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Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation

SIMPLE SUMMARY: Upfront genetics/cytogenetics and minimal measurable disease (MRD) are becoming relevant biomarkers in the process of post-remission transplant allocation in AML. However, until recently the transplantation choice relied on the availability of a fully matched familiar donor, whereas...

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Autores principales: Buccisano, Francesco, Palmieri, Raffaele, Piciocchi, Alfonso, Maurillo, Luca, Del Principe, Maria Ilaria, Paterno, Giovangiacinto, Soddu, Stefano, Cerretti, Raffaella, De Angelis, Gottardo, Mariotti, Benedetta, Irno Consalvo, Maria Antonietta, Conti, Consuelo, Fraboni, Daniela, Divona, Mariadomenica, Ottone, Tiziana, Lavorgna, Serena, Panetta, Paola, Voso, Maria Teresa, Arcese, William, Venditti, Adriano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959451/
https://www.ncbi.nlm.nih.gov/pubmed/33802502
http://dx.doi.org/10.3390/cancers13051083
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author Buccisano, Francesco
Palmieri, Raffaele
Piciocchi, Alfonso
Maurillo, Luca
Del Principe, Maria Ilaria
Paterno, Giovangiacinto
Soddu, Stefano
Cerretti, Raffaella
De Angelis, Gottardo
Mariotti, Benedetta
Irno Consalvo, Maria Antonietta
Conti, Consuelo
Fraboni, Daniela
Divona, Mariadomenica
Ottone, Tiziana
Lavorgna, Serena
Panetta, Paola
Voso, Maria Teresa
Arcese, William
Venditti, Adriano
author_facet Buccisano, Francesco
Palmieri, Raffaele
Piciocchi, Alfonso
Maurillo, Luca
Del Principe, Maria Ilaria
Paterno, Giovangiacinto
Soddu, Stefano
Cerretti, Raffaella
De Angelis, Gottardo
Mariotti, Benedetta
Irno Consalvo, Maria Antonietta
Conti, Consuelo
Fraboni, Daniela
Divona, Mariadomenica
Ottone, Tiziana
Lavorgna, Serena
Panetta, Paola
Voso, Maria Teresa
Arcese, William
Venditti, Adriano
author_sort Buccisano, Francesco
collection PubMed
description SIMPLE SUMMARY: Upfront genetics/cytogenetics and minimal measurable disease (MRD) are becoming relevant biomarkers in the process of post-remission transplant allocation in AML. However, until recently the transplantation choice relied on the availability of a fully matched familiar donor, whereas individual patient- and disease-related characteristics played a secondary role in transplant allocation. In this paper we analyzed the evolution of the transplantation policy at our center in a 20-year time interval. At the beginning of our observation patients were submitted to allogeneic transplant, per protocol, mostly if a fully matched family donor was available or to autologous transplant if no fully matched family donor was identified (“donor vs. no donor” strategy) regardless of upfront genetics/cytogenetics or MRD status. Thereafter, persistence of MRD after consolidation cycle was included in the decision-making process for transplant selection. Patients with favorable and intermediate-risk cytogenetic risk were to receive allogeneic or autologous stem cell transplantation if MRD positive or negative, respectively, (“transplant vs. no transplant” strategy). In this cohort, patients with FLT3-ITD or adverse risk karyotype were submitted to allogeneic transplant as well. ABSTRACT: Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation.
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spelling pubmed-79594512021-03-16 Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation Buccisano, Francesco Palmieri, Raffaele Piciocchi, Alfonso Maurillo, Luca Del Principe, Maria Ilaria Paterno, Giovangiacinto Soddu, Stefano Cerretti, Raffaella De Angelis, Gottardo Mariotti, Benedetta Irno Consalvo, Maria Antonietta Conti, Consuelo Fraboni, Daniela Divona, Mariadomenica Ottone, Tiziana Lavorgna, Serena Panetta, Paola Voso, Maria Teresa Arcese, William Venditti, Adriano Cancers (Basel) Article SIMPLE SUMMARY: Upfront genetics/cytogenetics and minimal measurable disease (MRD) are becoming relevant biomarkers in the process of post-remission transplant allocation in AML. However, until recently the transplantation choice relied on the availability of a fully matched familiar donor, whereas individual patient- and disease-related characteristics played a secondary role in transplant allocation. In this paper we analyzed the evolution of the transplantation policy at our center in a 20-year time interval. At the beginning of our observation patients were submitted to allogeneic transplant, per protocol, mostly if a fully matched family donor was available or to autologous transplant if no fully matched family donor was identified (“donor vs. no donor” strategy) regardless of upfront genetics/cytogenetics or MRD status. Thereafter, persistence of MRD after consolidation cycle was included in the decision-making process for transplant selection. Patients with favorable and intermediate-risk cytogenetic risk were to receive allogeneic or autologous stem cell transplantation if MRD positive or negative, respectively, (“transplant vs. no transplant” strategy). In this cohort, patients with FLT3-ITD or adverse risk karyotype were submitted to allogeneic transplant as well. ABSTRACT: Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation. MDPI 2021-03-03 /pmc/articles/PMC7959451/ /pubmed/33802502 http://dx.doi.org/10.3390/cancers13051083 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Buccisano, Francesco
Palmieri, Raffaele
Piciocchi, Alfonso
Maurillo, Luca
Del Principe, Maria Ilaria
Paterno, Giovangiacinto
Soddu, Stefano
Cerretti, Raffaella
De Angelis, Gottardo
Mariotti, Benedetta
Irno Consalvo, Maria Antonietta
Conti, Consuelo
Fraboni, Daniela
Divona, Mariadomenica
Ottone, Tiziana
Lavorgna, Serena
Panetta, Paola
Voso, Maria Teresa
Arcese, William
Venditti, Adriano
Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation
title Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation
title_full Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation
title_fullStr Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation
title_full_unstemmed Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation
title_short Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation
title_sort use of measurable residual disease to evolve transplant policy in acute myeloid leukemia: a 20-year monocentric observation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959451/
https://www.ncbi.nlm.nih.gov/pubmed/33802502
http://dx.doi.org/10.3390/cancers13051083
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