非血缘脐血干细胞移植和同胞外周血干细胞移植免疫重建与慢性移植物抗宿主病的研究

OBJECTIVE: 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）. METHODS: 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. RESULTS: ① The cumulative incidence of the moderate to severe cGVHD in the UCBT group was significantly lower than that in the PBSCT group［9.38％（95％ CI 3.35％–15.02％）vs 28.57％（95％ CI 9.72％–43.50％）, P＝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％ CI 9.20％–23.60％）vs 32.10％（95％ CI 15.80％–49.70％）, P＝0.047; 10.40％（95％ CI 5.30％–17.50％）vs 28.60％（95％ CI 13.30％–46.00％）, P＝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 vs 31.40 （18.10–44.00）×10(7)/L, P<0.001; 71.30（49.60–101.45）×10(7)/L vs 41.60（25.82–56.27）×10(7)/L, P<0.001; 83.00（50.17–121.55）×10(7)/L vs 44.85（31.62–62.10）×10(7)/L, P<0.001］; the proportions of CD4(+)T cells in the UCBT group were always higher than those in the PBSCT group（P<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 vs 0.10（0–0.30）×10(7)/L, P<0.001; 0.45％（0.30％–2.20％）vs 0.20％（0.10％–0.40％）, P＝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 vs 23.35（5.07–35.00）×10(7)/L, P<0.001; 21.45（11.80–30.45）％ vs 9.00％（3.08％–16.73％）, P<0.001. 66.70（36.97–98.72）×10(7)/L vs 20.85（7.72–39.40）×10(7)/L, P<0.001; 22.20％ （14.93％–29.68％）vs 8.75％（5.80％–18.93％）, P<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 vs 0.05（0–0.84）×10(7)/L, P<0.001; 5.35％ （1.90％–12.20％）vs 1.45％（0–7.78％）, P＝0.002. 2.25（1.07–6.71）×10(7)/L vs 0.12（0–0.77）×10(7)/L, P<0.001; 6.25％（2.00％–12.33％）vs 0.80％（0–5.25％）, P<0.001. 3.69（0.83–8.66）×10(7)/L vs 0.46（0–0.93）×10(7)/L, P<0.001; 6.15％（1.63％–11.75％）vs 1.40％（0.18％–5.85％）, P<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（P＝0.038, P＝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（P＝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（P＝0.006, P＝0.028, P＝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（P＝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. CONCLUSION: 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.