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Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context

Introduction: One of the mainstays of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR). However, not all patients by this remission criterion achieve long-term remission and a subset relapse. This relapse is explained by the prese...

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Autores principales: Patkar, Nikhil, Kakirde, Chinmayee, Bhanshe, Prasanna, Joshi, Swapnali, Chaudhary, Shruti, Badrinath, Yajamanam, Ghoghale, Sitaram, Deshpande, Nilesh, Kadechkar, Shraddha, Chatterjee, Gaurav, Kannan, Sadhana, Shetty, Dhanalaxmi, Gokarn, Anant, Punatkar, Sachin, Bonda, Avinash, Nayak, Lingaraj, Jain, Hasmukh, Bagal, Bhausaheb, Menon, Hari, Sengar, Manju, Khizer, Syed Hasan, Khattry, Navin, Tembhare, Prashant, Gujral, Sumeet, Subramanian, Papagudi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584962/
https://www.ncbi.nlm.nih.gov/pubmed/31263671
http://dx.doi.org/10.3389/fonc.2019.00450
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author Patkar, Nikhil
Kakirde, Chinmayee
Bhanshe, Prasanna
Joshi, Swapnali
Chaudhary, Shruti
Badrinath, Yajamanam
Ghoghale, Sitaram
Deshpande, Nilesh
Kadechkar, Shraddha
Chatterjee, Gaurav
Kannan, Sadhana
Shetty, Dhanalaxmi
Gokarn, Anant
Punatkar, Sachin
Bonda, Avinash
Nayak, Lingaraj
Jain, Hasmukh
Bagal, Bhausaheb
Menon, Hari
Sengar, Manju
Khizer, Syed Hasan
Khattry, Navin
Tembhare, Prashant
Gujral, Sumeet
Subramanian, Papagudi
author_facet Patkar, Nikhil
Kakirde, Chinmayee
Bhanshe, Prasanna
Joshi, Swapnali
Chaudhary, Shruti
Badrinath, Yajamanam
Ghoghale, Sitaram
Deshpande, Nilesh
Kadechkar, Shraddha
Chatterjee, Gaurav
Kannan, Sadhana
Shetty, Dhanalaxmi
Gokarn, Anant
Punatkar, Sachin
Bonda, Avinash
Nayak, Lingaraj
Jain, Hasmukh
Bagal, Bhausaheb
Menon, Hari
Sengar, Manju
Khizer, Syed Hasan
Khattry, Navin
Tembhare, Prashant
Gujral, Sumeet
Subramanian, Papagudi
author_sort Patkar, Nikhil
collection PubMed
description Introduction: One of the mainstays of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR). However, not all patients by this remission criterion achieve long-term remission and a subset relapse. This relapse is explained by the presence of measurable residual disease (MRD). Methods: We accrued 451 consecutive patients of adult AML (from March 2012 to December 2017) after informed consent. All patients received standard chemotherapy. MRD testing was done at post-induction and, if feasible, post-consolidation using 8- and later 10-color FCM. Analysis of MRD was done using a combination of difference from normal and leukemia-associated immunophenotype approaches. Conventional karyotyping and FISH were done as per standard recommendations, and patients were classified into favorable, intermediate, and poor cytogenetic risk groups. The presence of FLT3-ITD, NPM1, and CEBPA mutations was detected by a fragment length analysis-based assay. Results: As compared to Western data, our cohort of patients was younger with a median age of 35 years. There were 62 induction deaths in this cohort (13.7%), and 77 patients (17.1%) were not in morphological remission. The median follow-up was 26.0 months. Poor-risk cytogenetics and the presence of FLT3-ITD were significantly associated with inferior outcome. The presence of post-induction MRD assessment was significantly associated with adverse outcome with respect to OS (p = 0.01) as well as RFS (p = 0.004). Among established genetic subgroups, detection of MRD in intermediate cytogenetic and NPM1 mutated groups was also highly predictive of inferior outcome. On multivariate analysis, immunophenotypic MRD at the end of induction and FLT3-ITD emerged as independent prognostic factors predictive for outcome. Conclusion: This is the first data from a resource-constrained real-world setting demonstrating the utility of AML MRD as well as long-term outcome of AML. Our data is in agreement with other studies that determination of MRD is extremely important in predicting outcome. AML MRD is a very useful guide for guiding post-remission strategies in AML and should be incorporated into routine treatment algorithms.
