title: Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state.
abstract: The inv(16) cytogenetic subtype of acute myeloid leukemia (AML) has a relatively good prognosis. Many patients achieve complete remission (CR). The prognostic uncertainty of negative qualitative reverse transcription-polymerase chain reaction (RT-PCR) assays suggests the need to identify prognostically significant critical thresholds by real-time RT-PCR. A reliable and sensitive (10(-5)) real-time RT-PCR assay was set up for the evaluation of relevant CBFbeta-MYH11/ABL transcript ratios and was applied to the 21 patients with inv(16) AML routinely referred for cytogenetic and molecular monitoring in Seràgnoli Institute (Bologna, Italy) since 1990. Among the 18 patients who underwent ablative chemotherapy, all achieved CR with a 3-year disease-free survival probability of 63% (95% CI, 40%-87%) and no recorded events after 26 months. Five patients had relapses; 2 died of disease and 3 entered second CR. Analysis of the 125 bone marrow (or peripheral blood) samples studied by real-time RT-PCR showed that transcript ratios of samples taken during CR at any time before a relapse were always greater than 0.12%, whereas those of samples taken during first or second CR from patients who did not subsequently have relapses were always less than 0.25%. This suggests that transcript ratios greater than 0.25% may correspond to high risk for relapse, whereas ratios below 0.12% might indicate the patient is in a curable state. If confirmed, such thresholds could open the way to a new phase in post-CR therapeutic decision making for patients with inv(16) AML.
authors.affiliation: Institute of Hematology and Medical Oncology L. e A. Seràgnoli, University of Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Buonamici
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ottaviani
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Visani
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonifazi
authors.forename: Marilina
authors.initials: M
authors.lastname: Amabile
authors.forename: Carolina
authors.initials: C
authors.lastname: Terragna
authors.forename: Deborah
authors.initials: D
authors.lastname: Ruggeri
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Alessandro
authors.initials: A
authors.lastname: Isidori
authors.forename: Michele
authors.initials: M
authors.lastname: Malagola
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000235:genetics; D001856:Bone Marrow Examination; D016026:Bone Marrow Transplantation; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000648:ultrastructure*; D003131:Combined Modality Therapy; D003199:Computer Systems; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016313:Genes, abl; D006801:Humans; D007621:Karyotyping; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000097:blood / Q000235:genetics; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D016879:Salvage Therapy; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion