Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis.
Additional chromosomal abnormalities (ACAs) in Philadelphia-positive cells have been reported in ∼ 5% of patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). Few studies addressing the prognostic significance of baseline ACAs in patients treated with imatinib have been published previously. The European LeukemiaNet recommendations suggest that the presence of ACAs at diagnosis is a "warning" for patients in early CP, but there is not much information about their outcome after therapy with tyrosine kinase inhibitors. To investigate the role of ACAs in early CP CML patients treated with imatinib mesylate, we performed an analysis in a large series of 559 patients enrolled in 3 prospective trials of the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on CML: 378 patients were evaluable and ACAs occurred in 21 patients (5.6%). The overall cytogenetic and molecular response rates were significantly lower and the time to response was significantly longer in patients with ACAs. The long-term outcome of patients with ACAs was inferior, but the differences were not significant. The prognostic significance of each specific cytogenetic abnormality was not assessable. Therefore, we confirm that ACAs constitute an adverse prognostic factor in CML patients treated with imatinib as frontline therapy.
Department of Hematology and Oncology L. e A. Seràgnoli, University of Bologna, Bologna, Italy.
Simona
S
Luatti
Fausto
F
Castagnetti
Giulia
G
Marzocchi
Carmen
C
Baldazzi
Gabriele
G
Gugliotta
Ilaria
I
Iacobucci
Giorgina
G
Specchia
Lucia
L
Zanatta
Giovanna
G
Rege-Cambrin
Rege
R
Cambrin
Marco
M
Mancini
Elisabetta
E
Abruzzese
Alfonso
A
Zaccaria
Maria Grazia
MG
Grimoldi
Alessandro
A
Gozzetti
Gaia
G
Ameli
Maria Adele
MA
Capucci
Giandomenico
G
Palka
Paolo
P
Bernasconi
Francesca
F
Palandri
Fabrizio
F
Pane
Giuseppe
G
Saglio
Giovanni
G
Martinelli
Gianantonio
G
Rosti
Michele
M
Baccarani
Nicoletta
N
Testoni
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001549:Benzamides; D002869:Chromosome Aberrations / Q000139:chemically induced*; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000009:adverse effects*; D011379:Prognosis; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate