高危和标危Ph阴性急性淋巴细胞白血病非体外去T细胞单倍型造血干细胞移植后早期免疫重建的比较研究

Comparison of immune reconstitution at early stage after unmanipulated haploidentical stem cell transplantation between high- and standard- risk Philadelphia chromosome- negative acute lymphoblastic leukemia patients in CR1

目的比较费城染色体（Ph）阴性急性淋巴细胞白血病（ALL）第1次完全缓解期（CR1）高危组与标危组患者非体外去T细胞单倍型骨髓联合外周血造血干细胞移植（haploidentical blood and marrow stem cell transplatation，HBMT）术后早期免疫重建与预后特征。方法以2010年1月至2012年12月在北京大学人民医院行HBMT的49例Ph阴性ALLCRl患者为研究对象，应用流式细胞术分别检测患者＋30d、＋60d及＋90d外周血CD19^＋、CD3^＋、CD4^＋、CD8^＋、CD4^＋CD45RO^＋、CD4^＋CD45RA^＋、CD4^＋CD28^＋及CD8^＋CD28^＋淋巴细胞亚群免疫重建指标，比较标危组（18例）、成人高危组（16例）及儿童高危组（15例）淋巴细胞亚群早期重建规律、生存状况及预后。结果三组患者CD3^＋、CD4^＋CD28^＋、CD8^＋CD28^＋、CD4^＋CD45RO^＋和CD4^＋CD45RA^＋等早期免疫重建（＋30d、＋60d及＋90d）指标差异均无统计学意义。标危组、成人高危组及儿童高危组患者2年复发率（27．8％、31．3％、26．7％，P=0．957）、2年非复发死亡率（11．1％、0、13．3％，P=0．185）、2年无白血病生存率（61．1％、68．8％、60．0％，P=0．834）及总生存率（77．8％、68．8％、60．0％，P=O．529）差异均无统计学意义。三组患者移植后100d内Ⅱ-Ⅳ度急性移植物抗宿主病发生率（44．4％、12．5％、46．7％，P=0．075）和2年总慢性移植物抗宿主病发生率（61．1％、50．O％、40．0％，P=0．249）差异无统计学意义。结论在HBMT模式下，Ph阴性ALLCRl高危组与标危组患者移植后可取得相当的早期免疫重建，这可能是克服移植前高危因素并取得相同移植疗效的免疫机制之一。

Objective To compare the early stage immune reconstitution of high- and standard- risk Philadelphia chromosome-negative acute lymphoblastic leukemia （ALL） CR1 patients who had haploidentical blood and marrow stem cell transplantation （HBMT）. Methods A total of 49 Ph-negative ALL CR1 patients who received HBMT and had complete early stage immune reconstitution data（＋30, ＋60 and ＋90 d post transplantation） from Jan. 2010 to Dec. 2012 were enrolled. Immunophenotyping for B and T lymphocytes was performed post HBMT via flow cytometry. Fresh peripheral blood cells were stained with fluorochrome-labeled monoclonal antibodies against cluster of differentiation CD19, CD3, CD4, CD8, CD45RO, CD45RA and CD28. The early reconstitution of lymphocyte subsets, survival and prognosis between standard-risk group, high-risk adult group and high-risk children group were compared. Results There were no significant differences in all these T lymphocyte subsets among three groups at the three check points （P〉0.05）. Moreover, at the same time, comparable outcome had been achieved between standard-risk group （n= 18 ）, high-risk adult group （n= 16） and high-risk children group （n= 15 ）. There were no differences in 2-y relapse incidence （27.8% vs 31.3% vs 26.7%, P=0.957）, 2-y non-relapse mortality （11.1% vs 0 vs 13.3%, P=0.185）, 2-y leukemia free survival （61.1% vs 68.8% vs 60.0%, P=0.834） and overall survival （77.8% vs 68.8% vs 60.0%, P=0.529） among the three groups. Incidence of grade Ⅱ-Ⅳ aGVHD was 44.4% vs 12.5% vs 46.7%（P=-0.075） and incidence of cGVHD was 61.1% vs 50.0% vs 40.0% （P=0.249）. Conclusion Comparison of immune reconstitution at early stage may be a reasonable cause to explain that equivalent outcomes were observed among high- and standard-risk Ph-negative ALL CR1 patients after HBMT.