Clinical impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML)
We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of pa...
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| Veröffentlicht in: | Leukemia 2021-05, Vol.35 (5), p.1392-1404 |
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| creator | Patkar, Nikhil Kakirde, Chinmayee Shaikh, Anam Fatima Salve, Rakhi Bhanshe, Prasanna Chatterjee, Gaurav Rajpal, Sweta Joshi, Swapnali Chaudhary, Shruti Kodgule, Rohan Ghoghale, Sitaram Deshpande, Nilesh Shetty, Dhanalaxmi Khizer, Syed Hasan Jain, Hasmukh Bagal, Bhausaheb Menon, Hari Khattry, Navin Sengar, Manju Tembhare, Prashant Subramanian, Papagudi Gujral, Sumeet |
| description | We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients were PI NGS-MRD
+
and 40.9% PC NGS-MRD
+
(median VAF 0.76%). NGS-MRD
+
patients had a significantly higher cumulative incidence of relapse (
p
= 0.003), inferior overall survival (
p
= 0.001) and relapse free survival (
p
|
| doi_str_mv | 10.1038/s41375-021-01131-6 |
| format | Article |
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+
and 40.9% PC NGS-MRD
+
(median VAF 0.76%). NGS-MRD
+
patients had a significantly higher cumulative incidence of relapse (
p
= 0.003), inferior overall survival (
p
= 0.001) and relapse free survival (
p
< 0.001) as compared to NGS-MRD
−
patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. PI NGS-MRD
−
patients had a significantly improved survival as compared to patients who became NGS-MRD
−
subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were NGS-MRD
−
but FCM-MRD
+
. NGS-MRD provided additional information of the risk of relapse when compared to FCM-MRD. We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and synergistic to FCM-MRD in AML treated with conventional therapies. Maximum clinical utility may be leveraged by combining FCM and NGS-MRD modalities.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-021-01131-6</identifier><identifier>PMID: 33558666</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 631/67/69 ; 692/308/575 ; Acute myeloid leukemia ; Adolescent ; Adult ; Cancer cells ; Cancer Research ; Comparative analysis ; Critical Care Medicine ; Cytogenetics ; Disease Progression ; DNA sequencing ; Error correction ; Female ; Flow cytometry ; Flow Cytometry - methods ; Genetic aspects ; Hematology ; Hematopoietic Stem Cell Transplantation - methods ; High-Throughput Nucleotide Sequencing - methods ; Humans ; Identification and classification ; Intensive ; Internal Medicine ; Leukemia ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - pathology ; Male ; Measurement ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutation - genetics ; Myeloid leukemia ; Neoplasm, Residual - diagnosis ; Neoplasm, Residual - genetics ; Neoplasm, Residual - pathology ; Next-generation sequencing ; Nucleotide sequencing ; Oncology ; Recurrence ; Remission ; Risk ; Sensitivity analysis ; Survival ; Young Adult</subject><ispartof>Leukemia, 2021-05, Vol.35 (5), p.1392-1404</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature 2021</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-875f5a492545c909ce205bfb3b4aff33aa10ab4c3318fd633594e41d8d302fc53</citedby><cites>FETCH-LOGICAL-c505t-875f5a492545c909ce205bfb3b4aff33aa10ab4c3318fd633594e41d8d302fc53</cites><orcidid>0000-0001-5708-6472 ; 0000-0001-9107-5937 ; 0000-0002-9030-0415 ; 0000-0001-9234-2857</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41375-021-01131-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-021-01131-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33558666$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Patkar, Nikhil</creatorcontrib><creatorcontrib>Kakirde, Chinmayee</creatorcontrib><creatorcontrib>Shaikh, Anam Fatima</creatorcontrib><creatorcontrib>Salve, Rakhi</creatorcontrib><creatorcontrib>Bhanshe, Prasanna</creatorcontrib><creatorcontrib>Chatterjee, Gaurav</creatorcontrib><creatorcontrib>Rajpal, Sweta</creatorcontrib><creatorcontrib>Joshi, Swapnali</creatorcontrib><creatorcontrib>Chaudhary, Shruti</creatorcontrib><creatorcontrib>Kodgule, Rohan</creatorcontrib><creatorcontrib>Ghoghale, Sitaram</creatorcontrib><creatorcontrib>Deshpande, Nilesh</creatorcontrib><creatorcontrib>Shetty, Dhanalaxmi</creatorcontrib><creatorcontrib>Khizer, Syed