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Monitoring of minimal residual disease in adult acute myeloid leukemia using peripheral blood as an alternative source to bone marrow

All authors from the Dept. of Hematology, Policlinico Tor Vergata and Ospedale S.Eugenio, Rome, Italy

Correspondence: Adriano Venditti, MD, Cattedra di Ematologia, Università Tor Vergata, viale Oxford 81, 001133 Rome, Italy. E-mail: adriano.venditti{at}uniroma2.it

Background and Objectives: To date, bone marrow (BM) is the most common source of cells to use in order to assess minimal residual disease (MRD) in acute myeloid leukemia (AML). In the present study, we investigated whether peripheral blood (PB) could be an alternative source of cells for monitoring MRD in AML.

Design and Methods: Fifty patients with AML were monitored for MRD after the achievement of complete remission. Using multiparametric flow cytometry we compared the levels of MRD in 50 and 48 pairs of BM and PB after induction and consolidation, respectively.

Results: After induction and consolidation therapy, the findings in BM and PB were significantly concordant (r=0.86 and 0.82, respectively, p<0.001 for both comparisons). The cut-off value of residual leukemic cells in PB which correlated with outcome was 1.5x10^–4. Thirty-three of 43 (77%) patients with >1.5x10^–4 residual leukemic cells in PB after induction had a relapse, whereas the seven patients with lower levels did not (p=0.0002). After consolidation, 38 patients had a level of MRD >1.5x10^–4 and 31 (82%) had a relapse; nine out of the remaining ten patients, whose levels of MRD were below 1.5x10^–4, are still relapse-free (p=0.00006). In multivariate analysis, PB MRD status at the end of consolidation was found to have a significant effect on relapse-free survival (p=0.036).

Interpretation and Conclusions: These preliminary results indicate that: (i) PB evaluation can integrate BM assessment for MRD detection in patients with AML; (ii) PB MRD status at the end of consolidation therapy may provide useful prognostic information.

Key words: AML, MRD, multiparametric flow-cytometry, leukemia associated phenotype, peripheral blood.