BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase inhibitors and impact on survival.
This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.
a 1 Hemocentro-UNICAMP , University of Campinas, Campinas , São Paulo, Brazil.
Katia Borgia Barbosa
KB
Pagnano
b 2 Laboratório de Biologia Tumoral , University of São Paulo, São Paulo , São Paulo, Brazil.
Israel
I
Bendit
c 3 Hemorio, Rio de Janeiro , Rio de Janeiro, Brazil.
Carla
C
Boquimpani
a 1 Hemocentro-UNICAMP , University of Campinas, Campinas , São Paulo, Brazil.
Carmino Antonio
CA
De Souza
a 1 Hemocentro-UNICAMP , University of Campinas, Campinas , São Paulo, Brazil.
Eliana C M
EC
Miranda
d 4 Instituto Nacional do Câncer, Rio de Janeiro , Rio de Janeiro, Brazil.
Ilana
I
Zalcberg
e 5 Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina de Buenos Aires , Buenos Aires, Argentina.
Irene
I
Larripa
b 2 Laboratório de Biologia Tumoral , University of São Paulo, São Paulo , São Paulo, Brazil.
Luciana
L
Nardinelli
a 1 Hemocentro-UNICAMP , University of Campinas, Campinas , São Paulo, Brazil.
Rosana Antunes
RA
Silveira
f 6 Hospital das Clínicas de Porto Alegre, Porto Alegre , Rio Grande do Sul, Brazil.
Laura
L
Fogliatto
g 7 Federal University of Rio de Janeiro , Rio de Janeiro , Rio de Janeiro, Brazil.
Nelson
N
Spector
h 8 Universidade Federal do Paraná , Curitiba, Paraná, Brazil.
Vaneuza
V
Funke
h 8 Universidade Federal do Paraná , Curitiba, Paraná, Brazil.
Ricardo
R
Pasquini
i 9 Santa Casa de São Paulo, São Paulo , São Paulo, Brazil.
Vania
V
Hungria
i 9 Santa Casa de São Paulo, São Paulo , São Paulo, Brazil.
Carlos Sérgio
CS
Chiattone
j 10 Universidade Federal de Minas Gerais , Belo Horizonte , Minas Gerais, Brazil.
Nelma
N
Clementino
k 11 Hospital Santa Marcelina , São Paulo, São Paulo, Brazil.
Monika
M
Conchon
l 12 Hospital Ramos Mejía , Buenos Aires, Argentina.
Elena Beatriz
EB
Moiraghi
m 13 Banco Municipal de Sangre del DC , Caracas, Venezuela.
Jose Luis
JL
Lopez
n 14 FUNDALEU , Buenos Aires, Argentina.
Carolina
C
Pavlovsky
n 14 FUNDALEU , Buenos Aires, Argentina.
Miguel A
MA
Pavlovsky
o 15 INCAN , Mexico, D.F., Mexico.
Eduardo E
EE
Cervera
p 16 Centro Médico Nacional Siglo XXI , Mexico, D.F., Mexico.
Luis Antonio
LA
Meillon
q 17 University of São Paulo , Ribeirão Preto, São Paulo, Brazil.
Belinda
B
Simões
r 18 Hospital Israelita Albert Einstein , São Paulo, São Paulo, Brazil.
Nelson
N
Hamerschlak
s 19 Hospital Maciel , Montevideo, Uruguay.
Alicia Helena Magarinos
AH
Bozzano
t 20 Instituto Oncologico Nacional , Panamá, Panama.
Ernesto
E
Mayta
u 21 MD Anderson Cancer Center , Houston, Texas, USA.
Jorge
J
Cortes
e 5 Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina de Buenos Aires , Buenos Aires, Argentina.
Raquel M
RM
Bengió
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D016313:Genes, abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D055815:Young Adult
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases
BCR-ABL mutations; Chronic myeloid leukemia; Imatinib; Resistance; Tyrosine kinase inhibitors