多种免疫抑制剂联合应用于单倍体骨髓移植

Immune-reconstitution following HLA haplotype related T-cell undepleted allogeneic bone marrow transplantation

目的 :观察多种免疫抑制剂联合使用后半相合未去T细胞骨髓移植术后患者免疫功能的恢复情况。方法 :38例白血病患者接受HLA 2～ 3个位点不匹配的亲缘骨髓移植 ,用ATG、CD2 5抗体、CSA、MTX、MMF预防移植物抗宿主病 (GVHD) ,定期对受者在移植术后 1、3、6、12、18个月的外周血淋巴细胞亚群和血清免疫球蛋白进行检测。结果 :移植术后 1个月患者淋巴细胞各亚群均明显下降 ,CD4 + T最明显 ,CD4 + T细胞绝对数在 +6月达 2 0 0个 /μl,导致CD4 /CD8持续倒置 ,在移植后 18个月才逐渐恢复。CD3+ 、CD8+ 、CD19+ B细胞计数在BMT后的 6～ 12个月基本恢复。因常规输注丙种球蛋白BMT后IgG一直正常 ,IgM和IgA分别在移植后 6～ 9个月和 18个月恢复。结论 :单倍体相合骨髓移植后 1年患者免疫功能处于低下状态 ,CD4 + T和IgA恢复最慢 ,CD4 + 细胞百分比和绝对值持续的低下 ,CD4 /CD8持续倒置是移植后感染高发的原因 。

Objective:To evaluated immune state of the patients after using several immunosuppressive drugs to reduce acute GVHD in T-cell undepleted haploidentical bone marrow transplantation (Allo-BMT).Method:Thirty-eight patients with leukemia received Allo-BMT from HLA two or three loci mismatched related donors, ATG, CD25 monoclonal antibody, CsA, MTX, and mycophenolate mofetil (MMF) were combined for GVHD prophylaxis. Using Flow cytometry (FCM) to detect lymphocyte subsets and to detect the level of Ig of some recipients at 1, 3, 6, 12, 18 months after BMT.Result:All lymphocyte subsets counts were significantly decreased in the first month after BMT, CD4 + T cell were lower significantly throughout the 18 months post-BMT, the absolute number of CD4 + T cell count reached to 200/ul at 6 months post-BMT, and CD4/CD8 ratios persistently reversed at 18 months after BMT. CD8 +T cell, CD3 + cell and CD19 +B cell counts recovered at 6～12 months after BMT. With regular IV Ig, the serum levels of IgG were normal post-BMT, the levels of IgM and IgA reached to normal level at 6～9 months and 18 months respectively after BMT.Conclusion:The recipents remained immunodeficiency throughout 1 years post HLA haplotype match and T-cell undepleted Allo-BMT. CD4 +T cell and IgA recovered significantly slowly, especially the percent and the absolute number of CD4 +T cell were lower significantly throughout the 18 months post-BMT, persistently CD4/CD8 ratios reversed at 18 months following BMT. It maybe cause high-risk infectons. It is important to give patient support care.