Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction

Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-...

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Veröffentlicht in:PloS one 2013-07, Vol.8 (7), p.e69467-e69467
Hauptverfasser: Cheng, Suk Hang, Lau, Kin Mang, Li, Chi Kong, Chan, Natalie P H, Ip, Rosalina K L, Cheng, Chi Keung, Lee, Vincent, Shing, Matthew M K, Leung, Alex W K, Ha, Shau Yin, Cheuk, Daniel K L, Lee, Anselm C W, Li, Chak Ho, Luk, Chung Wing, Ling, Siu Cheung, Hrusak, Ondrej, Mejstrikova, Ester, Leung, Yonna, Ng, Margaret H L
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container_issue 7
container_start_page e69467
container_title PloS one
container_volume 8
creator Cheng, Suk Hang
Lau, Kin Mang
Li, Chi Kong
Chan, Natalie P H
Ip, Rosalina K L
Cheng, Chi Keung
Lee, Vincent
Shing, Matthew M K
Leung, Alex W K
Ha, Shau Yin
Cheuk, Daniel K L
Lee, Anselm C W
Li, Chak Ho
Luk, Chung Wing
Ling, Siu Cheung
Hrusak, Ondrej
Mejstrikova, Ester
Leung, Yonna
Ng, Margaret H L
description Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: 10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15
doi_str_mv 10.1371/journal.pone.0069467
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In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: &lt;0.1%, I-B: 0.1-10%, I-C: &gt;10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15&lt;10% and day-33&lt;0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and &lt;0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069467</identifier><identifier>PMID: 23936021</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Adolescent ; Antigens ; Antineoplastic Agents - administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols ; Biology ; Blood ; Blood plasma ; Bone marrow ; Cancer genetics ; Cancer research ; Cancer therapies ; Child ; Child, Preschool ; Childhood ; Children ; Cytometry ; Deoxyribonucleic acid ; Disease-Free Survival ; DNA ; DNA, Neoplasm - genetics ; Female ; Flow Cytometry ; Gating ; Health risks ; Hematology ; Humans ; Infant ; Invasiveness ; Leukemia ; Lymphatic leukemia ; Male ; Mathematical models ; Medical prognosis ; Medicine ; Minimal residual disease ; Monitoring ; Multivariate analysis ; Neoplasm, Residual ; Oncogene Proteins, Fusion - genetics ; Oncology ; Pathology ; Patients ; Pediatrics ; Peripheral blood ; Plasma ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Predictions ; Prognosis ; Quantitation ; Recurrence ; Risk ; Risk factors ; Risk groups ; Stem cell transplantation</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69467-e69467</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Cheng et al 2013 Cheng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ab026057192747e07043c8996acb38287ce3d50908db816cdf3b10709658ffca3</citedby><cites>FETCH-LOGICAL-c692t-ab026057192747e07043c8996acb38287ce3d50908db816cdf3b10709658ffca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723913/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723913/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23936021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Suk Hang</creatorcontrib><creatorcontrib>Lau, Kin Mang</creatorcontrib><creatorcontrib>Li, Chi Kong</creatorcontrib><creatorcontrib>Chan, Natalie P H</creatorcontrib><creatorcontrib>Ip, Rosalina K L</creatorcontrib><creatorcontrib>Cheng, Chi Keung</creatorcontrib><creatorcontrib>Lee, Vincent</creatorcontrib><creatorcontrib>Shing, Matthew M K</creatorcontrib><creatorcontrib>Leung, Alex W K</creatorcontrib><creatorcontrib>Ha, Shau Yin</creatorcontrib><creatorcontrib>Cheuk, Daniel K L</creatorcontrib><creatorcontrib>Lee, Anselm C W</creatorcontrib><creatorcontrib>Li, Chak Ho</creatorcontrib><creatorcontrib>Luk, Chung Wing</creatorcontrib><creatorcontrib>Ling, Siu Cheung</creatorcontrib><creatorcontrib>Hrusak, Ondrej</creatorcontrib><creatorcontrib>Mejstrikova, Ester</creatorcontrib><creatorcontrib>Leung, Yonna</creatorcontrib><creatorcontrib>Ng, Margaret H L</creatorcontrib><title>Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: &lt;0.1%, I-B: 0.1-10%, I-C: &gt;10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15&lt;10% and day-33&lt;0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and &lt;0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.