A 1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor accute myeloid leukemia and predicts subsequent morphologic relapse

Lane, Steven, Saal, Russell, Mollee, Peter, Jones, Mark, Grigg, Andrew, Taylor, Kerry, Seymour, John, Kennedy, Glen, Williams, Bronwyn, Grimmett, Karen, Griffiths, Vanessa, Gill, Devinder, Hourigan, Matthew and Marlton, Paula (2008) A 1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor accute myeloid leukemia and predicts subsequent morphologic relapse. Leukemia & Lymphoma, 49 3: 517-523. doi:10.1080/10428190701817266


Author Lane, Steven
Saal, Russell
Mollee, Peter
Jones, Mark
Grigg, Andrew
Taylor, Kerry
Seymour, John
Kennedy, Glen
Williams, Bronwyn
Grimmett, Karen
Griffiths, Vanessa
Gill, Devinder
Hourigan, Matthew
Marlton, Paula
Title A 1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor accute myeloid leukemia and predicts subsequent morphologic relapse
Formatted title
A > 1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor accute myeloid leukemia and predicts subsequent morphologic relapse
Journal name Leukemia & Lymphoma   Check publisher's open access policy
ISSN 1029-2403
Publication date 2008-01-31
Year available 2008
Sub-type Article (original research)
DOI 10.1080/10428190701817266
Open Access Status Not yet assessed
Volume 49
Issue 3
Start page 517
End page 523
Total pages 27
Place of publication United Kingdom
Publisher Informa Healthcare
Language eng
Subject C1
920102 Cancer and Related Disorders
970111 Expanding Knowledge in the Medical and Health Sciences
111201 Cancer Cell Biology
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 CBFβ/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 ≥1 log10 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 rise. A ≥1 log10 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.
Formatted 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 CBFβ/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 ≥1 log10 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 log10 rise. A ≥1 log10 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.
Keyword Oncology
Hematology
Oncology
Hematology
HEMATOLOGY
ONCOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Wed, 08 Apr 2009, 22:21:41 EST by Amanda Jones on behalf of School of Medicine