Hasan</creatorcontrib><creatorcontrib>Jain, Hasmukh</creatorcontrib><creatorcontrib>Bagal, Bhausaheb</creatorcontrib><creatorcontrib>Menon, Hari</creatorcontrib><creatorcontrib>Khattry, Navin</creatorcontrib><creatorcontrib>Sengar, Manju</creatorcontrib><creatorcontrib>Tembhare, Prashant</creatorcontrib><creatorcontrib>Subramanian, Papagudi</creatorcontrib><creatorcontrib>Gujral, Sumeet</creatorcontrib><title>Clinical impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML)</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients were PI NGS-MRD
+
and 40.9% PC NGS-MRD
+
(median VAF 0.76%). NGS-MRD
+
patients had a significantly higher cumulative incidence of relapse (
p
= 0.003), inferior overall survival (
p
= 0.001) and relapse free survival (
p
< 0.001) as compared to NGS-MRD
−
patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. PI NGS-MRD
−
patients had a significantly improved survival as compared to patients who became NGS-MRD
−
subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were NGS-MRD
−
but FCM-MRD
+
. NGS-MRD provided additional information of the risk of relapse when compared to FCM-MRD. We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and synergistic to FCM-MRD in AML treated with conventional therapies. Maximum clinical utility may be leveraged by combining FCM and NGS-MRD modalities.</description><subject>45</subject><subject>631/67/69</subject><subject>692/308/575</subject><subject>Acute myeloid leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Cancer cells</subject><subject>Cancer Research</subject><subject>Comparative analysis</subject><subject>Critical Care Medicine</subject><subject>Cytogenetics</subject><subject>Disease Progression</subject><subject>DNA sequencing</subject><subject>Error correction</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Flow Cytometry - methods</subject><subject>Genetic aspects</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Male</subject><subject>Measurement</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Myeloid leukemia</subject><subject>Neoplasm, Residual - diagnosis</subject><subject>Neoplasm, Residual - genetics</subject><subject>Neoplasm, Residual - pathology</subject><subject>Next-generation sequencing</subject><subject>Nucleotide sequencing</subject><subject>Oncology</subject><subject>Recurrence</subject><subject>Remission</subject><subject>Risk</subject><subject>Sensitivity analysis</subject><subject>Survival</subject><subject>Young 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impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML)</title><author>Patkar, Nikhil ; Kakirde, Chinmayee ; Shaikh, Anam Fatima ; Salve, Rakhi ; Bhanshe, Prasanna ; Chatterjee, Gaurav ; Rajpal, Sweta ; Joshi, Swapnali ; Chaudhary, Shruti ; Kodgule, Rohan ; Ghoghale, Sitaram ; Deshpande, Nilesh ; Shetty, Dhanalaxmi ; Khizer, Syed Hasan ; Jain, Hasmukh ; Bagal, Bhausaheb ; Menon, Hari ; Khattry, Navin ; Sengar, Manju ; Tembhare, Prashant ; Subramanian, Papagudi ; Gujral, Sumeet</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-875f5a492545c909ce205bfb3b4aff33aa10ab4c3318fd633594e41d8d302fc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>45</topic><topic>631/67/69</topic><topic>692/308/575</topic><topic>Acute myeloid 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genetics</topic><topic>Myeloid leukemia</topic><topic>Neoplasm, Residual - diagnosis</topic><topic>Neoplasm, Residual - genetics</topic><topic>Neoplasm, Residual - pathology</topic><topic>Next-generation sequencing</topic><topic>Nucleotide sequencing</topic><topic>Oncology</topic><topic>Recurrence</topic><topic>Remission</topic><topic>Risk</topic><topic>Sensitivity analysis</topic><topic>Survival</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Patkar, Nikhil</creatorcontrib><creatorcontrib>Kakirde, Chinmayee</creatorcontrib><creatorcontrib>Shaikh, Anam