CLINICAL SIGNIFICANCE OF IMMUNOPHENOTYPIC CHANGES AT THE FIRST RELAPSE IN ADULT ACUTE MYELOID LEUKEMIA PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Shimizu H. 06/09/16; 134554; PB1654
Dr. Hiroaki Shimizu
Contributions
Contributions
Abstract
Abstract: PB1654
Type: Publication Only
Background
Immunophenotypic changes (IPC) between diagnosis and the first relapse are found in up to 90% of relapsed acute myeloid leukemia (AML) cases, and are considered as a result of major clone shift and/or clonal evolution of AML cells, just like additional cytogenetic abnormality (ACA) which we reported that was the strongest negative prognostic factor in relapsed AML patients.
Aims
Because the clinical significance of IPC has not been elucidated in adult AML patients, we conducted a large-scale retrospective study to address this unsolved issue.
Methods
Of the 375 adult patients diagnosed with non-APL AML between 1990 and 2010, 108 relapsed patients whose immunophenotypic data both at diagnosis and at the first relapse were available were included in this study. All these patients underwent intensive chemotherapy. AML cells were sorted with usual CD45/SSC gating, and CD7, CD19, CD13, CD33, CD34, HLA-DR, and CD56 were analyzed. IPC was diagnosed when more than 50% increase or decrease of at least one antigen-positive from diagnosis to the first relapse was observed. Overall survival (OS) was defined as the interval from the date of the first relapse to the date of death. Fisher’s exact test was used to compare binary variables. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Multiple logistic regression analysis and the Cox proportional hazard model were used for multivariate analysis of predisposing factors and prognostic factors, respectively. Values of p < 0.05 were considered to indicate statistical significance.
Results
Of the 108 patients included in this study, 65 patients were male, and 43 were female. The median age was 56 years (range, 18–78 years). According to the definition described above, 46 patients (43%) experienced IPC at the first relapse. With univariate analysis, t(8;21) was extracted as a statistically significant predisposing factor for IPC at the first relapse (69%). Multivariate analysis revealed t(8;21) and M4/5 as independent predisposing factors. Excluding one patient that directly proceeded to allo-SCT without re-induction chemotherapy, the 107 patients with IPC showed a similar second remission rate when comparing with those without IPC (42.1% vs. 44.0%, respectively; p = 0.848). Additionally, among all 108 patients, there was no significant difference in the 2-year OS rates after the first relapse between patients with and without IPC (34.4% vs. 29.3%, respectively; p = 0.212). Multivariate analysis extracted ACA, high-risk karyotype, fewer than 12 months duration of the first remission, and no allogeneic stem cell transplantation (allo-SCT) after the first relapse, but not IPC. Of the 46 patients with IPC (median age: 55, range; 18–78 years), 18 underwent allo-SCT after the first relapse. The 2-year OS rates after the first relapse were significantly different between patients undergoing allo-SCT after the first relapse and those treated only with chemotherapy (62.7% vs. 17.9%; p < 0.001). With multivariate analysis, undergoing allo-SCT after the first relapse was identified as an independent prognostic factor, in addition to ACA and duration of the first remission.
Conclusion
These findings suggested that IPC had no prognostic impact in relapsed AML patients, unlike acquisition of ACA. As t(8;21) was extracted as an independent predisposing factor for IPC as well as ACA, susceptibility for clonal evolution might be high in t(8;21) AML patients. Clarification of the biological background of IPC may contribute to the development of novel therapeutic strategies and improved treatment outcomes in adult AML patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Clonal expansion, Immunophenotype
Type: Publication Only
Background
Immunophenotypic changes (IPC) between diagnosis and the first relapse are found in up to 90% of relapsed acute myeloid leukemia (AML) cases, and are considered as a result of major clone shift and/or clonal evolution of AML cells, just like additional cytogenetic abnormality (ACA) which we reported that was the strongest negative prognostic factor in relapsed AML patients.
Aims
Because the clinical significance of IPC has not been elucidated in adult AML patients, we conducted a large-scale retrospective study to address this unsolved issue.
