The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases

IntroductionMinimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilu...

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Main Authors: Ilaria Vigliotta, Silvia Armuzzi, Martina Barone, Vincenza Solli, Ignazia Pistis, Enrica Borsi, Barbara Taurisano, Gaia Mazzocchetti, Marina Martello, Andrea Poletti, Chiara Sartor, Ilaria Rizzello, Lucia Pantani, Paola Tacchetti, Cristina Papayannidis, Katia Mancuso, Serena Rocchi, Elena Zamagni, Antonio Curti, Mario Arpinati, Michele Cavo, Carolina Terragna
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1001048/full
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author Ilaria Vigliotta
Ilaria Vigliotta
Silvia Armuzzi
Silvia Armuzzi
Martina Barone
Martina Barone
Vincenza Solli
Vincenza Solli
Ignazia Pistis
Enrica Borsi
Enrica Borsi
Barbara Taurisano
Barbara Taurisano
Gaia Mazzocchetti
Gaia Mazzocchetti
Marina Martello
Marina Martello
Andrea Poletti
Andrea Poletti
Chiara Sartor
Chiara Sartor
Ilaria Rizzello
Ilaria Rizzello
Lucia Pantani
Paola Tacchetti
Cristina Papayannidis
Katia Mancuso
Katia Mancuso
Serena Rocchi
Serena Rocchi
Elena Zamagni
Elena Zamagni
Antonio Curti
Antonio Curti
Mario Arpinati
Mario Arpinati
Michele Cavo
Michele Cavo
Carolina Terragna
author_facet Ilaria Vigliotta
Ilaria Vigliotta
Silvia Armuzzi
Silvia Armuzzi
Martina Barone
Martina Barone
Vincenza Solli
Vincenza Solli
Ignazia Pistis
Enrica Borsi
Enrica Borsi
Barbara Taurisano
Barbara Taurisano
Gaia Mazzocchetti
Gaia Mazzocchetti
Marina Martello
Marina Martello
Andrea Poletti
Andrea Poletti
Chiara Sartor
Chiara Sartor
Ilaria Rizzello
Ilaria Rizzello
Lucia Pantani
Paola Tacchetti
Cristina Papayannidis
Katia Mancuso
Katia Mancuso
Serena Rocchi
Serena Rocchi
Elena Zamagni
Elena Zamagni
Antonio Curti
Antonio Curti
Mario Arpinati
Mario Arpinati
Michele Cavo
Michele Cavo
Carolina Terragna
author_sort Ilaria Vigliotta
collection DOAJ
description IntroductionMinimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilution, several flow cytometry (FC) strategies for hemodilution evaluation have been compared.MethodsFor each BM sample, cells populations with a well-known distribution in BM and peripheral blood - e.g., mast cells (MC), immature (IG) and mature granulocytes (N) – have been studied by FC and quantified alongside the BM differential count.ResultsThe frequencies of cells’ populations were correlated to the IG/N ratio, highlighting a mild correlation with MCs and erythroblasts (R=0.25 and R=0.38 respectively, with p-value=0.0006 and 0.0000052), whereas no significant correlation was found with B or T-cells. The mild correlation between IG/N, erythroblasts and MCs supported the combined use of these parameters to evaluate BM hemodilution, hence the optimization of the ALLgorithMM. Once validated, the ALLgorithMM was employed to evaluate the dilution status of BM samples in the context of MRD assessment. Overall, we found that 32% of FC and 52% of Next Generation Sequencing (NGS) analyses were MRD negative in samples resulted hemodiluted (HD) or at least mildly hemodiluted (mHD).ConclusionsThe high frequency of MRD-negative results in both HD and mHD samples implies the presence of possible false negative MRD measurements, impairing the correct assessment of patients’ response to therapy and highlighs the importance to evaluate BM hemodilution.
