Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia.
BACKGROUND
Recent advances in genetic characterization of acute myeloid leukemia indicate that combined cytogenetic and molecular analyses provide better definition of prognostic groups. The aim of this study was to verify this prospectively in a large group of patients.


METHODS
Genetic characterization was prospectively carried out in 397 patients with acute myeloid leukemia (median age, 46 years) receiving uniform treatment according to the LAM99P protocol of the Italian GIMEMA group. The impact of genetic markers on response to therapy and outcome was assessed by univariate and multivariate analyses.


RESULTS
For induction response, conventional karyotyping identified three groups with complete remission rates of 92%, 67% and 39% (p<0.0001). Complete remission rates in NPM1 mutated (NPM1+) and wild-type (NPM1-) groups were 76% and 60%, respectively, for the whole population and 81% and 61% in the group with normal karyotype (p<0.001 and p=0.026, respectively). Multivariate analysis indicated that low risk karyotype and NPM1+ were independent factors favorably affecting complete remission. Multivariate analysis of overall and disease-free survival among 269 patients who achieved complete remission showed a significant impact of karyotype on both estimates and of FLT3 status on disease free-survival (FLT3-ITD vs. FLT3 wild-type, p=0.0001). NPM1 status did not significantly influence disease free-survival in either the whole population or in the patients with a normal karyotype in this series, probably due to the low number of cases analyzed.


CONCLUSIONS
These results reiterate the prognostic relevance of combining cytogenetic and mutational analysis in the diagnostic work up of patients with acute myeloid leukemia.
Department of Biopathology, University Tor Vergata, via Montpellier 1, 00161 Rome, Italy. francesco.lo.coco@uniroma2.it
Francesco
F
Lo-Coco
Antonio
A
Cuneo
Fabrizio
F
Pane
Daniela
D
Cilloni
Daniela
D
Diverio
Marco
M
Mancini
Nicoletta
N
Testoni
Antonella
A
Bardi
Barbara
B
Izzo
Niccolò
N
Bolli
Roberta
R
La Starza
Paola
P
Fazi
Simona
S
Iacobelli
Alfonso
A
Piciocchi
Marco
M
Vignetti
Sergio
S
Amadori
Franco
F
Mandelli
Pier Giuseppe
PG
Pelicci
Cristina
C
Mecucci
Brunangelo
B
Falini
Giuseppe
G
Saglio
D000293:Adolescent; D000328:Adult; D003582:Cytogenetics; D004252:DNA Mutational Analysis; D005819:Genetic Markers; D006801:Humans; D007558:Italy; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction
D005819:Genetic Markers; C000716967:NPM1 protein, human; D000090243:Nucleophosmin