Clinical relevance of an objective flow cytometry approach based on limit of detection and limit of quantification for measurable residual disease assessment in acute myeloid leukemia. A post-hoc analysis of the GIMEMA AML1310 trial
Francesco Buccisano,
Raffaele Palmieri,
Alfonso Piciocchi,
Valentina Arena,
Luca Maurillo,
Maria-Ilaria Del Principe,
Giovangiacinto Paterno,
Maria-Antonietta Irno-Consalvo,
Tiziana Ottone,
Mariadomenica Divona,
Consuelo Conti,
Daniela Fraboni,
Serena Lavorgna,
William Arcese,
Maria Teresa Voso,
Adriano Venditti
Affiliations
Francesco Buccisano
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Raffaele Palmieri
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Alfonso Piciocchi
Centro Dati Fondazione GIMEMA Onlus, Roma
Valentina Arena
Centro Dati Fondazione GIMEMA Onlus, Roma
Luca Maurillo
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Maria-Ilaria Del Principe
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Giovangiacinto Paterno
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Maria-Antonietta Irno-Consalvo
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Tiziana Ottone
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Mariadomenica Divona
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Consuelo Conti
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Daniela Fraboni
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Serena Lavorgna
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
William Arcese
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”, Roma; Rome Transplant Network, Roma
Maria Teresa Voso
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Adriano Venditti
Ematologia, Dipartimento di Biomedicina e Prevenzione, Universita di Roma “Tor Vergata”
Using a multiparametric flow cytometry assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients with acute myeloid leukemia. This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined measurable residual disease (MRD) threshold of 0.035% bone marrow residual leukemic cells (RLC) calculated on mononuclear cells, 154 (59%) of the 261 patients were negative (MRD <0.035%) and 107 (41%) were positive (MRD ≥0.035%). Using LOD and LOQ, we selected the following categories of patients: (i) LODneg if RLC were below the LOD (74; 28.4%); (ii) LODpos-LOQneg if RLC were between the LOD and LOQ (43; 16.5%); and (iii) LOQpos if RLC were above the LOQ (144; 54.4%). Two-year overall survival of these three categories of patients was 75.4%, 79.8% and 66.4%, respectively (P=0.1197). Given their superimposable outcomes, the LODneg and LODpos-LOQneg categories were combined. Two-year overall survival of LODneg/LODpos-LOQneg patients was 77.0% versus 66.4% of LOQpos individuals (P=0.043). This figure was challenged in univariate analysis (P=0.046, hazard ratio=1.6, 95% confidence interval: 1.01-2.54) which confirmed the independent role of the LOD-LOQ approach in determining overall survival. In the AML1310 protocol, using the threshold of 0.035%, 2-year overall survival of patients with MRD <0.035% and MRD ≥0.035% was 74.5% versus 66.4%, respectively (P=0.3521). In conclusion, the use of the LOD-LOQ method results in more sensitive detection of MRD that, in turn, translates into a more accurate recognition of patients with different outcomes.