Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.
The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.
Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
Alice
A
Fabarius
Armin
A
Leitner
Andreas
A
Hochhaus
Martin C
MC
Müller
Benjamin
B
Hanfstein
Claudia
C
Haferlach
Gudrun
G
Göhring
Brigitte
B
Schlegelberger
Martine
M
Jotterand
Andreas
A
Reiter
Susanne
S
Jung-Munkwitz
Ulrike
U
Proetel
Juliana
J
Schwaab
Wolf-Karsten
WK
Hofmann
Jörg
J
Schubert
Hermann
H
Einsele
Anthony D
AD
Ho
Christiane
C
Falge
Lothar
L
Kanz
Andreas
A
Neubauer
Michael
M
Kneba
Frank
F
Stegelmann
Michael
M
Pfreundschuh
Cornelius F
CF
Waller
Karsten
K
Spiekermann
Gabriela M
GM
Baerlocher
Michael
M
Lauseker
Markus
M
Pfirrmann
Joerg
J
Hasford
Susanne
S
Saussele
Rüdiger
R
Hehlmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014314:Trisomy; D055815:Young Adult