Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group

Background Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after firs...

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Autores: Ribera, JM, Garcia, O, Moreno, MJ, Barba, P, Garcia-Cadenas, I, Mercadal, S, Montesinos, P, Barrios, M, Gonzalez-Campos, J, Martinez-Carballeira, D, Gil, C, Ribera, J, Vives, S, Novo, A, Cervera, M, Serrano, J, Lavilla, E, Abella, E, Tormo, M, Amigo, ML, Artola, MT, Genesca, E, Bravo, P, Garcia-Belmonte, D, Garcia-Guinon, A, Hernandez-Rivas, JM, Feliu, E
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p6082
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones6082
Access Level:acceso abierto
Palabra clave:clinical disease recurrence
molecular disease recurrence
outcome
Philadelphia chromosome-positive acute lymphoblastic leukemia
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spelling Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA GroupRibera, JMGarcia, OMoreno, MJBarba, PGarcia-Cadenas, IMercadal, SMontesinos, PBarrios, MGonzalez-Campos, JMartinez-Carballeira, DGil, CRibera, JVives, SNovo, ACervera, MSerrano, JLavilla, EAbella, ETormo, MAmigo, MLArtola, MTGenesca, EBravo, PGarcia-Belmonte, DGarcia-Guinon, AHernandez-Rivas, JMFeliu, Eclinical disease recurrencemolecular disease recurrenceoutcomePhiladelphia chromosome-positive acute lymphoblastic leukemiaBackground Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763). Methods Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard-dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes. Results Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo-HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease-free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months [P = .05] and 28.7 months vs 11.5 months [P = .05] for DFS and OS, respectively). Conclusions Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.WILEY2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones6082CANCERISSN: 0008543XISSNe: 10970142reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p60822026-06-12T10:20:37Z
dc.title.none.fl_str_mv Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
title Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
spellingShingle Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
Ribera, JM
clinical disease recurrence
molecular disease recurrence
outcome
Philadelphia chromosome-positive acute lymphoblastic leukemia
title_short Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
title_full Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
title_fullStr Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
title_full_unstemmed Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
title_sort Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
dc.creator.none.fl_str_mv Ribera, JM
Garcia, O
Moreno, MJ
Barba, P
Garcia-Cadenas, I
Mercadal, S
Montesinos, P
Barrios, M
Gonzalez-Campos, J
Martinez-Carballeira, D
Gil, C
Ribera, J
Vives, S
Novo, A
Cervera, M
Serrano, J
Lavilla, E
Abella, E
Tormo, M
Amigo, ML
Artola, MT
Genesca, E
Bravo, P
Garcia-Belmonte, D
Garcia-Guinon, A
Hernandez-Rivas, JM
Feliu, E
author Ribera, JM
author_facet Ribera, JM
Garcia, O
Moreno, MJ
Barba, P
Garcia-Cadenas, I
Mercadal, S
Montesinos, P
Barrios, M
Gonzalez-Campos, J
Martinez-Carballeira, D
Gil, C
Ribera, J
Vives, S
Novo, A
Cervera, M
Serrano, J
Lavilla, E
Abella, E
Tormo, M
Amigo, ML
Artola, MT
Genesca, E
Bravo, P
Garcia-Belmonte, D
Garcia-Guinon, A
Hernandez-Rivas, JM
Feliu, E
author_role author
author2 Garcia, O
Moreno, MJ
Barba, P
Garcia-Cadenas, I
Mercadal, S
Montesinos, P
Barrios, M
Gonzalez-Campos, J
Martinez-Carballeira, D
Gil, C
Ribera, J
Vives, S
Novo, A
Cervera, M
Serrano, J
Lavilla, E
Abella, E
Tormo, M
Amigo, ML
Artola, MT
Genesca, E
Bravo, P
Garcia-Belmonte, D
Garcia-Guinon, A
Hernandez-Rivas, JM
Feliu, E
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv clinical disease recurrence
molecular disease recurrence
outcome
Philadelphia chromosome-positive acute lymphoblastic leukemia
topic clinical disease recurrence
molecular disease recurrence
outcome
Philadelphia chromosome-positive acute lymphoblastic leukemia
description Background Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763). Methods Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard-dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes. Results Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo-HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease-free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months [P = .05] and 28.7 months vs 11.5 months [P = .05] for DFS and OS, respectively). Conclusions Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones6082
url https://isabial.portalinvestigacion.com/publicaciones6082
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv CANCER
ISSN: 0008543X
ISSNe: 10970142
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
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