12th Congress of the European Hematology ... - Haematologica

Cytogenetics and molecular diagnostics
0381
KARYOTYPE IS AN INDEPENDENT PROGNOSTIC FACTOR IN ADULT ACUTE
LYMPHOBLASTIC LEUKEMIA
A. Moorman, 1 C.J. Harrison, 1 G.A.N. Buck, 2 S.M. Richards, 2
L.M. Secker-Walker, 1 M. Martineau, 1 G.H. Vance, 3 A.M. Cherry, 4
R.R. Higgins, 5 A.K. Fielding, 6 L. Foroni, 6 E. Paietta, 7 M.S. Tallman, 8 M.R.
Litzow, 9 P.H. Wiernik, 7 J.M. Rowe, 10 A.H. Goldstone, 11
G.W. Dewald9
1 2 University of Southampton, SOUTHAMPTON, United Kingdom; University
of Oxford, OXFORD, United Kingdom; 3Indiana Unversity School of Medicine,
INDIANAPOLIS, USA; 4Stanford University School of Medicine, STAN-
FORD, USA; 5Abbott Northwestern Hospital, MINNEAPOLIS, USA; 6Royal Free and UCMS, LONDON, United Kingdom; 7Our Lady of Mercy Medical
Center, NEW YORK, USA; 8Northwestern University Feinberg, CHICAGO,
USA; 9Mayo Clinic, ROCHESTER, USA; 10Rambam Medical Center, HAIFA,
Israel; 11UCLH, LONDON, United Kingdom
Pre-treatment cytogenetics is a known predictor of outcome in haematological
malignancies. However, its usefulness in adult acute lymphoblastic
leukaemia is generally limited to the presence of the Philadelphia
chromosome (Ph) because of the low incidence of other recurrent
abnormalities and the rarity of the disease in this age group. We present
centrally reviewed cytogenetic data from adult patients enrolled on the
Medical Research Council (MRC) UKALLXII / Eastern Cooperative
Oncology Group (ECOG) 2993 Trial MRC. Cytogenetic analysis was
attempted in 1,366/1,522 (90%) patients. This rate did not vary by registration
centre, year of diagnosis or patient age. Cytogenetic analysis
was successful in 1,003 (73%) cases but was considered unacceptable in
363 (27%) cases. Among those patients with successful cytogenetics an
abnormal clone was detected in 796 (79%). There was no trend towards
a higher rate of unacceptable cytogenetics in the early part of the trial
compared with the later years. Patients were classified according to the
presence of each of the following chromosomal abnormalities:
t(9;22)(q34;q11.2) (Ph) (n=267, 19%); t(4;11)(q21;q23) (n=54, 7%); other
MLL/11q23 translocations (n=15, 2%); t(1;19)(q21;p13.3) (n=24, 3%);
t(8;14)(q24.1;q32) plus variants (n=16, 2%); t(10;14)(q24;q11.2) (n=16,
2%); other T-cell receptor translocations (n=18, 2%); 14q32 translocations
(n=45, 6%); 6q deletions (n=55, 7%); 7p deletions (n=23, 3%); -7
(n=19, 2%); + 8 (n=23, 3%); + X (n=34, 4%); 9p deletions (n=71, 9%);
11q abnormalities (n=29, 4%); 12p deletions (n=29, 4%); -13 / 13q deletions
(n=40, 5%); 17p deletions (n=40, 5%); complex karyotype (five or
more chromosomal abnormalities) (n=41, 5%); low hypodiploidy (30-
39 chromosomes) / near-triploidy (60-78 chromosomes) (Ho-Tr) (n=31,
4%); high hyperdiploidy (51-65 chromosomes) (n=77, 10%); tetraploidy
(80 or more chromosomes) (n=15, 2%); other abnormality (n=102, 13%);
normal karyotype (n=195, 25%). Ph-positive patients had a significantly
inferior 5 year overall survival (OS) compared with Ph-negative
patients: 22% (95% CI 17%-27%) versus 41% (38%-44%) [p=0.0001
adjusting for age, gender and white cell count (WCC)]. Within the Phnegative
cohort, the following four chromosomal abnormalities were
associated with a poorer outcome: t(4;11), OS 24% (13%-36%), p