RESULTS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA PATIENTS WHO FAILED TYROSINE KINASE INHIBITORS
(Abstract release date: 05/19/16)
EHA Library. Moreira Funke V. 06/09/16; 133085; E1536
Disclosure(s): No disclosures
Prof. Vaneuza Araújo Moreira Funke
Contributions
Contributions
Abstract
Abstract: E1536
Type: Eposter Presentation
Background
Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm. The hallmark is the presence of a reciprocal t(9;22)(q34;q11.2) – Philadelphia chromosome (Ph), resulting in which produces a BCR-ABL fusion gene and therefore a BCR-ABL protein with constitutive tyrosine kinase activity. Tyrosine kinase inhibitors (TKI) are the first line of treatment. However, some patients are resistant. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is indicated for patients with Chronic Myelogenous Leukemia (CML) who develop resistance to tyrosine kinase inhibitors (TKI).
Aims
The main aim is analyzing outcomes of HSCT in 49 patients with CML resistant to TKI and identifying risk factors for overall survival (OS) and disease free survival (DFS) in those patients.
Methods
We analyzed the outcomes of 49 patients resistant to TKIs transplanted at the BMT Center of Federal University of Paraná, from January 2001 to August 2015. The study is retrospective, observational and analytical, held from data record in either STMO database or medical chart. Informed consent was waived. Kaplan-Meyer method was used to build survival curves and Log-rank test to compare them. The established level of significance was p <0.05. The following risk factors were analyzed: donor and recipient sex, age at HSCT, pre-HSCT imatinib, second generation inhibitors or interferon, conditioning regimen, immunoprophylaxis, donor type, stem cell source, HLA compatibility, engraftment, acute graft versus host disease (aGVHD), chronic graft versus host disease (cGVHD), disease phase and previous response to TKI (hematologic and cytogenetic). Multivariate analysis was performed using Cox Regression model to identify risk factors for overall survival and disease-free survival.
Results
Chronic graft versus host disease (GVHD) (n=16) was associated to a higher OS (p = 0,04) whereas acute GVHD (n=13) was associated to a lower OS. Regarding to DFS, a myeloablative (MA) conditioning regimen (n=45) lead to higher survival probability (p = 0.00182). BCR-ABL mutation analysis was performed before HSCT in 55 % of the patients (n = 27) and found in 33% (n = 9). The presence of mutations was a significant risk factor for OS (p=0.00366). The median OS was 373 days (33-3677) and the median DFS was 273 days (0-3677). Five years probability of survival was 41% for entire group.
Conclusion
HSCT is an important alternative for patients with TKI resistance. Chronic GVHD was associated with a 3,6 lower probability of death, while occurence of acute GVHD had a negative impact, increasing probability of death in 3 times. Worse outcome was showed for patients with pre-transplant mutations. Myeloablative conditioning was significantly associated with better DFS.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Stem cell transplant
Type: Eposter Presentation
Background
Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm. The hallmark is the presence of a reciprocal t(9;22)(q34;q11.2) – Philadelphia chromosome (Ph), resulting in which produces a BCR-ABL fusion gene and therefore a BCR-ABL protein with constitutive tyrosine kinase activity. Tyrosine kinase inhibitors (TKI) are the first line of treatment. However, some patients are resistant. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is indicated for patients with Chronic Myelogenous Leukemia (CML) who develop resistance to tyrosine kinase inhibitors (TKI).
Aims
The main aim is analyzing outcomes of HSCT in 49 patients with CML resistant to TKI and identifying risk factors for overall survival (OS) and disease free survival (DFS) in those patients.
Methods
We analyzed the outcomes of 49 patients resistant to TKIs transplanted at the BMT Center of Federal University of Paraná, from January 2001 to August 2015. The study is retrospective, observational and analytical, held from data record in either STMO database or medical chart. Informed consent was waived. Kaplan-Meyer method was used to build survival curves and Log-rank test to compare them. The established level of significance was p <0.05. The following risk factors were analyzed: donor and recipient sex, age at HSCT, pre-HSCT imatinib, second generation inhibitors or interferon, conditioning regimen, immunoprophylaxis, donor type, stem cell source, HLA compatibility, engraftment, acute graft versus host disease (aGVHD), chronic graft versus host disease (cGVHD), disease phase and previous response to TKI (hematologic and cytogenetic). Multivariate analysis was performed using Cox Regression model to identify risk factors for overall survival and disease-free survival.
Results
Chronic graft versus host disease (GVHD) (n=16) was associated to a higher OS (p = 0,04) whereas acute GVHD (n=13) was associated to a lower OS. Regarding to DFS, a myeloablative (MA) conditioning regimen (n=45) lead to higher survival probability (p = 0.00182). BCR-ABL mutation analysis was performed before HSCT in 55 % of the patients (n = 27) and found in 33% (n = 9). The presence of mutations was a significant risk factor for OS (p=0.00366). The median OS was 373 days (33-3677) and the median DFS was 273 days (0-3677). Five years probability of survival was 41% for entire group.
