Impact of pre-transplantation minimal residual disease determined by multiparameter flow cytometry on the outcome of AML patients with FLT3-ITD after allogeneic stem cell transplantation
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In this study, using multiparameter flow cytometry (FCM), we investigate the impact of minimal residual disease prior to transplantation (pre-MRD) on the transplant outcomes of AML patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation. A total of 20 patients who received HLA-matched sibling donor transplantation (MSDT) and 63 patients who received unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) were enrolled. Patients were classified into four groups based on the status of pre-FCM: group 1 with positive pre-FCM before MSDT, group 2 with negative pre-FCM before MSDT, group 3 with positive pre-FCM before haplo-HSCT, and group 4 with positive pre-FCM before haplo-HSCT. The results showed that patients in group 1 had the highest cumulative incidence of relapse (2-year CIR, 75.0%), the lowest leukemia-free survival (2-year LFS, 33.3%), and the overall survival (2-year OS, 25.0%) among all four groups. The other three groups of patients had comparable CIR (2-year CIR: group 2 vs. 3 vs. 4, 12.5% vs. 31.3% vs. 22.2%, P > 0.05) and LFS (2-year LFS: group 2 vs. 3 vs. 4, 87.5% vs. 62.5% vs. 66.5%, P > 0.05). Multivariate analysis indicated that disease status (> CR) and pre-MRD were associated with a higher CIR and a lower LFS when patients were classified by pre-MRD and transplant type. Our results suggested that AML patients with FLT3-ITD were able to be separated into high-risk and low-risk relapse groups based on pre-MRD, as determined by multiparameter FCM. Haplo-HSCT might overcome the negative impact of pre-MRD on patient outcomes compared to MSDT. These results require further investigation in prospective study with large numbers of cases.
KeywordsAcute myeloid leukemia Allogeneic hematopoietic stem cell transplantation Minimal residual disease Multiparameter flow cytometry FLT3-ITD
We thank all of the faculty members who participated in these studies. We would also like to thank American Journal Experts (https://www.aje.cn/) for assistance in editing this manuscript.
Contribution: Y.-J.C. designed the study; X.-S. Z., Z.-D.W., and Y.-J.C. collected, analyzed the data, and drafted the manuscript; all authors contributed to data interpretation, manuscript preparation, and approval of the final version.
This work was supported (in part) by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 81621001), the National Natural Science Foundation of China (Grant No. 81670175), the Scientific Research Foundation for Capital Medicine Development (2016-1-4082), and the Beijing Key Laboratory for Hematopoietic Stem Cell Transplantation.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
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