BCR-ABL1 TRANSCRIPT LEVEL HALVING TIME IS THE ULTIMATE PROGNOSTIC FACTOR FOR ACHIEVING MAJOR AND DEEP MOLECULAR RESPONSE IN CML PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Gniot M. 06/09/16; 132650; E1101
Disclosure(s): Nothing relevant to the subject of the presented research.
Dr. Michal Gniot
Contributions
Contributions
Abstract
Abstract: E1101
Type: Eposter Presentation
Background
Since 2012, the dynamics of early molecular response to tyrosine kinase inhibitor (TKI) treatment is being considered a very useful prognostic factor for further outcome of chronic myeloid leukemia (CML) patients. Two ways of determining dynamics of response are being used: BCR-ABL1 transcript level at 3rd month of the therapy and individual transcript reduction rate, expressed as BCR-ABL1 halving time (HT).
Aims
The goal of this analysis was to determine whether BCR-ABL1 transcript level at third month or BCR-ABL1 HT is more useful for predicting the molecular responses. Another aim was to perform the analysis using GUSb as a reference gene, which should provide more accurate results for high BCR-ABL1 transcript level samples.
Methods
The analyzed group consisted of 96 patients diagnosed with CML in Faculty of Hematology and Bone Marrow Transplantation at Poznań Medical University, who were monitored and treated according to ELN recommendations. The BCR-ABL1 transcript level assessment was performed using an in-house method with GUSb as a reference gene. The method is being validated on a regular basis in the reference laboratory in Adelaide, and in 2014 was positively validated for MR4.5 assesment (ELN/EUTOS performance evaluation). Statistical analysis was made using Statistica 10. All analyses were performed only in patients with full clinical documentation, non-degraded pre-treatment sample and at least 3 years of follow up. The Kaplan-Meier analyses of MMR, MR4 and MR4.5 were performed for groups divided by BCR-ABL1 halving values (5-40 days interval). The frequencies of molecular responses in 12th, 24th and 36th month of therapy were aggregated in tables and the graphs showing MMR, MR4 and MR4.5 in selected time points depending on HT cut-off values were plotted.
Results
The BCR-ABL1 transcript level at 3rd month was proven to have a limited prognostic value. The values greater than 10% and lower than 1% have significant prognostic implications; the interval between 1 and 10% (49% of our patients) does not predict any molecular outcome. On the other hand, the BCR-ABL1 HT of 15 days was proven to be a great predictor of MMR, MR4 and MR4.5. 91,5% of patients with HT shorter than 15 days achieved MMR by 12th month of treatment (100% by 24th and 36th month). In case of deep molecular responses, 61,1% achieved MR4 after a year of treatment (83,3% by 24th and 94,4% by 36th month) and 33,3% MR4.5 after twelve months of TKI therapy (80,5% by 24th and 83,7% by 36th month). The molecular outcome of patients with BCR-ABL1 HT greater than 15 days was significantly worse: 31,8%, 61,7% and 69,4% had MMR by 12th, 24th and 36th month of therapy, respectively. Moreover, the frequency of deep molecular responses was also significantly lower: 9,1%, 36,5% and 41,4% for MR4 and 4,5%, 16% and 28,8% for MR4.5, respectively.
Conclusion
Our results confirmed that the use of GUSb as a reference gene allows precise evaluation of transcript level at the beginning of the treatment and probably increases the prognostic value of BCR-ABL1 HT. The BCR-ABL1 HT below 15 days is an accurate predictor of molecular response for TKI treated CML patients. The response to the therapy is so good that the surrogate endpoint such as MMR is achieved by vast majority of them, regardless of the initial response dynamics. The BCR-ABL1 HT greater than 15 days also predicts significantly lower molecular response rates, especially MR4 and MR4.5. It is worth pointing out that the proposed BCR-ABL1 HT cut-off is applicable to the entire group of patients and allows for early identification of potential non-responders.
Session topic: E-poster
Keyword(s): BCR-ABL, Chronic myeloid leukemia, Molecular response, Prognostic factor
Type: Eposter Presentation
Background
Since 2012, the dynamics of early molecular response to tyrosine kinase inhibitor (TKI) treatment is being considered a very useful prognostic factor for further outcome of chronic myeloid leukemia (CML) patients. Two ways of determining dynamics of response are being used: BCR-ABL1 transcript level at 3rd month of the therapy and individual transcript reduction rate, expressed as BCR-ABL1 halving time (HT).
Aims
The goal of this analysis was to determine whether BCR-ABL1 transcript level at third month or BCR-ABL1 HT is more useful for predicting the molecular responses. Another aim was to perform the analysis using GUSb as a reference gene, which should provide more accurate results for high BCR-ABL1 transcript level samples.