Conclusion
HSCT is an important alternative for patients with TKI resistance. Chronic GVHD was associated with a 3,6 lower probability of death, while occurence of acute GVHD had a negative impact, increasing probability of death in 3 times. Worse outcome was showed for patients with pre-transplant mutations. Myeloablative conditioning was significantly associated with better DFS.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Stem cell transplant
Abstract: E1536
Type: Eposter Presentation
Background
Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm. The hallmark is the presence of a reciprocal t(9;22)(q34;q11.2) – Philadelphia chromosome (Ph), resulting in which produces a BCR-ABL fusion gene and therefore a BCR-ABL protein with constitutive tyrosine kinase activity. Tyrosine kinase inhibitors (TKI) are the first line of treatment. However, some patients are resistant. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is indicated for patients with Chronic Myelogenous Leukemia (CML) who develop resistance to tyrosine kinase inhibitors (TKI).
Aims
The main aim is analyzing outcomes of HSCT in 49 patients with CML resistant to TKI and identifying risk factors for overall survival (OS) and disease free survival (DFS) in those patients.
Methods
We analyzed the outcomes of 49 patients resistant to TKIs transplanted at the BMT Center of Federal University of Paraná, from January 2001 to August 2015. The study is retrospective, observational and analytical, held from data record in either STMO database or medical chart. Informed consent was waived. Kaplan-Meyer method was used to build survival curves and Log-rank test to compare them. The established level of significance was p <0.05. The following risk factors were analyzed: donor and recipient sex, age at HSCT, pre-HSCT imatinib, second generation inhibitors or interferon, conditioning regimen, immunoprophylaxis, donor type, stem cell source, HLA compatibility, engraftment, acute graft versus host disease (aGVHD), chronic graft versus host disease (cGVHD), disease phase and previous response to TKI (hematologic and cytogenetic). Multivariate analysis was performed using Cox Regression model to identify risk factors for overall survival and disease-free survival.
Results
Chronic graft versus host disease (GVHD) (n=16) was associated to a higher OS (p = 0,04) whereas acute GVHD (n=13) was associated to a lower OS. Regarding to DFS, a myeloablative (MA) conditioning regimen (n=45) lead to higher survival probability (p = 0.00182). BCR-ABL mutation analysis was performed before HSCT in 55 % of the patients (n = 27) and found in 33% (n = 9). The presence of mutations was a significant risk factor for OS (p=0.00366). The median OS was 373 days (33-3677) and the median DFS was 273 days (0-3677). Five years probability of survival was 41% for entire group.
Conclusion
HSCT is an important alternative for patients with TKI resistance. Chronic GVHD was associated with a 3,6 lower probability of death, while occurence of acute GVHD had a negative impact, increasing probability of death in 3 times. Worse outcome was showed for patients with pre-transplant mutations. Myeloablative conditioning was significantly associated with better DFS.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Stem cell transplant
Type: Eposter Presentation
Background
Chronic Myelogenous Leukemia (CML) is a myeloproliferative neoplasm. The hallmark is the presence of a reciprocal t(9;22)(q34;q11.2) – Philadelphia chromosome (Ph), resulting in which produces a BCR-ABL fusion gene and therefore a BCR-ABL protein with constitutive tyrosine kinase activity. Tyrosine kinase inhibitors (TKI) are the first line of treatment. However, some patients are resistant. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is indicated for patients with Chronic Myelogenous Leukemia (CML) who develop resistance to tyrosine kinase inhibitors (TKI).
Aims
The main aim is analyzing outcomes of HSCT in 49 patients with CML resistant to TKI and identifying risk factors for overall survival (OS) and disease free survival (DFS) in those patients.
Methods
We analyzed the outcomes of 49 patients resistant to TKIs transplanted at the BMT Center of Federal University of Paraná, from January 2001 to August 2015. The study is retrospective, observational and analytical, held from data record in either STMO database or medical chart. Informed consent was waived. Kaplan-Meyer method was used to build survival curves and Log-rank test to compare them. The established level of significance was p <0.05. The following risk factors were analyzed: donor and recipient sex, age at HSCT, pre-HSCT imatinib, second generation inhibitors or interferon, conditioning regimen, immunoprophylaxis, donor type, stem cell source, HLA compatibility, engraftment, acute graft versus host disease (aGVHD), chronic graft versus host disease (cGVHD), disease phase and previous response to TKI (hematologic and cytogenetic). Multivariate analysis was performed using Cox Regression model to identify risk factors for overall survival and disease-free survival.
Results
Chronic graft versus host disease (GVHD) (n=16) was associated to a higher OS (p = 0,04) whereas acute GVHD (n=13) was associated to a lower OS. Regarding to DFS, a myeloablative (MA) conditioning regimen (n=45) lead to higher survival probability (p = 0.00182). BCR-ABL mutation analysis was performed before HSCT in 55 % of the patients (n = 27) and found in 33% (n = 9). The presence of mutations was a significant risk factor for OS (p=0.00366). The median OS was 373 days (33-3677) and the median DFS was 273 days (0-3677). Five years probability of survival was 41% for entire group.
Conclusion
HSCT is an important alternative for patients with TKI resistance. Chronic GVHD was associated with a 3,6 lower probability of death, while occurence of acute GVHD had a negative impact, increasing probability of death in 3 times. Worse outcome was showed for patients with pre-transplant mutations. Myeloablative conditioning was significantly associated with better DFS.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Stem cell transplant
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