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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2322-2333
The Importance of Diagnostic Cytogenetics on Outcome in AML:
Analysis of 1,612 Patients Entered Into the MRC AML 10 Trial
David Grimwade,
Helen Walker,
Fiona Oliver,
Keith Wheatley,
Christine Harrison,
Georgina Harrison,
John Rees,
Ian Hann,
Richard Stevens,
Alan Burnett, and
Anthony Goldstone on behalf of the Medical
Research Council Adult and Children's Leukaemia Working Parties
From the Departments of Haematology, University College London; the
Royal Free and Great Ormond St Children's Hospitals, London; Royal
Manchester Children's Hospital, Manchester; University of Cambridge
and University of Wales College of Medicine, Cardiff; the Division of
Medical and Molecular Genetics, United Medical and Dental Schools of
Guy's and St Thomas's Hospitals, London; and the Clinical Trial
Service Unit, Radcliffe Infirmary, Oxford, UK.
Cytogenetics is considered one of the most valuable prognostic
determinants in acute myeloid leukemia (AML). However, many studies on
which this assertion is based were limited by relatively small sample
sizes or varying treatment approach, leading to conflicting data
regarding the prognostic implications of specific cytogenetic abnormalities. The Medical Research Council (MRC) AML 10 trial, which
included children and adults up to 55 years of age, not only affords
the opportunity to determine the independent prognostic significance of
pretreatment cytogenetics in the context of large patient groups
receiving comparable therapy, but also to address their impact on the
outcome of subsequent transplantation procedures performed in first
complete remission (CR). On the basis of response to induction
treatment, relapse risk, and overall survival, three prognostic groups
could be defined by cytogenetic abnormalities detected at presentation
in comparison with the outcome of patients with normal karyotype. AML
associated with t(8;21), t(15;17) or inv(16) predicted a relatively
favorable outcome. Whereas in patients lacking these favorable changes,
the presence of a complex karyotype,  5, del(5q), 7, or
abnormalities of 3q defined a group with relatively poor prognosis. The
remaining group of patients including those with 11q23 abnormalities,
+8, +21, +22, del(9q), del(7q) or other miscellaneous structural
or numerical defects not encompassed by the favorable or adverse risk
groups were found to have an intermediate prognosis. The presence of
additional cytogenetic abnormalities did not modify the outcome of
patients with favorable cytogenetics. Subgroup analysis demonstrated
that the three cytogenetically defined prognostic groups retained their
predictive value in the context of secondary as well as de novo AML,
within the pediatric age group and furthermore were found to be a key
determinant of outcome from autologous or allogeneic bone marrow
transplantation (BMT) in first CR. This study highlights the importance
of diagnostic cytogenetics as an independent prognostic factor in AML,
providing the framework for a stratified treatment approach of this
disease, which has been adopted in the current MRC AML 12 trial.
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