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.