MOLECULAR RESPONSE IN ACUTE MYELOID LEUKEMIA WITH WT1 OVEREXPRESSION HAS A STRONG PROGNOSTIC IMPACT IN PATIENS TREATED WITH CHEMOTHERAPY ONLY AND/OR UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION
(Abstract release date: 05/19/16)
EHA Library. Salek C. 06/09/16; 132478; E929
Dr. Cyril Salek
Contributions
Contributions
Abstract
Abstract: E929
Type: Eposter Presentation
Background
WT1 is a leukemia associated antigen whose expression may be used as an alternative marker for minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) mainly in patients lacking a specific molecular target.
Aims
To evaluate the prognostic impact of WT1 expression at diagnosis and during therapy.
Methods
The cohort comprised 84 subjects (median age 52 yrs, range 21-66 yrs; median follow up 1.9 yrs, range 0.6-7.1 yrs) treated from 2008 to 2014 who had overexpressed WT1 gene at diagnosis and attained hematological remission after up to 2 induction cycles of chemotherapy. Consolidation chemotherapy consisted of 3-4 cycles of chemotherapy or allogeneic hematopoetic stem cell transplantation (HSCT), depending on cytogenetic and molecular characteristics and response to the first induction cycle. WT1 expression was quantified using a standardized method according to the recommendations of European LeukemiaNet. Upper normal limit of WT1 expression was defined as ≤50 copies WT1/104 copies of reference gene ABL in peripheral blood. Only patients with WT1 overexpression >500 copies/104 ABL at diagnosis were suitable for MRD monitoring. Molecular response (MR) was defined as a decrease of WT1 expression <50 copies/104 ABL.
Results
Patients with WT1 expression at diagnosis >500 and ≤5000 copies WT1/104 ABL had 3yr OS 70% and EFS 40%, whereas those with >5000 copies had 3yr OS 50% and EFS 25%, respectively (p=0.036 for OS and 0.030 for EFS). Failure to reach MR was a strong prognostic factor for survival in an overal cohort (3yr OS 63% vs 27%, p<0.001; 3yr EFS 38% vs 0%, p<0.001), in patients treated with chemotherapy only (3yr OS 66% vs 34%, p=0.002; 3yr EFS 31% vs 0%, p=0.009) as well as in patients undergoing HSCT in first complete remission (3yr OS 70% vs 30%, p=0.009; 3yr EFS 62% vs 12%, p<0.001). Median time to MR was 3.0 months (95%CI 2.8-3.1) and was not dependent on the level of pre-treatment WT1 expression. Reaching MR before start of consolidation therapy was not signicant (3yr OS 67% vs 51%; p=0.089). Of 43 WT1 positive patients at that timepoint, 33 (77%) reached MR by further therapy (chemotherapy or HSCT). Of 27 patients who were WT1 positive before consolidation I and received another consolidation cycle, 22 (81%) reached MR after consolidation II. There was no significant difference in survival between patients never reaching MR and those with molecular relapse. In a multivariate analysis, the level of WT1 expression at diagnosis and ability to reach MR were significant prognostic factors for OS and EFS. In addition, performing HSCT as part of first line therapy was another positive prognostic factor for EFS only. WT1 expression before HSCT was the only significant marker for OS and EFS in transplanted patients.
Conclusion
The level of WT1 expression at diagnosis correlates with survival. Monitoring of WT1 expression is a sensitive tool for MRD monitoring in patiens with WT1 overexpression at diagnosis. Failure to reach MR is a potent predictor of relapse. These patients could profit from further intensification of the therapy.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Molecular response, Prognostic factor, WT1
Type: Eposter Presentation
Background
WT1 is a leukemia associated antigen whose expression may be used as an alternative marker for minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) mainly in patients lacking a specific molecular target.
Aims
To evaluate the prognostic impact of WT1 expression at diagnosis and during therapy.
Methods
The cohort comprised 84 subjects (median age 52 yrs, range 21-66 yrs; median follow up 1.9 yrs, range 0.6-7.1 yrs) treated from 2008 to 2014 who had overexpressed WT1 gene at diagnosis and attained hematological remission after up to 2 induction cycles of chemotherapy. Consolidation chemotherapy consisted of 3-4 cycles of chemotherapy or allogeneic hematopoetic stem cell transplantation (HSCT), depending on cytogenetic and molecular characteristics and response to the first induction cycle. WT1 expression was quantified using a standardized method according to the recommendations of European LeukemiaNet. Upper normal limit of WT1 expression was defined as ≤50 copies WT1/104 copies of reference gene ABL in peripheral blood. Only patients with WT1 overexpression >500 copies/104 ABL at diagnosis were suitable for MRD monitoring. Molecular response (MR) was defined as a decrease of WT1 expression <50 copies/104 ABL.