Methods
The analyzed group consisted of 96 patients diagnosed with CML in Faculty of Hematology and Bone Marrow Transplantation at Poznań Medical University, who were monitored and treated according to ELN recommendations. The BCR-ABL1 transcript level assessment was performed using an in-house method with GUSb as a reference gene. The method is being validated on a regular basis in the reference laboratory in Adelaide, and in 2014 was positively validated for MR4.5 assesment (ELN/EUTOS performance evaluation). Statistical analysis was made using Statistica 10. All analyses were performed only in patients with full clinical documentation, non-degraded pre-treatment sample and at least 3 years of follow up. The Kaplan-Meier analyses of MMR, MR4 and MR4.5 were performed for groups divided by BCR-ABL1 halving values (5-40 days interval). The frequencies of molecular responses in 12th, 24th and 36th month of therapy were aggregated in tables and the graphs showing MMR, MR4 and MR4.5 in selected time points depending on HT cut-off values were plotted.
Results
The BCR-ABL1 transcript level at 3rd month was proven to have a limited prognostic value. The values greater than 10% and lower than 1% have significant prognostic implications; the interval between 1 and 10% (49% of our patients) does not predict any molecular outcome. On the other hand, the BCR-ABL1 HT of 15 days was proven to be a great predictor of MMR, MR4 and MR4.5. 91,5% of patients with HT shorter than 15 days achieved MMR by 12th month of treatment (100% by 24th and 36th month). In case of deep molecular responses, 61,1% achieved MR4 after a year of treatment (83,3% by 24th and 94,4% by 36th month) and 33,3% MR4.5 after twelve months of TKI therapy (80,5% by 24th and 83,7% by 36th month). The molecular outcome of patients with BCR-ABL1 HT greater than 15 days was significantly worse: 31,8%, 61,7% and 69,4% had MMR by 12th, 24th and 36th month of therapy, respectively. Moreover, the frequency of deep molecular responses was also significantly lower: 9,1%, 36,5% and 41,4% for MR4 and 4,5%, 16% and 28,8% for MR4.5, respectively.
Conclusion
Our results confirmed that the use of GUSb as a reference gene allows precise evaluation of transcript level at the beginning of the treatment and probably increases the prognostic value of BCR-ABL1 HT. The BCR-ABL1 HT below 15 days is an accurate predictor of molecular response for TKI treated CML patients. The response to the therapy is so good that the surrogate endpoint such as MMR is achieved by vast majority of them, regardless of the initial response dynamics. The BCR-ABL1 HT greater than 15 days also predicts significantly lower molecular response rates, especially MR4 and MR4.5. It is worth pointing out that the proposed BCR-ABL1 HT cut-off is applicable to the entire group of patients and allows for early identification of potential non-responders.
Session topic: E-poster
Keyword(s): BCR-ABL, Chronic myeloid leukemia, Molecular response, Prognostic factor
Abstract: E1101
Type: Eposter Presentation
Background
Since 2012, the dynamics of early molecular response to tyrosine kinase inhibitor (TKI) treatment is being considered a very useful prognostic factor for further outcome of chronic myeloid leukemia (CML) patients. Two ways of determining dynamics of response are being used: BCR-ABL1 transcript level at 3rd month of the therapy and individual transcript reduction rate, expressed as BCR-ABL1 halving time (HT).
Aims
The goal of this analysis was to determine whether BCR-ABL1 transcript level at third month or BCR-ABL1 HT is more useful for predicting the molecular responses. Another aim was to perform the analysis using GUSb as a reference gene, which should provide more accurate results for high BCR-ABL1 transcript level samples.
Methods
The analyzed group consisted of 96 patients diagnosed with CML in Faculty of Hematology and Bone Marrow Transplantation at Poznań Medical University, who were monitored and treated according to ELN recommendations. The BCR-ABL1 transcript level assessment was performed using an in-house method with GUSb as a reference gene. The method is being validated on a regular basis in the reference laboratory in Adelaide, and in 2014 was positively validated for MR4.5 assesment (ELN/EUTOS performance evaluation). Statistical analysis was made using Statistica 10. All analyses were performed only in patients with full clinical documentation, non-degraded pre-treatment sample and at least 3 years of follow up. The Kaplan-Meier analyses of MMR, MR4 and MR4.5 were performed for groups divided by BCR-ABL1 halving values (5-40 days interval). The frequencies of molecular responses in 12th, 24th and 36th month of therapy were aggregated in tables and the graphs showing MMR, MR4 and MR4.5 in selected time points depending on HT cut-off values were plotted.
Results
The BCR-ABL1 transcript level at 3rd month was proven to have a limited prognostic value. The values greater than 10% and lower than 1% have significant prognostic implications; the interval between 1 and 10% (49% of our patients) does not predict any molecular outcome. On the other hand, the BCR-ABL1 HT of 15 days was proven to be a great predictor of MMR, MR4 and MR4.5. 91,5% of patients with HT shorter than 15 days achieved MMR by 12th month of treatment (100% by 24th and 36th month). In case of deep molecular responses, 61,1% achieved MR4 after a year of treatment (83,3% by 24th and 94,4% by 36th month) and 33,3% MR4.5 after twelve months of TKI therapy (80,5% by 24th and 83,7% by 36th month). The molecular outcome of patients with BCR-ABL1 HT greater than 15 days was significantly worse: 31,8%, 61,7% and 69,4% had MMR by 12th, 24th and 36th month of therapy, respectively. Moreover, the frequency of deep molecular responses was also significantly lower: 9,1%, 36,5% and 41,4% for MR4 and 4,5%, 16% and 28,8% for MR4.5, respectively.
