title: A >or=1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor acute myeloid leukemia and predicts subsequent morphologic relapse.
abstract: Core binding factor acute myeloid leukemia (CBF AML), with t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) and the associated fusion gene transcripts AML1/ETO or CBFbeta/MYH11, has a favourable clinical prognosis although significant numbers of patients still suffer relapse. We examined the prognostic utility of serial bone marrow minimal residual disease (MRD) monitoring by RQ-PCR in a cohort of patients with CBF AML with long term clinical follow-up. Twenty-nine patients were evaluated with a median follow of 34 months. Twelve relapses occurred at a median of 11 months (range 4 - 17) from diagnosis. RQ-PCR levels at diagnosis, post-induction chemotherapy and post-consolidation were not predictive of outcome. However, a >or=1 log(10) rise at any stage in transcript level relative to the level from a remission bone marrow sample correlated with inferior leukemia free survival (LFS) and imminent morphologic relapse (hazard ratio 8.6). Relapses occurred a median of 60 days (range 45 - 272) after a log(10) rise. A >or=1 log(10) rise in transcript levels strongly predicts subsequent morphologic relapse in CBF AML and therefore defines molecular relapse. Our data support a simple RQ-PCR model for prediction of impending relapse which has the potential for widespread clinical applicability. Prospective identification of high risk patients will enable clinical trials to assess the efficacy of treatment initiated at molecular relapse.
authors.affiliation: Department of Haematology, Queensland Health Pathology Service, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Lane
authors.forename: Russell
authors.initials: R
authors.lastname: Saal
authors.forename: Peter
authors.initials: P
authors.lastname: Mollee
authors.forename: Mark
authors.initials: M
authors.lastname: Jones
authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg
authors.forename: Kerry
authors.initials: K
authors.lastname: Taylor
authors.forename: John
authors.initials: J
authors.lastname: Seymour
authors.forename: Glen
authors.initials: G
authors.lastname: Kennedy
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Williams
authors.forename: Karen
authors.initials: K
authors.lastname: Grimmett
authors.forename: Vanessa
authors.initials: V
authors.lastname: Griffiths
authors.forename: Devinder
authors.initials: D
authors.lastname: Gill
authors.forename: Matthew
authors.initials: M
authors.lastname: Hourigan
authors.forename: Paula
authors.initials: P
authors.lastname: Marlton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001856:Bone Marrow Examination; D002648:Child; D015331:Cohort Studies; D050660:Core Binding Factors; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012008:Recurrence
chemical_list: D050660:Core Binding Factors; D012333:RNA, Messenger