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spelling pubmed-65849622019-07-01 Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context Patkar, Nikhil Kakirde, Chinmayee Bhanshe, Prasanna Joshi, Swapnali Chaudhary, Shruti Badrinath, Yajamanam Ghoghale, Sitaram Deshpande, Nilesh Kadechkar, Shraddha Chatterjee, Gaurav Kannan, Sadhana Shetty, Dhanalaxmi Gokarn, Anant Punatkar, Sachin Bonda, Avinash Nayak, Lingaraj Jain, Hasmukh Bagal, Bhausaheb Menon, Hari Sengar, Manju Khizer, Syed Hasan Khattry, Navin Tembhare, Prashant Gujral, Sumeet Subramanian, Papagudi Front Oncol Oncology Introduction: One of the mainstays of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR). However, not all patients by this remission criterion achieve long-term remission and a subset relapse. This relapse is explained by the presence of measurable residual disease (MRD). Methods: We accrued 451 consecutive patients of adult AML (from March 2012 to December 2017) after informed consent. All patients received standard chemotherapy. MRD testing was done at post-induction and, if feasible, post-consolidation using 8- and later 10-color FCM. Analysis of MRD was done using a combination of difference from normal and leukemia-associated immunophenotype approaches. Conventional karyotyping and FISH were done as per standard recommendations, and patients were classified into favorable, intermediate, and poor cytogenetic risk groups. The presence of FLT3-ITD, NPM1, and CEBPA mutations was detected by a fragment length analysis-based assay. Results: As compared to Western data, our cohort of patients was younger with a median age of 35 years. There were 62 induction deaths in this cohort (13.7%), and 77 patients (17.1%) were not in morphological remission. The median follow-up was 26.0 months. Poor-risk cytogenetics and the presence of FLT3-ITD were significantly associated with inferior outcome. The presence of post-induction MRD assessment was significantly associated with adverse outcome with respect to OS (p = 0.01) as well as RFS (p = 0.004). Among established genetic subgroups, detection of MRD in intermediate cytogenetic and NPM1 mutated groups was also highly predictive of inferior outcome. On multivariate analysis, immunophenotypic MRD at the end of induction and FLT3-ITD emerged as independent prognostic factors predictive for outcome. Conclusion: This is the first data from a resource-constrained real-world setting demonstrating the utility of AML MRD as well as long-term outcome of AML. Our data is in agreement with other studies that determination of MRD is extremely important in predicting outcome. AML MRD is a very useful guide for guiding post-remission strategies in AML and should be incorporated into routine treatment algorithms. Frontiers Media S.A. 2019-06-13 /pmc/articles/PMC6584962/ /pubmed/31263671 http://dx.doi.org/10.3389/fonc.2019.00450 Text en Copyright © 2019 Patkar, Kakirde, Bhanshe, Joshi, Chaudhary, Badrinath, Ghoghale, Deshpande, Kadechkar, Chatterjee, Kannan, Shetty, Gokarn, Punatkar, Bonda, Nayak, Jain, Bagal, Menon, Sengar, Khizer, Khattry, Tembhare, Gujral and Subramanian. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Patkar, Nikhil
Kakirde, Chinmayee
Bhanshe, Prasanna
Joshi, Swapnali
Chaudhary, Shruti
Badrinath, Yajamanam
Ghoghale, Sitaram
Deshpande, Nilesh
Kadechkar, Shraddha
Chatterjee, Gaurav
Kannan, Sadhana
Shetty, Dhanalaxmi
Gokarn, Anant
Punatkar, Sachin
Bonda, Avinash
Nayak, Lingaraj
Jain, Hasmukh
Bagal, Bhausaheb
Menon, Hari
Sengar, Manju
Khizer, Syed Hasan
Khattry, Navin
Tembhare, Prashant
Gujral, Sumeet
Subramanian, Papagudi
Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context
title Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context
title_full Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context
title_fullStr Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context
title_full_unstemmed Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context
title_short Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia—Real-World Context
title_sort utility of immunophenotypic measurable residual disease in adult acute myeloid leukemia—real-world context
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584962/
https://www.ncbi.nlm.nih.gov/pubmed/31263671
http://dx.doi.org/10.3389/fonc.2019.00450
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