A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

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% .

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, “41%, and 36%” for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Effects of hematological complete remission status before transplantation on outcomes of patients with B-cell acute lymphoblastic leukemia receiving haploidential stem cell transplantation / 临床检验杂志

Objective@#To investigate the association of hematological complete remssion (HCR) status on the outcomes of the patients with B-cell acute lymphoblastic leukemia (B-ALL) who were undergoing haploidentical stem cell transplantation (Haplo-SCT). @*Methods@#Retrospective analysis was performed on 317 patients with B-ALL who received Haplo-SCT with HCR before transplantation in the Institute of Hematology, Peking University from September 2012 to June 2016. A Cox proportional hazards model was used to analyze the effects of HCR status before transplantation on the outcomes of Haplo-SCT. @*Results@#The 3-year cumulative incidences of non-relapse mortality (NRM) and cumulative incidence of relapse (CIR) were 15% and 15%, respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 71% and 74%, respectively. There was no statistical difference for 3-year NRM, CIR and LFS among the HCR patients with recovery of absolute neutrophil count (ANC) and platelet (CR) group, without recovery of ANC and with or without recovery of platelet (CRi) group and those in HCR with recovery of ANC but without recovery of platelet (CRp) group (P value ＞0.05 for all). The probability of OS in cases of CR group was significantly higher than that of CRi group (76% vs 59%，P=0.049). Multivariate analysis showed that factors associated with CIR included pre-transplantation minimal residual disease (P=0.006) and chronic GVHD (P=0.020). Platelet engraftment was associated with NRM, LFS, and OS (P＜0.001 for all). Grades Ⅲ-Ⅳ GVHD was associated with NRM (P＜0.001) and OS (P=0.035). Chronic GVHD was correlated with LFS (P＜0.001). @*Conclusion@#Our results indicate that no effect of HCR status before transplant on the outcomes was observed in patients with B-ALL who underwent Haplo-SCT.