The significance of peri-transplantation minimal residual disease assessed by multiparameter flow cytometry on outcomes for adult AML patients receiving haploidentical allografts

Abstract

A retrospective study (n = 460) was performed to assess the relationship between minimal residual disease (MRD) and transplant outcomes in a haplo-stem cell transplantation (SCT) setting. Patients from the pre-MRDneg group and the pre-MRDpos group had comparable outcomes. Compared to post-MRDneg patients, post-MRDpos patients had a higher incidence of relapse (100.0% vs. 8.3%, p < 0.001), lower incidences of overall survival (OS) (16.9% vs. 78.2%, p < 0.001) and leukemia-free survival (LFS) (0% vs. 76.5%, p < 0.001), and comparable probability of NRM (13.4% vs. 16.9%, p = 0.560). In a second set of analyses, all adult AML patients undergoing haplo-SCT were classified into the MRD/MRD group, the MRD decreasing group, and the MRD increasing group according to MRD dynamics by flow cytometry peri-SCT. Compared to the other two groups, patients from the MRD increasing group had higher cumulative incidences of relapse (MRD increasing, 100.0%; MRD/MRD, 9.6%; MRD decreasing, 19.2%; p < 0.001) and worse probabilities of OS (MRD increasing, 28.5%; MRD/MRD, 76.3%; MRD decreasing, 76.0%; p < 0.001) and LFS (MRD increasing, 0.0%; MRD/MRD, 73.9%; MRD decreasing, 74.0%; p < 0.001). The results indicated that haploidentical allografts might have a beneficial anti-leukemia effect in eradicating pretransplantation MRD, and MRD assessment peri-SCT is useful for risk stratification from a practical perspective.

The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

“…Meanwhile, patients with a positive MRD status before HSCT may not benefit from haploidentical transplantation or myeloablative conditioning regimen. However, Liu et al did not observe an association between the pretransplantation MRD status and the outcomes of patients with AML receiving haploidentical transplants . This discrepancy may be mainly due to the limited number of patients in the current analysis.…”

“…Multigene next-generation sequencing (NGS) is another potential molecular method for MRD detection that is applicable for most patients with AML. However, the consensus list of genes 23 This discrepancy may be mainly due to the limited number of patients in the current analysis. Furthermore, a routine prophylactic donor lymphocyte infusion was administered to patients with refractory disease or in the second remission in that study, which may be another explanation for the discrepancy.…”

Cytogenetic risk score maintains its prognostic significance in AML patients with detectable measurable residual disease undergoing transplantation in remission: On behalf of the acute leukemia working party of the European society for blood and marrow transplantation

“…And, the data complement a recent ALWP/EBMT analysis suggesting superior outcomes for MRD positive patients younger than 50 years of age, with a myeloablative conditioning approach 9 . Alternatively, one may consider that the therapeutic intervention for MRD positive patients should not be in the form of additional therapy, but rather in guided donor selection as suggested by publications demonstrating that choice of alternative donors, namely umbilical cord grafts 30 or haploidentical donors 31,32 may improve on historical results with traditional donors.…”

Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia

“…Considering MRD was detected at different time points, several studies focused on the dynamic MRD change in predicting CIR for patients with acute leukemia [12,16,20,25,37,38] . For 279 patients with AML receiving allografts, pre-HSCT MRD and post-HSCT MRD were determined by MFC.…”