Post-transplant day +100 MRD detection rather than mixed chimerism predicts relapses after allo-SCT for intermediate risk AML patients transplanted in CR.

BACKGROUND

Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplant relapses in AML patients. Nevertheless, the predictive values of both approaches in homogeneous population remain underinvestigated. Here, we suggest that MRD may have a higher predictive value for relapses than mixed chimerism (MC) in intermediate risk AML patients.

PATIENTS AND METHODS

79 patients with intermediate risk AML (male, n=40, median age, 57 (19-77)) were included. MRD detection on day +100 was performed in bone marrow (multiparameter flow cytometry and quantitative real-time PCR for NPM1-mutated patients). Chimerism analysis was measured in peripheral blood. MC was defined as persistence of <99.9% of donor alleles.

RESULTS

The area under the ROC curve was highest for qPCR-MRD (0.93) followed by MFC-MRD (0.80) and MC (0.65). The highest relapses at 3 years were observed in day +100 qPCR-MRD positive patients (100%) followed by MFC-MRD positive patients (55%, p<0.001). No patients with MC and without detectable MRD developed relapses. The 3-year OS and LFS for patients with MC without detectable MRD were both 86% (61-96%) compared with day +100 MFC-MRD positive (OS: 61%, 36-84%; LFS: 30%, 11-59%) and with day +100 qPCR-MRD positive patients (OS: 17%, 3-56%, p=0.001; LFS: 0%, p<0.001).

CONCLUSIONS

In intermediate-risk AML, the qPCR-MRD on day +100 is highly predictive for relapse and long-term survival after allo-SCT, closely followed by MFC-MRD. In contrast, the chimerism status has limited predictive potential. Thus, molecular and flow-cytometric MRD monitoring in the first months post-transplant rather than MC is able to identify patients with an increased relapse risk who may benefit from early post-transplant pre-emptive intervention.