Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia

The treatment of AML in older adults is limited by the high mortality related with induction chemotherapy; however, those who tolerate an intensive treatment will have better outcomes; therefore, selecting this group of patients through the use of functionality scales is a fundamental part of the in...

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Autores:
Arévalo Zambrano, Mónica
Abello Polo, Virginia
Omaña Orduz, Olga Paola
Villamizar Gómez, Liceth
Tipo de recurso:
Article of journal
Fecha de publicación:
2018
Institución:
Fundación Universitaria de Ciencias de la Salud - FUCS
Repositorio:
Repositorio Digital Institucional ReDi
Idioma:
eng
OAI Identifier:
oai:repositorio.fucsalud.edu.co:001/1729
Acceso en línea:
https://repositorio.fucsalud.edu.co/handle/001/1729
Palabra clave:
Acute myeloid leukemia
Myelodysplastic syndrome
Azacitidine
Bone marrow transplantation
Trasplante de médula osea
Azacitidina
Síndromes mielodisplásicos
Leucemia mieloide aguda
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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dc.title.eng.fl_str_mv Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
title Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
spellingShingle Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
Acute myeloid leukemia
Myelodysplastic syndrome
Azacitidine
Bone marrow transplantation
Trasplante de médula osea
Azacitidina
Síndromes mielodisplásicos
Leucemia mieloide aguda
title_short Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
title_full Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
title_fullStr Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
title_full_unstemmed Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
title_sort Pre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia
dc.creator.fl_str_mv Arévalo Zambrano, Mónica
Abello Polo, Virginia
Omaña Orduz, Olga Paola
Villamizar Gómez, Liceth
dc.contributor.author.none.fl_str_mv Arévalo Zambrano, Mónica
Abello Polo, Virginia
Omaña Orduz, Olga Paola
Villamizar Gómez, Liceth
dc.subject.proposal.eng.fl_str_mv Acute myeloid leukemia
Myelodysplastic syndrome
Azacitidine
Bone marrow transplantation
topic Acute myeloid leukemia
Myelodysplastic syndrome
Azacitidine
Bone marrow transplantation
Trasplante de médula osea
Azacitidina
Síndromes mielodisplásicos
Leucemia mieloide aguda
dc.subject.decs.none.fl_str_mv Trasplante de médula osea
Azacitidina
Síndromes mielodisplásicos
Leucemia mieloide aguda
description The treatment of AML in older adults is limited by the high mortality related with induction chemotherapy; however, those who tolerate an intensive treatment will have better outcomes; therefore, selecting this group of patients through the use of functionality scales is a fundamental part of the initial therapeutic approach. Risk assessment scales have been designed and validated by other authors; in our country they have not been routinely used until now. Objective: To describe 8-week treatment related and 1- year mortality in AML patients, older than 60 years, after selecting treatment based on functionality risk scores (FRS), at two hospitals in Bogotá. Design: An observational study was performed, analyzing early mortality in two cohorts; a retrospective, including patients treated from 2010-2015 and a prospective one, from 2015 to 2018, in which the treatment was selected according FRS (SPPB, CCI and MD Anderson Predictive Score). Setting: Patients were treated in two university hospitals in Bogotá, Colombia. Patients: AML patients older than 60 years; acute promyelocytic leukemia patients were excluded. Interventions: FRS were assessed at diagnosis, high risk patients received supportive care, intermediate risk received 5-Azacitidine or low dose ARA-C, low risk patient wereconsidered eligible for standard induction chemotherapy (7+3). Main Outcomes Measures: We evaluated 8-week mortality as predicted by a combination of 3 different scales and compared it with a control retrospective cohort. Results: Sixty patients were included, median age 72 years (range: 62 - 84), 78% had intermediate cytogenetic risk and 20% high risk. 35% had a history of another hematological neoplasm. Only 38.3% received high intensity chemotherapy. Survival at 8 weeks was 70% without differences between treatment groups. One-year mortality was high, 73.9% of patients treated with 7x3 died, 80% in the low intensity group and 85.7% in the best support treatment. The ICC scale was predictive of 1-year mortality, but not the MD Anderson scale. Conclusions: In this high-risk group, 7+3 was well tolerated when patients were selected using FRS. The CCI scale was predictive of one-year mortality and could be used to optimize the selection of elderly patients with AML.
publishDate 2018
dc.date.issued.none.fl_str_mv 2018-09
dc.date.accessioned.none.fl_str_mv 2021-08-24T14:53:43Z
dc.date.available.none.fl_str_mv 2021-08-24T14:53:43Z
dc.type.spa.fl_str_mv Artículo de revista
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dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.citationendpage.spa.fl_str_mv S206
dc.relation.citationissue.spa.fl_str_mv 1
dc.relation.citationstartpage.spa.fl_str_mv S205
dc.relation.citationvolume.spa.fl_str_mv 18
dc.relation.cites.none.fl_str_mv Clinical lymphoma, myeloma and leukemia ISSN:2152-2650 Vol.18 Núm.1 (2018)
dc.relation.ispartofjournal.spa.fl_str_mv Clinical lymphoma, myeloma and leukemia
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.creativecommons.spa.fl_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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dc.format.extent.spa.fl_str_mv 2 p.