Results
Patients with WT1 expression at diagnosis >500 and ≤5000 copies WT1/104 ABL had 3yr OS 70% and EFS 40%, whereas those with >5000 copies had 3yr OS 50% and EFS 25%, respectively (p=0.036 for OS and 0.030 for EFS). Failure to reach MR was a strong prognostic factor for survival in an overal cohort (3yr OS 63% vs 27%, p<0.001; 3yr EFS 38% vs 0%, p<0.001), in patients treated with chemotherapy only (3yr OS 66% vs 34%, p=0.002; 3yr EFS 31% vs 0%, p=0.009) as well as in patients undergoing HSCT in first complete remission (3yr OS 70% vs 30%, p=0.009; 3yr EFS 62% vs 12%, p<0.001). Median time to MR was 3.0 months (95%CI 2.8-3.1) and was not dependent on the level of pre-treatment WT1 expression. Reaching MR before start of consolidation therapy was not signicant (3yr OS 67% vs 51%; p=0.089). Of 43 WT1 positive patients at that timepoint, 33 (77%) reached MR by further therapy (chemotherapy or HSCT). Of 27 patients who were WT1 positive before consolidation I and received another consolidation cycle, 22 (81%) reached MR after consolidation II. There was no significant difference in survival between patients never reaching MR and those with molecular relapse. In a multivariate analysis, the level of WT1 expression at diagnosis and ability to reach MR were significant prognostic factors for OS and EFS. In addition, performing HSCT as part of first line therapy was another positive prognostic factor for EFS only. WT1 expression before HSCT was the only significant marker for OS and EFS in transplanted patients.
Conclusion
The level of WT1 expression at diagnosis correlates with survival. Monitoring of WT1 expression is a sensitive tool for MRD monitoring in patiens with WT1 overexpression at diagnosis. Failure to reach MR is a potent predictor of relapse. These patients could profit from further intensification of the therapy.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Molecular response, Prognostic factor, WT1
Abstract: E929
Type: Eposter Presentation
Background
WT1 is a leukemia associated antigen whose expression may be used as an alternative marker for minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) mainly in patients lacking a specific molecular target.
Aims
To evaluate the prognostic impact of WT1 expression at diagnosis and during therapy.
Methods
The cohort comprised 84 subjects (median age 52 yrs, range 21-66 yrs; median follow up 1.9 yrs, range 0.6-7.1 yrs) treated from 2008 to 2014 who had overexpressed WT1 gene at diagnosis and attained hematological remission after up to 2 induction cycles of chemotherapy. Consolidation chemotherapy consisted of 3-4 cycles of chemotherapy or allogeneic hematopoetic stem cell transplantation (HSCT), depending on cytogenetic and molecular characteristics and response to the first induction cycle. WT1 expression was quantified using a standardized method according to the recommendations of European LeukemiaNet. Upper normal limit of WT1 expression was defined as ≤50 copies WT1/104 copies of reference gene ABL in peripheral blood. Only patients with WT1 overexpression >500 copies/104 ABL at diagnosis were suitable for MRD monitoring. Molecular response (MR) was defined as a decrease of WT1 expression <50 copies/104 ABL.