Methods
Of the 375 adult patients diagnosed with non-APL AML between 1990 and 2010, 108 relapsed patients whose immunophenotypic data both at diagnosis and at the first relapse were available were included in this study. All these patients underwent intensive chemotherapy. AML cells were sorted with usual CD45/SSC gating, and CD7, CD19, CD13, CD33, CD34, HLA-DR, and CD56 were analyzed. IPC was diagnosed when more than 50% increase or decrease of at least one antigen-positive from diagnosis to the first relapse was observed. Overall survival (OS) was defined as the interval from the date of the first relapse to the date of death. Fisher’s exact test was used to compare binary variables. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Multiple logistic regression analysis and the Cox proportional hazard model were used for multivariate analysis of predisposing factors and prognostic factors, respectively. Values of p < 0.05 were considered to indicate statistical significance.
Results
Of the 108 patients included in this study, 65 patients were male, and 43 were female. The median age was 56 years (range, 18–78 years). According to the definition described above, 46 patients (43%) experienced IPC at the first relapse. With univariate analysis, t(8;21) was extracted as a statistically significant predisposing factor for IPC at the first relapse (69%). Multivariate analysis revealed t(8;21) and M4/5 as independent predisposing factors. Excluding one patient that directly proceeded to allo-SCT without re-induction chemotherapy, the 107 patients with IPC showed a similar second remission rate when comparing with those without IPC (42.1% vs. 44.0%, respectively; p = 0.848). Additionally, among all 108 patients, there was no significant difference in the 2-year OS rates after the first relapse between patients with and without IPC (34.4% vs. 29.3%, respectively; p = 0.212). Multivariate analysis extracted ACA, high-risk karyotype, fewer than 12 months duration of the first remission, and no allogeneic stem cell transplantation (allo-SCT) after the first relapse, but not IPC. Of the 46 patients with IPC (median age: 55, range; 18–78 years), 18 underwent allo-SCT after the first relapse. The 2-year OS rates after the first relapse were significantly different between patients undergoing allo-SCT after the first relapse and those treated only with chemotherapy (62.7% vs. 17.9%; p < 0.001). With multivariate analysis, undergoing allo-SCT after the first relapse was identified as an independent prognostic factor, in addition to ACA and duration of the first remission.
Conclusion
These findings suggested that IPC had no prognostic impact in relapsed AML patients, unlike acquisition of ACA. As t(8;21) was extracted as an independent predisposing factor for IPC as well as ACA, susceptibility for clonal evolution might be high in t(8;21) AML patients. Clarification of the biological background of IPC may contribute to the development of novel therapeutic strategies and improved treatment outcomes in adult AML patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Clonal expansion, Immunophenotype
Abstract: PB1654
Type: Publication Only
Background
Immunophenotypic changes (IPC) between diagnosis and the first relapse are found in up to 90% of relapsed acute myeloid leukemia (AML) cases, and are considered as a result of major clone shift and/or clonal evolution of AML cells, just like additional cytogenetic abnormality (ACA) which we reported that was the strongest negative prognostic factor in relapsed AML patients.
Aims
Because the clinical significance of IPC has not been elucidated in adult AML patients, we conducted a large-scale retrospective study to address this unsolved issue.
Methods
Of the 375 adult patients diagnosed with non-APL AML between 1990 and 2010, 108 relapsed patients whose immunophenotypic data both at diagnosis and at the first relapse were available were included in this study. All these patients underwent intensive chemotherapy. AML cells were sorted with usual CD45/SSC gating, and CD7, CD19, CD13, CD33, CD34, HLA-DR, and CD56 were analyzed. IPC was diagnosed when more than 50% increase or decrease of at least one antigen-positive from diagnosis to the first relapse was observed. Overall survival (OS) was defined as the interval from the date of the first relapse to the date of death. Fisher’s exact test was used to compare binary variables. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Multiple logistic regression analysis and the Cox proportional hazard model were used for multivariate analysis of predisposing factors and prognostic factors, respectively. Values of p < 0.05 were considered to indicate statistical significance.