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spelling doaj.art-45f876f6faa8455682afb6ec6aa42bb92022-12-22T04:29:29ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10010481001048The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseasesIlaria Vigliotta0Ilaria Vigliotta1Silvia Armuzzi2Silvia Armuzzi3Martina Barone4Martina Barone5Vincenza Solli6Vincenza Solli7Ignazia Pistis8Enrica Borsi9Enrica Borsi10Barbara Taurisano11Barbara Taurisano12Gaia Mazzocchetti13Gaia Mazzocchetti14Marina Martello15Marina Martello16Andrea Poletti17Andrea Poletti18Chiara Sartor19Chiara Sartor20Ilaria Rizzello21Ilaria Rizzello22Lucia Pantani23Paola Tacchetti24Cristina Papayannidis25Katia Mancuso26Katia Mancuso27Serena Rocchi28Serena Rocchi29Elena Zamagni30Elena Zamagni31Antonio Curti32Antonio Curti33Mario Arpinati34Mario Arpinati35Michele Cavo36Michele Cavo37Carolina Terragna38IRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine - University of Bologna, Bologna, ItalyIRCCS Azienda Ospedaliero-Universitaria di Bologna, Seràgnoli Institute of Hematology, Bologna, ItalyIntroductionMinimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilution, several flow cytometry (FC) strategies for hemodilution evaluation have been compared.MethodsFor each BM sample, cells populations with a well-known distribution in BM and peripheral blood - e.g., mast cells (MC), immature (IG) and mature granulocytes (N) – have been studied by FC and quantified alongside the BM differential count.ResultsThe frequencies of cells’ populations were correlated to the IG/N ratio, highlighting a mild correlation with MCs and erythroblasts (R=0.25 and R=0.38 respectively, with p-value=0.0006 and 0.0000052), whereas no significant correlation was found with B or T-cells. The mild correlation between IG/N, erythroblasts and MCs supported the combined use of these parameters to evaluate BM hemodilution, hence the optimization of the ALLgorithMM. Once validated, the ALLgorithMM was employed to evaluate the dilution status of BM samples in the context of MRD assessment. Overall, we found that 32% of FC and 52% of Next Generation Sequencing (NGS) analyses were MRD negative in samples resulted hemodiluted (HD) or at least mildly hemodiluted (mHD).ConclusionsThe high frequency of MRD-negative results in both HD and mHD samples implies the presence of possible false negative MRD measurements, impairing the correct assessment of patients’ response to therapy and highlighs the importance to evaluate BM hemodilution.https://www.frontiersin.org/articles/10.3389/fonc.2022.1001048/fullminimal residual diseasemultiple myelomaacute lymphoblastic leukemiahemodilutionhemodilution/methodsflow cytometry
spellingShingle Ilaria Vigliotta
Ilaria Vigliotta
Silvia Armuzzi
Silvia Armuzzi
Martina Barone
Martina Barone
Vincenza Solli
Vincenza Solli
Ignazia Pistis
Enrica Borsi
Enrica Borsi
Barbara Taurisano
Barbara Taurisano
Gaia Mazzocchetti
Gaia Mazzocchetti
Marina Martello
Marina Martello
Andrea Poletti
Andrea Poletti
Chiara Sartor
Chiara Sartor
Ilaria Rizzello
Ilaria Rizzello
Lucia Pantani
Paola Tacchetti
Cristina Papayannidis
Katia Mancuso
Katia Mancuso
Serena Rocchi
Serena Rocchi
Elena Zamagni
Elena Zamagni
Antonio Curti
Antonio Curti
Mario Arpinati
Mario Arpinati
Michele Cavo
Michele Cavo
Carolina Terragna
The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases
Frontiers in Oncology
minimal residual disease
multiple myeloma
acute lymphoblastic leukemia
hemodilution
hemodilution/methods
flow cytometry
title The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases
title_full The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases
title_fullStr The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases
title_full_unstemmed The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases
title_short The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases
title_sort allgorithmm how to define the hemodilution of bone marrow samples in lymphoproliferative diseases
topic minimal residual disease
multiple myeloma
acute lymphoblastic leukemia
hemodilution
hemodilution/methods
flow cytometry
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1001048/full
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