Results
Patients with WT1 expression at diagnosis >500 and ≤5000 copies WT1/104 ABL had 3yr OS 70% and EFS 40%, whereas those with >5000 copies had 3yr OS 50% and EFS 25%, respectively (p=0.036 for OS and 0.030 for EFS). Failure to reach MR was a strong prognostic factor for survival in an overal cohort (3yr OS 63% vs 27%, p<0.001; 3yr EFS 38% vs 0%, p<0.001), in patients treated with chemotherapy only (3yr OS 66% vs 34%, p=0.002; 3yr EFS 31% vs 0%, p=0.009) as well as in patients undergoing HSCT in first complete remission (3yr OS 70% vs 30%, p=0.009; 3yr EFS 62% vs 12%, p<0.001). Median time to MR was 3.0 months (95%CI 2.8-3.1) and was not dependent on the level of pre-treatment WT1 expression. Reaching MR before start of consolidation therapy was not signicant (3yr OS 67% vs 51%; p=0.089). Of 43 WT1 positive patients at that timepoint, 33 (77%) reached MR by further therapy (chemotherapy or HSCT). Of 27 patients who were WT1 positive before consolidation I and received another consolidation cycle, 22 (81%) reached MR after consolidation II. There was no significant difference in survival between patients never reaching MR and those with molecular relapse. In a multivariate analysis, the level of WT1 expression at diagnosis and ability to reach MR were significant prognostic factors for OS and EFS. In addition, performing HSCT as part of first line therapy was another positive prognostic factor for EFS only. WT1 expression before HSCT was the only significant marker for OS and EFS in transplanted patients.
Conclusion
The level of WT1 expression at diagnosis correlates with survival. Monitoring of WT1 expression is a sensitive tool for MRD monitoring in patiens with WT1 overexpression at diagnosis. Failure to reach MR is a potent predictor of relapse. These patients could profit from further intensification of the therapy.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Molecular response, Prognostic factor, WT1
Type: Eposter Presentation
Background
WT1 is a leukemia associated antigen whose expression may be used as an alternative marker for minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) mainly in patients lacking a specific molecular target.
Aims
To evaluate the prognostic impact of WT1 expression at diagnosis and during therapy.
Methods
The cohort comprised 84 subjects (median age 52 yrs, range 21-66 yrs; median follow up 1.9 yrs, range 0.6-7.1 yrs) treated from 2008 to 2014 who had overexpressed WT1 gene at diagnosis and attained hematological remission after up to 2 induction cycles of chemotherapy. Consolidation chemotherapy consisted of 3-4 cycles of chemotherapy or allogeneic hematopoetic stem cell transplantation (HSCT), depending on cytogenetic and molecular characteristics and response to the first induction cycle. WT1 expression was quantified using a standardized method according to the recommendations of European LeukemiaNet. Upper normal limit of WT1 expression was defined as ≤50 copies WT1/104 copies of reference gene ABL in peripheral blood. Only patients with WT1 overexpression >500 copies/104 ABL at diagnosis were suitable for MRD monitoring. Molecular response (MR) was defined as a decrease of WT1 expression <50 copies/104 ABL.
Results
Patients with WT1 expression at diagnosis >500 and ≤5000 copies WT1/104 ABL had 3yr OS 70% and EFS 40%, whereas those with >5000 copies had 3yr OS 50% and EFS 25%, respectively (p=0.036 for OS and 0.030 for EFS). Failure to reach MR was a strong prognostic factor for survival in an overal cohort (3yr OS 63% vs 27%, p<0.001; 3yr EFS 38% vs 0%, p<0.001), in patients treated with chemotherapy only (3yr OS 66% vs 34%, p=0.002; 3yr EFS 31% vs 0%, p=0.009) as well as in patients undergoing HSCT in first complete remission (3yr OS 70% vs 30%, p=0.009; 3yr EFS 62% vs 12%, p<0.001). Median time to MR was 3.0 months (95%CI 2.8-3.1) and was not dependent on the level of pre-treatment WT1 expression. Reaching MR before start of consolidation therapy was not signicant (3yr OS 67% vs 51%; p=0.089). Of 43 WT1 positive patients at that timepoint, 33 (77%) reached MR by further therapy (chemotherapy or HSCT). Of 27 patients who were WT1 positive before consolidation I and received another consolidation cycle, 22 (81%) reached MR after consolidation II. There was no significant difference in survival between patients never reaching MR and those with molecular relapse. In a multivariate analysis, the level of WT1 expression at diagnosis and ability to reach MR were significant prognostic factors for OS and EFS. In addition, performing HSCT as part of first line therapy was another positive prognostic factor for EFS only. WT1 expression before HSCT was the only significant marker for OS and EFS in transplanted patients.
Conclusion
The level of WT1 expression at diagnosis correlates with survival. Monitoring of WT1 expression is a sensitive tool for MRD monitoring in patiens with WT1 overexpression at diagnosis. Failure to reach MR is a potent predictor of relapse. These patients could profit from further intensification of the therapy.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Molecular response, Prognostic factor, WT1
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