Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia

Abstract

disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML), determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial end points.OBJECTIVE To examine the association between MRD status and disease-free survival (DFS) and overall survival (OS) in patients with AML using scientific literature.

Measurable residual disease in pediatric acute myeloid leukemia: a systematic review

“…The heterogeneity in technique, timepoint of assessment, the definition of MRD positivity, and in outcome parameters in pediatric AML impacted our review and made a meta-analysis next to impossible. The recent systematic review and meta-analysis about MRD in AML by Short et al compared eighty-one publications without distinguishing pediatric and adult populations and included nine of the thirteen pediatric AML articles described in this review [28]. Although this review confirms our finding that MRD negativity is associated with better survival outcome, differences in included studies limit the comparability [28].…”

Is there an impact of measurable residual disease as assessed by multiparameter flow cytometry on survival of AML patients treated in clinical practice? A population-based study

“…A recent meta-analysis indicates that MRD-negativity is associated with superior survival [15]. The studies included in the meta-analysis did not prospectively adjust consolidation therapy based on MRD-status [15]. We hypothesize that the lack of observed association between MRD and OS in our study is both related to patient and leukemia characteristics, and to the implementation of MRD-information during the planning of subsequent treatment, which was generally based on the national guidelines.…”

“…Measurable residual disease has the potential to provide information about the risk of relapse and death in AML [2,3,14,15]. However, it remains unclear how MRD should be analyzed and interpreted in order to guide therapeutic decisions [3].…”

“…A recent meta-analysis indicates that MRD-negativity is associated with superior survival [15]. The studies included in the meta-analysis did not prospectively adjust consolidation therapy based on MRD-status [15].…”

Azacitidine maintenance after allogeneic hematopoietic cell transplantation for MDS and AML

“…The eligibility criterion requirement to be in complete remission after transplant, with enrollment possible 40 to 100 days post-alloHCT, contributed to the .75% screen failure rate of that study (.748 patients screened; reasons for 520 of the 561 recorded screen failures are listed in Table 1 of the study by Oran et al). 9 Compared with the 87 patients who received azacitidine post-alloHCT as part of that study, another 62 of the screened patients did so outside that clinical trial, including 26 for the indication of "minimal" (ie, measurable) residual disease (MRD), [10][11][12] representing a clear source of potential bias. Although oral azacitidine (CC-486) improved survival for MRD-positive and MRD-negative patients in a nontransplant maintenance setting, 13 information on all of the MRD testing performed in this post-alloHCT study would have been important, particularly because MRD results available to the treating physicians may have influenced decisions regarding participation on this trial.…”