-
Blood.
1998 Oct 1;92(7):2322-33.-
Comment in:
- Blood. 2000 Sep 1;96(5):2002.
The importance of diagnostic
cytogenetics on outcome in AML: analysis of 1,612
patients entered into the MRC AML 10 trial. The
Medical Research Council Adult and Children's
Leukaemia Working Parties.
Grimwade D,
Walker H, Oliver F, Wheatley K, Harrison C, Harrison
G, Rees J, Hann I, Stevens R, Burnett A, Goldstone
A. Departments of Haematology, University College
London; the Royal Free and Great Ormond St
Children's Hospitals, London, 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.
PMID: 9746770 [PubMed - indexed for
MEDLINE]