Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis

Abstract

Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (hazard ratio=2.76 [1.90–4.00]), overall survival (hazard ratio=2.36 [1.73–3.22]), and cumulative incidence of relapse (hazard ratio=3.65 [2.53–5.27]), but not non-relapse mortality (hazard ratio=1.12 [0.81–1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I2=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation.

Acute leukemia in the time of COVID-19

“…Literature data on the impact of delayed transplant is ambiguous, obscured by differences in stem cell source and disease subtype. However, if a delay in transplant results in the reappearance of a significant minimal residual disease (MRD), a negative impact on survival is well established [9]. Furthermore, to ensure the possibility of the graft, EBMT strongly recommends securing stem cell product by freezing HSCs prior to conditioning, or to have a back-up donor [7].…”

<p>Strategies for minimal residual disease detection: current perspectives</p>

“…Many published data support the notion that the presence of MRD immediately prior to allo-HSCT is a strong, independent predictor of post-transplant outcomes in AML. 42 The MRD positivity has been defined as one of the stronger predictive factors both in the ablative and nonmyeloablative transplants. 43 In a large study carried out in 279 AML patients, Zhou et al investigated MRD before and after HSCT.…”

A novel predictive approach for GVHD after allogeneic SCT based on clinical variables and cytokine gene polymorphisms

“…This would be of special relevance in those patients with persistent minimal residual disease before transplantation. 49 Of course, before making any recommendations, these findings must be validated in prospective studies with large cohorts to demonstrate their clinical utility. …”