Monitoring of Minimal Residual Disease (MRD) in Acute Myeloid Leukemia Using Peripheral Blood (PB) as an Alternative Source to Bone Marrow (BM).

In acute myeloid leukemia (AML), the level of MRD as determined by multiparametric flow cytometry (MPFC) has been shown to impact on remission duration and survival. BM is the most common source to perform MRD assessment. We have previously showed that BM MRD negativity after consolidation was associated with a significantly longer relapse free survival (RFS) and overall survival (OS). However, in children with T acute lymphoid leukemia, it has been reported that PB might be used as an alternative source to BM for MRD studies. Based on this, we investigated whether PB might substitute for BM to monitor MRD in adult AML patients, showing the same prognostic value. Forty adult patients with AML were enrolled into the EORTC/GIMEMA protocols AML10/AML12 (age 61 yrs), all consisting in intensive induction and consolidation cycles, and, for patients aged −3 (range 1x10 −4 –1.64x10 −1 ) and 4.7x10 −3 (range, 3x10 −5 –9.3x10 −2 ), respectively (r=0.84, P −3 (range 2x10 −5 –6.3x10 −2 ) and 7.7x10 −3 (range 3.5x10 −5 –1.34x10 −1 ), respectively (r=0.82, P −4 ; in fact, 27 of 37 (73%) patients with PBRLC >1x10 −4 after induction had a relapse whereas, the 3 patients with −4 PBRLC did not (P=0.028). After consolidation, using the same threshold, 32 patients were considered MRD positive (MRDCons + ) and 81% (26) of them experienced a relapse; the remaining 6 patients, who were MRD negative (MRDCons − ) are still in complete remission (P=0.00033). Duration of RFS was significantly longer in the MRDCons − group (median not reached, range 1.7–71 months) as compared to the MRDCons + one (median 8.8 months, range 1–22) (P=0.005); in multivariate analysis, PB MRD status at the end of consolidation was an independent factor impacting on RFS (P=0.009). In conclusion: 1) PB may be used to monitor MRD in patients with AML, allowing closer monitoring of leukemia while sparing patients the discomfort of BM aspiration; 2) the level of MRD in the PB after consolidation therapy, may provide useful prognostic informations. Our results warrant further studies in a larger group of patients recruited to different treatment protocols and monitored at different time-points.