Minimal residual disease as a predictive factor for relapse after allogeneic hematopoietic stem cell transplant in adult patients with acute myeloid leukemia in first and second complete remission

Rada M Grubovikj, Asif Alavi, Ahrin Koppel, Mary Territo, Gary J Schiller, Rada M Grubovikj, Asif Alavi, Ahrin Koppel, Mary Territo, Gary J Schiller

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is potentially curative for patients with high-risk leukemia, but disease recurrence remains the leading cause of treatment failure. Our objective was to determine the impact of minimal residual disease (MRD) by any technique in adult patients with acute myeloid leukemia (AML) in morphologic first and second complete remission undergoing allo-SCT. Fifty nine patients were eligible for the study of 160 patients transplanted over ten years. For the MRD assessment we used multiparametric flow cytometry, cytogenetics and fluorescent in situ hybridization; 19 patients (32.2%) were identified as MRD positive. Patients with MRD had a consistently worse outcome over those without MRD, with 3-years leukemia-free survival (LFS) of 15.8% vs. 62.4% and overall survival (OS) of 17.5% vs. 62.3%. Relapse rate was significantly higher in MRD-positive patients; 3 years relapse rate in MRD-positive patients was 57.9% vs. 15.1% in MRD-negative patients. Detection of MRD in complete remission was associated with increased overall mortality (HR = 3.3; 95% CI: 1.45-7.57; p = 0.0044) and relapse (HR = 5.26; 95% CI: 2.0-14.0; p = 0.001), even after controlling for other risk factors. Our study showed that for patients in morphologic complete remission the presence of MRD predicts for significantly increased risk of relapse and reduced LFS and OS.

Figures

Figure 1
Figure 1
Overall survival by CR and MRD.
Figure 2
Figure 2
Leukemia free survival by CR and MRD.
Figure 3
Figure 3
Relapse by CR and MRD.
Figure 4
Figure 4
Transplantation related mortality by CR and MRD.

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