International Journal of Hematology-Oncology and Stem Cell Research 2017. 11(1):30-36.

Characterization of Patients with Chronic Myeloid Leukemia Unresponsive to Tyrosine Kinase Inhibitors who Underwent Allogeneic Hematopoietic Stem Cell Transplantation
Franceli Carvalho, Joice Zuckermann, Alessandra Paz, Gustavo Fischer, Liane Esteves Daudt, Lisandra Della Costa Rigoni, Lúcia Silla, Laura Fogliatto, Simone Martins de Castro, Diogo André Pilger

Abstract


Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure.

Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014.

Results: Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT.

Conclusion: The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT.


Keywords


Chronic myeloid leukemia; Tyrosine kinase inhibitors; Resistance; Intolerance

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