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.
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.
Lane
Steven
S
Department of Haematology, Queensland Health Pathology Service, University of Queensland, Brisbane, QLD, Australia.
Saal
Russell
R
Mollee
Peter
P
Jones
Mark
M
Grigg
Andrew
A
Taylor
Kerry
K
Seymour
John
J
Kennedy
Glen
G
Williams
Bronwyn
B
Grimmett
Karen
K
Griffiths
Vanessa
V
Gill
Devinder
D
Hourigan
Matthew
M
Marlton
Paula
P
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
D050660:Core Binding Factors; D012333:RNA, Messenger