Wang Z D, Sun Y Q, Yan C H, Wang F R, Mo X D, Lyu M, Zhao X S, Han W, Chen H, Chen Y Y, Wang Y, Xu L P, Wang Y Z, Liu Y R, Cheng Y F, Zhang X H, Liu K Y, Huang X J, Chang Y J
Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
Zhonghua Xue Ye Xue Za Zhi. 2022 Mar 14;43(3):221-228. doi: 10.3760/cma.j.issn.0253-2727.2022.03.007.
To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (=788) or underwent MSDT (=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% 15.0% -19.7% ) and 13.8% (95% 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% 66.1% -72.1% ) and 73.0% (95% 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [=716, 31.6% (95% 25.8% -37.5% ) 14.3% (95% 11.4% -17.2% ) , <0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (=219) had a lower 3-year CIR than that of cases who underwent MSDT [=63, 27.2% (95% 21.0% -33.4% ) 47.0% (95% 33.8% -60.2% ) , =0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (=716) , cases with Pre-MRD<0.01% group (=46) , cases with Pre-MRD 0.01% -<0.1% group (=117) , cases with Pre-MRD 0.1% -<1% group (=87) , and cases with Pre-MRD≥1% group (=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (=40) had a lower CIR than that of MSDT [=6, 10.0% (95% 0.4% -19.6% ) 32.3% (95% 0% -69.9% ) , =0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (=81) also had a lower 3-year CIR than that of MSDT [=36, 20.4% (95% 10.4% -30.4% ) 47.0% (95% 29.2% -64.8% ) , =0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (=163) was performed, the results showed that cases received haplo-HSCT (=121) experienced lower 3-year CIR [16.0% (95% 9.4% -22.7% ) 40.5% (95% 25.2% -55.8% ) , <0.001], better 3-year LFS [78.2% (95% 70.6% -85.8% ) 47.6% (95% 32.2% -63.0% ) , <0.001] and OS [80.5% (95% 73.1% -87.9% ) 54.6% (95% 39.2% -70.0% ) , <0.001] than those of MSDT (=42) , but comparable in 3-year NRM [5.8% (95% 1.6% -10.0% ) 11.9% (95% 2.0% -21.8% ) , =0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (=0.248, 95% 0.131-0.472, <0.001) , and superior LFS (=0.275, 95% 0.157-0.483, <0.001) and OS (=0.286, 95% 0.159-0.513, <0.001) . Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .
为了研究单倍型造血干细胞移植（haplo-HSCT）与人类白细胞抗原（HLA）相匹配的同胞供体移植（MSDT）相比，在治疗移植前微小残留病（Pre-MRD）阳性的急性B淋巴细胞白血病（B-ALL）中是否有效。对998例在造血干细胞移植前处于完全缓解期的B-ALL患者进行了回顾性分析，这些患者要么接受了单倍型造血干细胞移植（n = 788），要么接受了同胞供体移植（n = 210）。根据采用多参数流式细胞术（MFC）测定的Pre-MRD评估移植前白血病负担。在这些患者中，997例（99.9%）实现了持续、完全的供体嵌合。中性粒细胞植入、血小板植入以及Ⅱ-Ⅳ级急性移植物抗宿主病（GVHD）的100天累积发生率分别为99.9%（997/998）、95.3%（951/998）和26.6%（95% CI 23.8% - 29.4%）。慢性GVHD的3年累积发生率为49.1%（95% CI 45.7% - 52.4%）。998例患者的3年复发累积发生率（CIR）和非复发死亡率（NRM）分别为17.3%（95% CI 15.0% - 19.7%）和13.8%（95% CI 11.6% - 16.0%）。3年无白血病生存率（LFS）和总生存率（OS）分别为69.1%（95% CI 66.1% - 72.1%）和73.0%（95% CI 70.2% - 75.8%）。在整个患者组中，Pre-MRD阳性（n = 282）的病例的CIR显著高于Pre-MRD阴性的病例[= 716，31.6%（95% CI 25.8% - 37.5%）对14.3%（95% CI 11.4% - 17.2%），P < 0.001]。对于Pre-MRD阳性亚组中的患者，接受单倍型造血干细胞移植（n = 219）的病例的3年CIR低于接受同胞供体移植的病例[= 63，27.2%（95% CI 21.0% - 33.4%）对47.0%（95% CI 33.8% - 60.2%），P = 0.002]。998例患者共分为五个亚组，包括Pre-MRD阴性组（n = 716）、Pre-MRD < 0.01%组（n = 46）、Pre-MRD 0.01% - < 0.1%组（n = 117）、Pre-MRD 0.1% - < 1%组（n = 87）和Pre-MRD≥1%组（n = 32）。对于Pre-MRD < 0.01%组的患者，单倍型造血干细胞移植（n = 40）的CIR低于同胞供体移植[= 6，10.0%（95% CI 0.4% - 19.6%）对32.3%（95% CI 0% - 69.9%），P = 0.017]。对于Pre-MRD 0.01% - < 0.1%组的患者，单倍型造血干细胞移植（n = 81）的3年CIR也低于同胞供体移植[= 36，20.4%（95% CI 10.4% - 30.4%）对47.0%（95% CI 29.2% - 64.8%），P = 0.004]。在其他三个亚组中，接受单倍型造血干细胞移植的患者与接受同胞供体移植的患者的3年CIR相当。对Pre-MRD < 0.1%（n = 163）的患者进行亚组分析，结果显示接受单倍型造血干细胞移植（n = 121）的病例的3年CIR较低[16.0%（95% CI 9.4% - 22.7%）对40.5%（95% CI 25.2% - 55.8%），P < 0.001]，3年LFS较好[78.2%（95% CI 70.6% - 85.8%）对47.6%（95% CI 32.2% - 63.0%），P < 0.001]，OS较好[80.5%（95% CI 73.1% - 87.9%）对54.6%（95% CI 39.2% - 70.0%），P < 0.001]，但3年NRM相当[5.8%（95% CI 1.6% - 10.0%）对11.9%（95% CI 2.0% - 21.8%），P = 0.188]。多因素分析显示，单倍型造血干细胞移植与较低的CIR相关（P = 0.248，95% CI 0.131 - 0.472，P < 0.001），以及较好的LFS（P = 0.275，95% CI 0.157 - 0.483，P < 0.001）和OS（P = 0.286，95% CI 0.159 - 0.513，P < 0.001）。在治疗Pre-MRD < 0.1%的B-ALL患者中，单倍型造血干细胞移植比同胞供体移植具有生存优势。
Zotero 插件