Abstract
BackgroundThis study compared the effects of pre-transplantation minimal residual disease (pre-MRD) on outcomes in AML patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical allografts.MethodsA retrospective study (n = 339) and a prospective study (n = 340) were performed. MRD was determined using multiparameter flow cytometry.ResultsEither after retrospective or prospective analysis, patients with negative pre-MRD (pre-MRDneg) had a lower incidence of relapse than those with positive pre-MRD (pre-MRDpos) in MSDT settings (P < 0.001 for all), but relapse was comparable in Haplo-SCT settings for patients with pre-MRDneg versus pre-MRDpos (P = 0.866 and 0.161, respectively). In either the retrospective (n = 65) or the prospective study (n = 76), pre-MRDpos subjects receiving Haplo-SCT experienced a lower incidence of relapse than those who underwent MSDT (P < 0.001 and p = 0.017, respectively). Of the patients with pre-MRDpos in either the total (n = 141) or the subgroup excluding cases which received donor lymphocyte infusion (DLI; n = 105), those who underwent MSDT had a higher incidence of relapse than those receiving haplo-SCT (P < 0.01 for all). Multivariate analysis showed that, for pre-MRDpos cases, haplo-SCT was associated with a low incidence of relapse and with better LFS and OS in either retrospective group, prospective group, combination groups, or subgroup not including cases which received DLI.ConclusionsThe results indicated that, for pre-MRD-positive AML patients, haplo-SCT was associated with lower incidence of relapse and better survival, suggesting a stronger anti-leukemia effect.
Highlights
This study compared the effects of pre-transplantation minimal residual disease on outcomes in acute myeloid leukemia (AML) patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical allografts
The results indicated that, for pre-minimal residual disease (MRD)-positive AML patients, haplo-stem cell transplantation (SCT) was associated with lower incidence of relapse and better survival, suggesting a stronger anti-leukemia effect
Increasing evidence suggests that the presence of minimal residual disease (MRD) before and after transplantation, which is detectable by multiparameter flow cytometry (MFC), identifies a subgroup of patients that is at high risk of relapse [12,13,14,15,16,17,18]
Summary
This study compared the effects of pre-transplantation minimal residual disease (pre-MRD) on outcomes in AML patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical allografts. Over the last 10 years, T-cell-replete haploidentical SCT (haplo-SCT), especially unmanipulated haplo-SCT with anti-thymocyte globulin (ATG) [3, 9, 10] or with postcyclophosphamide (PT/Cy) [3], is widely accepted as a viable alternative for patients without HLA-identical donors, and its outcomes may be comparable to those of HLA-identical sibling donor transplantation (MSDT) or unrelated donor transplantation (MUDT) [4, 9]. It remains unclear whether haplo-SCT have different antileukemia effects than other allografts [11]. Studies have focused mainly on the association of flow-cytometry-detected MRD with the outcomes of AML patients who underwent HLA-matched sibling donor transplantation (MSDT), cord blood transplantation (CBT), and MUDT [14, 15, 19, 20]
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