title: Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients.
abstract: Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB-WT1 ≥ 16/10(4) ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q-PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk-adapted, postinduction therapy of AML.
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Skert
authors.affiliation: Division of Hematology, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Borlenghi
authors.affiliation: Centro di Ricerca Emato-oncologica AIL (CREA) Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chiarini
authors.affiliation: Division of Hematology, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cattaneo
authors.affiliation: Division of Hematology, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Morello
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cancelli
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cattina
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cerqui
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pagani
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Passi
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Ribolla
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.|Centro di Ricerca Emato-oncologica AIL (CREA) Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bernardi
authors.affiliation: Centro di Ricerca Emato-oncologica AIL (CREA) Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Giustini
authors.affiliation: Division of Hematology, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lamorgese
authors.affiliation: Laboratorio Analisi, Department of Molecular and Translational Medicin, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Ruggeri
authors.affiliation: Centro di Ricerca Emato-oncologica AIL (CREA) Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Imberti
authors.affiliation: Centro di Ricerca Emato-oncologica AIL (CREA) Brescia, AO Spedali Civili di Brescia, Brescia, Italy.|Laboratorio Analisi, Department of Molecular and Translational Medicin, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.affiliation: Unit of Blood Disease and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.affiliation: Division of Hematology, AO Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics*; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D025721:WT1 Proteins
keywords: LAIP; WT1; minimal residual disease