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 we...

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Bibliographic Details
Published in:Cancer investigation 2015, Vol.33 (9), p.451
Main Authors: Pagnano, Katia Borgia Barbosa, Bendit, Israel, Boquimpani, Carla, De Souza, Carmino Antonio, Miranda, Eliana C M, Zalcberg, Ilana, Larripa, Irene, Nardinelli, Luciana, Silveira, Rosana Antunes, Fogliatto, Laura, Spector, Nelson, Funke, Vaneuza, Pasquini, Ricardo, Hungria, Vania, Chiattone, Carlos Sérgio, Clementino, Nelma, Conchon, Monika, Moiraghi, Elena Beatriz, Lopez, Jose Luis, Pavlovsky, Carolina, Pavlovsky, Miguel A, Cervera, Eduardo E, Meillon, Luis Antonio, Simões, Belinda, Hamerschlak, Nelson, Bozzano, Alicia Helena Magarinos, Mayta, Ernesto, Cortes, Jorge, Bengió, Raquel M
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents - therapeutic use
Child
Child, Preschool
Disease-Free Survival
Female
Genes, abl - genetics
Humans
Imatinib Mesylate - therapeutic use
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology
Male
Middle Aged
Mutation - genetics
Prognosis
Protein Kinase Inhibitors - therapeutic use
Protein-Tyrosine Kinases - antagonists & inhibitors
Retrospective Studies
Young Adult
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Summary: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.
ISSN:1532-4192