Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?

Minimal residual disease (MRD) assessment plays a central role in risk stratification and treatment guidance in paediatric patients with acute lymphoblastic leukaemia (ALL). As such, MRD prior to haematopoietic stem cell transplantation (HSCT) is a major factor that is independently correlated with...

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Autores principales:	Pietro Merli, Marianne Ifversen, Tony H. Truong, Hanne V. Marquart, Jochen Buechner, Matthias Wölfl, Peter Bader
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	minimal residual disease (MRD) acute lymphoblastic leukaemia (ALL) haematopoietic stem cell transplantation (HSCT) children relapse Pediatrics RJ1-570
Acceso en línea:	https://doaj.org/article/e0a0937ef4b44e059d9150d003ca4ae9
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spelling	oai:doaj.org-article:e0a0937ef4b44e059d9150d003ca4ae92021-11-05T10:50:11ZMinimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?2296-236010.3389/fped.2021.777108https://doaj.org/article/e0a0937ef4b44e059d9150d003ca4ae92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fped.2021.777108/fullhttps://doaj.org/toc/2296-2360Minimal residual disease (MRD) assessment plays a central role in risk stratification and treatment guidance in paediatric patients with acute lymphoblastic leukaemia (ALL). As such, MRD prior to haematopoietic stem cell transplantation (HSCT) is a major factor that is independently correlated with outcome. High burden of MRD is negatively correlated with post-transplant survival, as both the risk of leukaemia recurrence and non-relapse mortality increase with greater levels of MRD. Despite growing evidence supporting these findings, controversies still exist. In particular, it is still not clear whether multiparameter flow cytometry and real-time quantitative polymerase chain reaction, which is used to recognise immunoglobulin and T-cell receptor gene rearrangements, can be employed interchangeably. Moreover, the higher sensitivity in MRD quantification offered by next-generation sequencing techniques may further refine the ability to stratify transplant-associated risks. While MRD quantification from bone marrow prior to HSCT remains the state of the art, heavily pre-treated patients may benefit from additional staging, such as using 18F-fluorodeoxyglucose positron emission tomography/computed tomography to detect focal residues of disease. Additionally, the timing of MRD detection (i.e., immediately before administration of the conditioning regimen or weeks before) is a matter of debate. Pre-transplant MRD negativity has previously been associated with superior outcomes; however, in the recent For Omitting Radiation Under Majority age (FORUM) study, pre-HSCT MRD positivity was associated with neither relapse risk nor survival. In this review, we discuss the level of MRD that may require pre-transplant therapy intensification, risking time delay and complications (as well as losing the window for HSCT if disease progression occurs), as opposed to an adapted post-transplant strategy to achieve long-term remission. Indeed, MRD monitoring may be a valuable tool to guide individualised treatment decisions, including tapering of immunosuppression, cellular therapies (such as donor lymphocyte infusions) or additional immunotherapy (such as bispecific T-cell engagers or chimeric antigen receptor T-cell therapy).Pietro MerliMarianne IfversenTony H. TruongHanne V. MarquartJochen BuechnerMatthias WölflPeter BaderFrontiers Media S.A.articleminimal residual disease (MRD)acute lymphoblastic leukaemia (ALL)haematopoietic stem cell transplantation (HSCT)childrenrelapsePediatricsRJ1-570ENFrontiers in Pediatrics, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	minimal residual disease (MRD) acute lymphoblastic leukaemia (ALL) haematopoietic stem cell transplantation (HSCT) children relapse Pediatrics RJ1-570
spellingShingle	minimal residual disease (MRD) acute lymphoblastic leukaemia (ALL) haematopoietic stem cell transplantation (HSCT) children relapse Pediatrics RJ1-570 Pietro Merli Marianne Ifversen Tony H. Truong Hanne V. Marquart Jochen Buechner Matthias Wölfl Peter Bader Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?
description	Minimal residual disease (MRD) assessment plays a central role in risk stratification and treatment guidance in paediatric patients with acute lymphoblastic leukaemia (ALL). As such, MRD prior to haematopoietic stem cell transplantation (HSCT) is a major factor that is independently correlated with outcome. High burden of MRD is negatively correlated with post-transplant survival, as both the risk of leukaemia recurrence and non-relapse mortality increase with greater levels of MRD. Despite growing evidence supporting these findings, controversies still exist. In particular, it is still not clear whether multiparameter flow cytometry and real-time quantitative polymerase chain reaction, which is used to recognise immunoglobulin and T-cell receptor gene rearrangements, can be employed interchangeably. Moreover, the higher sensitivity in MRD quantification offered by next-generation sequencing techniques may further refine the ability to stratify transplant-associated risks. While MRD quantification from bone marrow prior to HSCT remains the state of the art, heavily pre-treated patients may benefit from additional staging, such as using 18F-fluorodeoxyglucose positron emission tomography/computed tomography to detect focal residues of disease. Additionally, the timing of MRD detection (i.e., immediately before administration of the conditioning regimen or weeks before) is a matter of debate. Pre-transplant MRD negativity has previously been associated with superior outcomes; however, in the recent For Omitting Radiation Under Majority age (FORUM) study, pre-HSCT MRD positivity was associated with neither relapse risk nor survival. In this review, we discuss the level of MRD that may require pre-transplant therapy intensification, risking time delay and complications (as well as losing the window for HSCT if disease progression occurs), as opposed to an adapted post-transplant strategy to achieve long-term remission. Indeed, MRD monitoring may be a valuable tool to guide individualised treatment decisions, including tapering of immunosuppression, cellular therapies (such as donor lymphocyte infusions) or additional immunotherapy (such as bispecific T-cell engagers or chimeric antigen receptor T-cell therapy).
format	article
author	Pietro Merli Marianne Ifversen Tony H. Truong Hanne V. Marquart Jochen Buechner Matthias Wölfl Peter Bader
author_facet	Pietro Merli Marianne Ifversen Tony H. Truong Hanne V. Marquart Jochen Buechner Matthias Wölfl Peter Bader
author_sort	Pietro Merli
title	Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?
title_short	Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?
title_full	Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?
title_fullStr	Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?
title_full_unstemmed	Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?
title_sort	minimal residual disease prior to and after haematopoietic stem cell transplantation in children and adolescents with acute lymphoblastic leukaemia: what level of negativity is relevant?
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e0a0937ef4b44e059d9150d003ca4ae9
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Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?

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