</description><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Adolescent</subject><subject>Antigens</subject><subject>Antineoplastic Agents - administration &amp; dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols</subject><subject>Biology</subject><subject>Blood</subject><subject>Blood plasma</subject><subject>Bone marrow</subject><subject>Cancer genetics</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Childhood</subject><subject>Children</subject><subject>Cytometry</subject><subject>Deoxyribonucleic acid</subject><subject>Disease-Free Survival</subject><subject>DNA</subject><subject>DNA, Neoplasm - genetics</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Gating</subject><subject>Health risks</subject><subject>Hematology</subject><subject>Humans</subject><subject>Infant</subject><subject>Invasiveness</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Male</subject><subject>Mathematical models</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Minimal residual disease</subject><subject>Monitoring</subject><subject>Multivariate analysis</subject><subject>Neoplasm, Residual</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Peripheral blood</subject><subject>Plasma</subject><subject>Polymerase Chain Reaction</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Predictions</subject><subject>Prognosis</subject><subject>Quantitation</subject><subject>Recurrence</subject><subject>Risk</subject><subject>Risk factors</subject><subject>Risk groups</subject><subject>Stem cell 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residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction</title><author>Cheng, Suk Hang ; Lau, Kin Mang ; Li, Chi Kong ; Chan, Natalie P H ; Ip, Rosalina K L ; Cheng, Chi Keung ; Lee, Vincent ; Shing, Matthew M K ; Leung, Alex W K ; Ha, Shau Yin ; Cheuk, Daniel K L ; Lee, Anselm C W ; Li, Chak Ho ; Luk, Chung Wing ; Ling, Siu Cheung ; Hrusak, Ondrej ; Mejstrikova, Ester ; Leung, Yonna ; Ng, Margaret H L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ab026057192747e07043c8996acb38287ce3d50908db816cdf3b10709658ffca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Acute lymphocytic leukemia</topic><topic>Adolescent</topic><topic>Antigens</topic><topic>Antineoplastic Agents - administration &amp; dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols</topic><topic>Biology</topic><topic>Blood</topic><topic>Blood plasma</topic><topic>Bone marrow</topic><topic>Cancer genetics</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Childhood</topic><topic>Children</topic><topic>Cytometry</topic><topic>Deoxyribonucleic acid</topic><topic>Disease-Free Survival</topic><topic>DNA</topic><topic>DNA, Neoplasm - genetics</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Gating</topic><topic>Health risks</topic><topic>Hematology</topic><topic>Humans</topic><topic>Infant</topic><topic>Invasiveness</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Male</topic><topic>Mathematical models</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Minimal residual disease</topic><topic>Monitoring</topic><topic>Multivariate analysis</topic><topic>Neoplasm, 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Database</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied &amp; Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Suk Hang</au><au>Lau, Kin Mang</au><au>Li, Chi Kong</au><au>Chan, Natalie P H</au><au>Ip, Rosalina K L</au><au>Cheng, Chi Keung</au><au>Lee, Vincent</au><au>Shing, Matthew M K</au><au>Leung, Alex W K</au><au>Ha, Shau Yin</au><au>Cheuk, Daniel K L</au><au>Lee, Anselm C W</au><au>Li, Chak Ho</au><au>Luk, Chung Wing</au><au>Ling, Siu Cheung</au><au>Hrusak, Ondrej</au><au>Mejstrikova, Ester</au><au>Leung, Yonna</au><au>Ng, Margaret H L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-25</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e69467</spage><epage>e69467</epage><pages>e69467-e69467</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: &lt;0.1%, I-B: 0.1-10%, I-C: &gt;10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15&lt;10% and day-33&lt;0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and &lt;0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23936021</pmid><doi>10.1371/journal.pone.0069467</doi><tpages>e69467</tpages><oa>free_for_read</oa></addata></record>
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subjects Acute lymphoblastic leukemia
Acute lymphocytic leukemia
Adolescent
Antigens
Antineoplastic Agents - administration & dosage
Antineoplastic Combined Chemotherapy Protocols
Biology
Blood
Blood plasma
Bone marrow
Cancer genetics
Cancer research
Cancer therapies
Child
Child, Preschool
Childhood
Children
Cytometry
Deoxyribonucleic acid
Disease-Free Survival
DNA
DNA, Neoplasm - genetics
Female
Flow Cytometry
Gating
Health risks
Hematology
Humans
Infant
Invasiveness
Leukemia
Lymphatic leukemia
Male
Mathematical models
Medical prognosis
Medicine
Minimal residual disease
Monitoring
Multivariate analysis
Neoplasm, Residual
Oncogene Proteins, Fusion - genetics
Oncology
Pathology
Patients
Pediatrics
Peripheral blood
Plasma
Polymerase Chain Reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality
Predictions
Prognosis
Quantitation
Recurrence
Risk
Risk factors
Risk groups
Stem cell transplantation
title Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction
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