Results
Of the 108 patients included in this study, 65 patients were male, and 43 were female. The median age was 56 years (range, 18–78 years). According to the definition described above, 46 patients (43%) experienced IPC at the first relapse. With univariate analysis, t(8;21) was extracted as a statistically significant predisposing factor for IPC at the first relapse (69%). Multivariate analysis revealed t(8;21) and M4/5 as independent predisposing factors. Excluding one patient that directly proceeded to allo-SCT without re-induction chemotherapy, the 107 patients with IPC showed a similar second remission rate when comparing with those without IPC (42.1% vs. 44.0%, respectively; p = 0.848). Additionally, among all 108 patients, there was no significant difference in the 2-year OS rates after the first relapse between patients with and without IPC (34.4% vs. 29.3%, respectively; p = 0.212). Multivariate analysis extracted ACA, high-risk karyotype, fewer than 12 months duration of the first remission, and no allogeneic stem cell transplantation (allo-SCT) after the first relapse, but not IPC. Of the 46 patients with IPC (median age: 55, range; 18–78 years), 18 underwent allo-SCT after the first relapse. The 2-year OS rates after the first relapse were significantly different between patients undergoing allo-SCT after the first relapse and those treated only with chemotherapy (62.7% vs. 17.9%; p < 0.001). With multivariate analysis, undergoing allo-SCT after the first relapse was identified as an independent prognostic factor, in addition to ACA and duration of the first remission.
Conclusion
These findings suggested that IPC had no prognostic impact in relapsed AML patients, unlike acquisition of ACA. As t(8;21) was extracted as an independent predisposing factor for IPC as well as ACA, susceptibility for clonal evolution might be high in t(8;21) AML patients. Clarification of the biological background of IPC may contribute to the development of novel therapeutic strategies and improved treatment outcomes in adult AML patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Clonal expansion, Immunophenotype
Type: Publication Only
Background
Immunophenotypic changes (IPC) between diagnosis and the first relapse are found in up to 90% of relapsed acute myeloid leukemia (AML) cases, and are considered as a result of major clone shift and/or clonal evolution of AML cells, just like additional cytogenetic abnormality (ACA) which we reported that was the strongest negative prognostic factor in relapsed AML patients.
Aims
Because the clinical significance of IPC has not been elucidated in adult AML patients, we conducted a large-scale retrospective study to address this unsolved issue.
Methods
Of the 375 adult patients diagnosed with non-APL AML between 1990 and 2010, 108 relapsed patients whose immunophenotypic data both at diagnosis and at the first relapse were available were included in this study. All these patients underwent intensive chemotherapy. AML cells were sorted with usual CD45/SSC gating, and CD7, CD19, CD13, CD33, CD34, HLA-DR, and CD56 were analyzed. IPC was diagnosed when more than 50% increase or decrease of at least one antigen-positive from diagnosis to the first relapse was observed. Overall survival (OS) was defined as the interval from the date of the first relapse to the date of death. Fisher’s exact test was used to compare binary variables. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Multiple logistic regression analysis and the Cox proportional hazard model were used for multivariate analysis of predisposing factors and prognostic factors, respectively. Values of p < 0.05 were considered to indicate statistical significance.
Results
Of the 108 patients included in this study, 65 patients were male, and 43 were female. The median age was 56 years (range, 18–78 years). According to the definition described above, 46 patients (43%) experienced IPC at the first relapse. With univariate analysis, t(8;21) was extracted as a statistically significant predisposing factor for IPC at the first relapse (69%). Multivariate analysis revealed t(8;21) and M4/5 as independent predisposing factors. Excluding one patient that directly proceeded to allo-SCT without re-induction chemotherapy, the 107 patients with IPC showed a similar second remission rate when comparing with those without IPC (42.1% vs. 44.0%, respectively; p = 0.848). Additionally, among all 108 patients, there was no significant difference in the 2-year OS rates after the first relapse between patients with and without IPC (34.4% vs. 29.3%, respectively; p = 0.212). Multivariate analysis extracted ACA, high-risk karyotype, fewer than 12 months duration of the first remission, and no allogeneic stem cell transplantation (allo-SCT) after the first relapse, but not IPC. Of the 46 patients with IPC (median age: 55, range; 18–78 years), 18 underwent allo-SCT after the first relapse. The 2-year OS rates after the first relapse were significantly different between patients undergoing allo-SCT after the first relapse and those treated only with chemotherapy (62.7% vs. 17.9%; p < 0.001). With multivariate analysis, undergoing allo-SCT after the first relapse was identified as an independent prognostic factor, in addition to ACA and duration of the first remission.
Conclusion
These findings suggested that IPC had no prognostic impact in relapsed AML patients, unlike acquisition of ACA. As t(8;21) was extracted as an independent predisposing factor for IPC as well as ACA, susceptibility for clonal evolution might be high in t(8;21) AML patients. Clarification of the biological background of IPC may contribute to the development of novel therapeutic strategies and improved treatment outcomes in adult AML patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Clonal expansion, Immunophenotype
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