单倍型造血干细胞移植和HLA相合同胞供者造血干细胞移植治疗急性B淋巴细胞白血病的回顾性比较研究

OBJECTIVE: 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）. METHODS: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT（n＝788）or underwent MSDT（n＝210）were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry（MFC）. RESULTS: 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％CI 23.8％–29.4％）, respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1％（95％CI 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％CI 15.0％–19.7％）and 13.8％（95％CI 11.6％–16.0％）, respectively. The 3-year probabilities of leukemia-free survival（LFS）and overall survival（OS）were 69.1％（95％CI 66.1％–72.1％）and 73.0％（95％CI 70.2％–75.8％）, respectively. In the total patient group, cases with positive Pre-MRD（n＝282）experienced significantly higher CIR than that of subjects with negative Pre-MRD［n＝716, 31.6％（95％CI 25.8％–37.5％）vs 14.3％（95％CI 11.4％–17.2％）, P<0.001］. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT（n＝219）had a lower 3-year CIR than that of cases who underwent MSDT［n＝63, 27.2％（95％CI 21.0％–33.4％）vs 47.0％（95％CI 33.8％–60.2％）, P＝0.002］. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group（n＝716）, cases with Pre-MRD<0.01％ group（n＝46）, cases with Pre-MRD 0.01％–<0.1％ group（n＝117）, cases with Pre-MRD 0.1％–<1％ group（n＝87）, and cases with Pre-MRD≥1％ group（n＝32）. For subjects in the Pre-MRD<0.01％ group, haplo-HSCT（n＝40）had a lower CIR than that of MSDT［n＝6, 10.0％（95％CI 0.4％–19.6％）vs 32.3％（95％CI 0％–69.9％）, P＝0.017］. For patients in the Pre-MRD 0.01％–<0.1％ group, haplo-HSCT（n＝81）also had a lower 3-year CIR than that of MSDT［n＝36, 20.4％（95％CI 10.4％–30.4％）vs 47.0％（95％CI 29.2％–64.8％）, P＝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％（n＝163）was performed, the results showed that cases received haplo-HSCT（n＝121）experienced lower 3-year CIR［16.0％（95％CI 9.4％–22.7％）vs 40.5％（95％CI 25.2％–55.8％）, P<0.001］, better 3-year LFS［78.2％（95％CI 70.6％–85.8％）vs 47.6％（95％CI 32.2％–63.0％）, P<0.001］and OS［80.5％（95％CI 73.1％–87.9％）vs 54.6％（95％CI 39.2％–70.0％）, P<0.001］than those of MSDT（n＝42）, but comparable in 3-year NRM［5.8％（95％CI 1.6％–10.0％）vs 11.9％（95％CI 2.0％–21.8％）, P＝0.188］. Multivariate analysis showed that haplo-HSCT was associated with lower CIR（HR＝0.248, 95％CI 0.131–0.472, P<0.001）, and superior LFS（HR＝0.275, 95％CI 0.157–0.483, P<0.001）and OS（HR＝0.286, 95％CI 0.159–0.513, P<0.001）. CONCLUSION: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1％.