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dc.publisher.spa.fl_str_mv Elsevier
dc.publisher.place.spa.fl_str_mv Estados Unidos
dc.source.spa.fl_str_mv https://ur.booksc.eu/book/72643886/222f84
institution Fundación Universitaria de Ciencias de la Salud - FUCS
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spelling Arévalo Zambrano, Mónica166ddb5eaebfec60bb6a8275531232c0Abello Polo, Virginiabab7a56aea1042e6b6e3ab501be614bfOmaña Orduz, Olga Paola3be2df5215aad60a18692ee342be9b09Villamizar Gómez, Liceth2ceb9b276d75dc639a6fbb495aef5e4c2021-08-24T14:53:43Z2018-092021-08-24T14:53:43ZElsevierEstados UnidosThe treatment of AML in older adults is limited by the high mortality related with induction chemotherapy; however, those who tolerate an intensive treatment will have better outcomes; therefore, selecting this group of patients through the use of functionality scales is a fundamental part of the initial therapeutic approach. Risk assessment scales have been designed and validated by other authors; in our country they have not been routinely used until now. Objective: To describe 8-week treatment related and 1- year mortality in AML patients, older than 60 years, after selecting treatment based on functionality risk scores (FRS), at two hospitals in Bogotá. Design: An observational study was performed, analyzing early mortality in two cohorts; a retrospective, including patients treated from 2010-2015 and a prospective one, from 2015 to 2018, in which the treatment was selected according FRS (SPPB, CCI and MD Anderson Predictive Score). Setting: Patients were treated in two university hospitals in Bogotá, Colombia. Patients: AML patients older than 60 years; acute promyelocytic leukemia patients were excluded. Interventions: FRS were assessed at diagnosis, high risk patients received supportive care, intermediate risk received 5-Azacitidine or low dose ARA-C, low risk patient wereconsidered eligible for standard induction chemotherapy (7+3). Main Outcomes Measures: We evaluated 8-week mortality as predicted by a combination of 3 different scales and compared it with a control retrospective cohort. Results: Sixty patients were included, median age 72 years (range: 62 - 84), 78% had intermediate cytogenetic risk and 20% high risk. 35% had a history of another hematological neoplasm. Only 38.3% received high intensity chemotherapy. Survival at 8 weeks was 70% without differences between treatment groups. One-year mortality was high, 73.9% of patients treated with 7x3 died, 80% in the low intensity group and 85.7% in the best support treatment. The ICC scale was predictive of 1-year mortality, but not the MD Anderson scale. Conclusions: In this high-risk group, 7+3 was well tolerated when patients were selected using FRS. The CCI scale was predictive of one-year mortality and could be used to optimize the selection of elderly patients with AML.https://ur.booksc.eu/book/72643886/222f842 p.application/pdfPre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid LeukemiaArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTexthttps://purl.org/redcol/resource_type/WPhttp://purl.org/coar/version/c_970fb48d4fbd8a85https://repositorio.fucsalud.edu.co/handle/001/1729enginfo:eu-repo/semantics/openAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)https://creativecommons.org/licenses/by-nd/4.0/http://purl.org/coar/access_right/c_abf2Acute myeloid leukemiaMyelodysplastic syndromeAzacitidineBone marrow transplantationTrasplante de médula oseaAzacitidinaSíndromes mielodisplásicosLeucemia mieloide agudaS2061S20518Clinical lymphoma, myeloma and leukemia 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Acute Myeloid Leukemia.pdf.jpgPre-Treatment Risk Assessment for Elderly Patients with Acute Myeloid Leukemia.pdf.jpgGenerated Thumbnailimage/jpeg18023https://repositorio.fucsalud.edu.co/bitstreams/c3902503-f91b-4c6e-9639-2b8edf91a8e4/download3b69d6719bdb1c9e3b48bed81c9c47f5MD54001/1729oai:repositorio.fucsalud.edu.co:001/17292024-02-02 13:07:05.201https://creativecommons.org/licenses/by-nd/4.0/open.accesshttps://repositorio.fucsalud.edu.coRepositorio Digital de la Fundación Universitaria de Ciencias de la 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