Fatima</creatorcontrib><creatorcontrib>Salve, Rakhi</creatorcontrib><creatorcontrib>Bhanshe, Prasanna</creatorcontrib><creatorcontrib>Chatterjee, Gaurav</creatorcontrib><creatorcontrib>Rajpal, Sweta</creatorcontrib><creatorcontrib>Joshi, Swapnali</creatorcontrib><creatorcontrib>Chaudhary, Shruti</creatorcontrib><creatorcontrib>Kodgule, 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Fatima</au><au>Salve, Rakhi</au><au>Bhanshe, Prasanna</au><au>Chatterjee, Gaurav</au><au>Rajpal, Sweta</au><au>Joshi, Swapnali</au><au>Chaudhary, Shruti</au><au>Kodgule, Rohan</au><au>Ghoghale, Sitaram</au><au>Deshpande, Nilesh</au><au>Shetty, Dhanalaxmi</au><au>Khizer, Syed Hasan</au><au>Jain, Hasmukh</au><au>Bagal, Bhausaheb</au><au>Menon, Hari</au><au>Khattry, Navin</au><au>Sengar, Manju</au><au>Tembhare, Prashant</au><au>Subramanian, Papagudi</au><au>Gujral, Sumeet</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML)</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2021-05-01</date><risdate>2021</risdate><volume>35</volume><issue>5</issue><spage>1392</spage><epage>1404</epage><pages>1392-1404</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients were PI NGS-MRD
+
and 40.9% PC NGS-MRD
+
(median VAF 0.76%). NGS-MRD
+
patients had a significantly higher cumulative incidence of relapse (
p
= 0.003), inferior overall survival (
p
= 0.001) and relapse free survival (
p
< 0.001) as compared to NGS-MRD
−
patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. PI NGS-MRD
−
patients had a significantly improved survival as compared to patients who became NGS-MRD
−
subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were NGS-MRD
−
but FCM-MRD
+
. NGS-MRD provided additional information of the risk of relapse when compared to FCM-MRD. We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and synergistic to FCM-MRD in AML treated with conventional therapies. Maximum clinical utility may be leveraged by combining FCM and NGS-MRD modalities.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33558666</pmid><doi>10.1038/s41375-021-01131-6</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-5708-6472</orcidid><orcidid>https://orcid.org/0000-0001-9107-5937</orcidid><orcidid>https://orcid.org/0000-0002-9030-0415</orcidid><orcidid>https://orcid.org/0000-0001-9234-2857</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2021-05, Vol.35 (5), p.1392-1404 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8102181 |
| source | MEDLINE; SpringerLink Journals |
| subjects | 45 631/67/69 692/308/575 Acute myeloid leukemia Adolescent Adult Cancer cells Cancer Research Comparative analysis Critical Care Medicine Cytogenetics Disease Progression DNA sequencing Error correction Female Flow cytometry Flow Cytometry - methods Genetic aspects Hematology Hematopoietic Stem Cell Transplantation - methods High-Throughput Nucleotide Sequencing - methods Humans Identification and classification Intensive Internal Medicine Leukemia Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - pathology Male Measurement Medicine Medicine & Public Health Middle Aged Mutation - genetics Myeloid leukemia Neoplasm, Residual - diagnosis Neoplasm, Residual - genetics Neoplasm, Residual - pathology Next-generation sequencing Nucleotide sequencing Oncology Recurrence Remission Risk Sensitivity analysis Survival Young Adult |
| title | Clinical impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T05%3A08%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clinical%20impact%20of%20panel-based%20error-corrected%20next%20generation%20sequencing%20versus%20flow%20cytometry%20to%20detect%20measurable%20residual%20disease%20(MRD)%20in%20acute%20myeloid%20leukemia%20(AML)&rft.jtitle=Leukemia&rft.au=Patkar,%20Nikhil&rft.date=2021-05-01&rft.volume=35&rft.issue=5&rft.spage=1392&rft.epage=1404&rft.pages=1392-1404&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/s41375-021-01131-6&rft_dat=%3Cgale_pubme%3EA660954825%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2522497962&rft_id=info:pmid/33558666&rft_galeid=A660954825&rfr_iscdi=true |