells in the non-cGVHD group of patients with PBSCT were not statistically different than those in the moderate to severe cGVHD group. In the process of immune cell reconstitution, the Breg cells in the UCBT group were higher than those in the PBSCT group, and the Breg cells in the non-cGVHD group of the two types of transplantation were always higher than those in the moderate to severe cGVHD group, indicating that Breg cells can reduce the occurrence of cGVHD, revealing the possible reason for the lower incidence of cGVHD in the UCBT group.
探讨血液系统恶性肿瘤患者免疫细胞重建与非亲缘脐血移植（UCBT）及同胞外周血干细胞移植（PBSCT）治疗后慢性移植物抗宿主病（cGVHD）发生之间的关系。选取2018年3月至2019年8月在中国科学技术大学附属第一医院接受异基因造血干细胞移植（allo-HSCT）的124例患者，其中UCBT患者96例，PBSCT患者28例。采用流式细胞术检测UCBT和PBSCT患者移植后1、3、6、9和12个月外周血免疫细胞，并根据是否发生cGVHD将UCBT和PBSCT患者分为cGVHD组和非cGVHD组，探讨两种移植方式免疫细胞重建与cGVHD的相关性。①UCBT组中重度cGVHD的累积发生率显著低于PBSCT组[9.38%（95% 3.35%-15.02%） 28.57%（95% 9.72%-43.50%）， =0.008]；UCBT组cGVHD及中重度cGVHD的2年累积发生率低于PBSCT组[15.60%（95% 9.20%-23.60%） 32.10%（95% 15.80%-49.70%）， =0.047；10.40%（95% 5.30%-17.50%） 28.60%（95% 13.30%-46.00%）， =0.014]。②移植后6、9和12个月，UCBT组CD4(+)T细胞的绝对计数高于PBSCT组[59.00（36.70-89.65）×10(7)/L 31.40（18.10-44.00）×10(7)/L，<0.001；71.30（49.60-101.45）×10(7)/L 41.60（25.82-56.27）×10(7)/L，<0.001；83.00（50.17-121.55）×10(7)/L 44.85（31.62-62.10）×10(7)/L，<0.001]；UCBT组CD4(+)T细胞的比例始终高于PBSCT组（<0.05）。移植后第1个月PBSCT组B细胞的绝对计数和比例高于UCBT组[0.70（0.30-1.70）×10(7)/L 0.10（0-0.30）×10(7)/L，<0.001；0.45%（0.30%-2.20%） 0.20%（0.10%-0.40%）， =0.002]；移植后9和12个月UCBT组B细胞的绝对计数和比例高于PBSCT组[53.80（28.00-103.20）×10(7)/L 23.35（5.07-35.00）×10(7)/L，<0.001；21.45（11.80-30.45）% 9.00%（3.08%-16.73%），<0.001。66.70（36.97-98.72）×10(7)/L 20.85（7.72-39.40）×10(7)/L，<0.001；22.20%（14.93%-29.68%） 8.75%（5.80%-18.93%），<0.001]。移植后6、9和12个月UCBT组调节性B（Breg）细胞的绝对计数和比例高于PBSCT组[1.23（0.38-3.52）×10(7)/L 0.05（0-0.84）×10(7)/L，<0.001；5.35%（1.90%-12.20%） 1.45%（0-7.78%）， =0.002。2.25（1.07-6.71）×10(7)/L 0.12（0-0.77）×10(7)/L，<0.001；6.25%（2.00%-12.33%） 0.80%（0-5.25%），<0.001。3.69（0.83-8.66）×10(7)/L 0.46（0-0.93）×10(7)/L，<0.001；6.15%（1.63%-11.75%） 1.40%（0.18%-5.85%），<0.001]。UCBT组CD3(+)T细胞、CD8(+)T细胞和调节性T细胞（Treg）的绝对计数和比例与PBSCT组无显著差异。③UCBT患者非cGVHD组移植后6和12个月B细胞的绝对计数高于中重度cGVHD组（ =0.038， =0.043）；移植后6个月非cGVHD组B细胞的比例高于中重度cGVHD组（ =0.049）。UCBT患者非cGVHD组移植后6、9和12个月Breg细胞的绝对计数高于中重度cGVHD组（ =0.006， =0.028， =0.050）；移植后9个月非cGVHD组Breg细胞的比例高于中重度cGVHD组（ =0.038）。④PBSCT患者非cGVHD组B和Breg细胞的绝对计数和比例与中重度cGVHD组无统计学差异。在免疫细胞重建过程中，UCBT组Breg细胞高于PBSCT组，两种移植方式非cGVHD组的Breg细胞始终高于中重度cGVHD组，提示Breg细胞可降低cGVHD的发生，揭示了UCBT组cGVHD发生率较低的可能原因。