Conclusion
Our results confirmed that the use of GUSb as a reference gene allows precise evaluation of transcript level at the beginning of the treatment and probably increases the prognostic value of BCR-ABL1 HT. The BCR-ABL1 HT below 15 days is an accurate predictor of molecular response for TKI treated CML patients. The response to the therapy is so good that the surrogate endpoint such as MMR is achieved by vast majority of them, regardless of the initial response dynamics. The BCR-ABL1 HT greater than 15 days also predicts significantly lower molecular response rates, especially MR4 and MR4.5. It is worth pointing out that the proposed BCR-ABL1 HT cut-off is applicable to the entire group of patients and allows for early identification of potential non-responders.
Session topic: E-poster
Keyword(s): BCR-ABL, Chronic myeloid leukemia, Molecular response, Prognostic factor
Type: Eposter Presentation
Background
Since 2012, the dynamics of early molecular response to tyrosine kinase inhibitor (TKI) treatment is being considered a very useful prognostic factor for further outcome of chronic myeloid leukemia (CML) patients. Two ways of determining dynamics of response are being used: BCR-ABL1 transcript level at 3rd month of the therapy and individual transcript reduction rate, expressed as BCR-ABL1 halving time (HT).
Aims
The goal of this analysis was to determine whether BCR-ABL1 transcript level at third month or BCR-ABL1 HT is more useful for predicting the molecular responses. Another aim was to perform the analysis using GUSb as a reference gene, which should provide more accurate results for high BCR-ABL1 transcript level samples.
Methods
The analyzed group consisted of 96 patients diagnosed with CML in Faculty of Hematology and Bone Marrow Transplantation at Poznań Medical University, who were monitored and treated according to ELN recommendations. The BCR-ABL1 transcript level assessment was performed using an in-house method with GUSb as a reference gene. The method is being validated on a regular basis in the reference laboratory in Adelaide, and in 2014 was positively validated for MR4.5 assesment (ELN/EUTOS performance evaluation). Statistical analysis was made using Statistica 10. All analyses were performed only in patients with full clinical documentation, non-degraded pre-treatment sample and at least 3 years of follow up. The Kaplan-Meier analyses of MMR, MR4 and MR4.5 were performed for groups divided by BCR-ABL1 halving values (5-40 days interval). The frequencies of molecular responses in 12th, 24th and 36th month of therapy were aggregated in tables and the graphs showing MMR, MR4 and MR4.5 in selected time points depending on HT cut-off values were plotted.
Results
The BCR-ABL1 transcript level at 3rd month was proven to have a limited prognostic value. The values greater than 10% and lower than 1% have significant prognostic implications; the interval between 1 and 10% (49% of our patients) does not predict any molecular outcome. On the other hand, the BCR-ABL1 HT of 15 days was proven to be a great predictor of MMR, MR4 and MR4.5. 91,5% of patients with HT shorter than 15 days achieved MMR by 12th month of treatment (100% by 24th and 36th month). In case of deep molecular responses, 61,1% achieved MR4 after a year of treatment (83,3% by 24th and 94,4% by 36th month) and 33,3% MR4.5 after twelve months of TKI therapy (80,5% by 24th and 83,7% by 36th month). The molecular outcome of patients with BCR-ABL1 HT greater than 15 days was significantly worse: 31,8%, 61,7% and 69,4% had MMR by 12th, 24th and 36th month of therapy, respectively. Moreover, the frequency of deep molecular responses was also significantly lower: 9,1%, 36,5% and 41,4% for MR4 and 4,5%, 16% and 28,8% for MR4.5, respectively.
Conclusion
Our results confirmed that the use of GUSb as a reference gene allows precise evaluation of transcript level at the beginning of the treatment and probably increases the prognostic value of BCR-ABL1 HT. The BCR-ABL1 HT below 15 days is an accurate predictor of molecular response for TKI treated CML patients. The response to the therapy is so good that the surrogate endpoint such as MMR is achieved by vast majority of them, regardless of the initial response dynamics. The BCR-ABL1 HT greater than 15 days also predicts significantly lower molecular response rates, especially MR4 and MR4.5. It is worth pointing out that the proposed BCR-ABL1 HT cut-off is applicable to the entire group of patients and allows for early identification of potential non-responders.
Session topic: E-poster
Keyword(s): BCR-ABL, Chronic myeloid leukemia, Molecular response, Prognostic factor
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