Minimal residual disease monitoring after allogeneic transplantation may help to individualize post‐transplant therapeutic strategies in acute myeloid malignancies

Abstract

This study evaluates the prognostic value of minimal residual disease (MRD) monitoring by multiparametric flow cytometry in 41 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing allogeneic transplantation. MRD assessment after transplant (day +100) allowed to discriminate different risk populations, being the most significant cut‐off value for outcome level of MRD </≥10−3. Outcome was significantly better among patients with low (<10−3) versus high (≥10−3) MRD at day +100 after transplant. Thus, overall survival was 73% versus 25% at 4 years among patients with low versus high MRD at day +100 after transplant (P = 0.002); 74% of patients with low MRD were event free at 4 years as compared to 17% among patients with high MRD (P = 0.01). In multivariate analysis, MRD value as well as chronic GVHD significantly influenced outcome. In conclusion, MRD monitoring early post‐transplant is an important tool for outcome prediction and should be considered in decision making after allogeneic transplantation. Am. J. Hematol. 2009. © 2008 Wiley‐Liss, Inc.

Pre-transplant MRD predicts outcome following reduced-intensity and myeloablative allogeneic hemopoietic SCT in AML

“…In accordance with Diez-Campelo et al, 23 our data suggest a worse prognosis for patients who are MRD-positive by MFC at 3 months post-transplant, compared with those who are MRD-negative. With only 10 patients demonstrating residual disease at this time point in our study, these results warrant confirmation, and additional evaluation is required to determine the prognostic potential of MRD monitoring at other time points post-HSCT.…”

“…There remains a need for standardization of MFC techniques and to establish the level at which MRD becomes clinically relevant. 8,10,11,13,20,23,24,27 As expected, we identified a difference in clinical characteristics between patients who are MRD-positive and -negative pre-HSCT; 80% of patients with secondary AML remained MRD-positive and patients in the MRD-positive group were more likely to have failed induction therapy. MRD-positive patients were more heavily treated pre-transplant, having received a salvage regimen in 36/41 cases, suggesting that this group had a higher risk to develop disease than the MRD-negative cohort.…”

“…Smaller studies have suggested an association between the presence of MRD post-HSCT and relapse, 23,24 but currently there is insufficient evidence to suggest modification of post transplant management on the basis of post transplant MRD status.…”

Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: Current Status

“…Further, we and others have shown that flow cytometric immunophenotypic aberrancies of MDS marrow cells pre-HCT impact post-HCT relapse (Diez-Campelo et al 2009;Scott et al 2008;Stetler-Stevenson et al 2001;Wells et al 2003). Even among patients with less than 5% marrow myeloblasts, those with an aberrant phenotype had a significantly higher relapse probability (Scott et al 2008).…”

“…Multiparameter flow cytometry has been used effectively to show that aberrancy of marrow blasts pre-HCT significantly influenced outcome after HCT (Diez-Campelo et al 2009;Scott et al 2008;Wells et al 2003). However, since most patients with MDS have aberrant marrow cell phenotypes by flow cytometry and may not be in remission as classically defined for patients with AML, the definition of minimal residual disease in patients with MDS is a matter of debate and requires further work.…”