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Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951
Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of non-very high-risk patients by comparing prolonged (long-asparaginase) versus standard (short-asparagi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ferrata Storti Foundation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622857/ https://www.ncbi.nlm.nih.gov/pubmed/28751566 http://dx.doi.org/10.3324/haematol.2017.165845 |
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author | Mondelaers, Veerle Suciu, Stefan De Moerloose, Barbara Ferster, Alina Mazingue, Françoise Plat, Geneviève Yakouben, Karima Uyttebroeck, Anne Lutz, Patrick Costa, Vitor Sirvent, Nicolas Plouvier, Emmanuel Munzer, Martine Poirée, Maryline Minckes, Odile Millot, Frédéric Plantaz, Dominique Maes, Philip Hoyoux, Claire Cavé, Hélène Rohrlich, Pierre Bertrand, Yves Benoit, Yves |
author_facet | Mondelaers, Veerle Suciu, Stefan De Moerloose, Barbara Ferster, Alina Mazingue, Françoise Plat, Geneviève Yakouben, Karima Uyttebroeck, Anne Lutz, Patrick Costa, Vitor Sirvent, Nicolas Plouvier, Emmanuel Munzer, Martine Poirée, Maryline Minckes, Odile Millot, Frédéric Plantaz, Dominique Maes, Philip Hoyoux, Claire Cavé, Hélène Rohrlich, Pierre Bertrand, Yves Benoit, Yves |
author_sort | Mondelaers, Veerle |
collection | PubMed |
description | Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of non-very high-risk patients by comparing prolonged (long-asparaginase) versus standard (short-asparaginase) native E. coli asparaginase treatment in a randomized part of the phase III 58951 trial of the European Organization for Research and Treatment of Cancer Children’s Leukemia Group. The main endpoint was disease-free survival. Overall, 1,552 patients were randomly assigned to long-asparaginase (775 patients) or short-asparaginase (777 patients). Patients with grade ≥2 allergy to native E. coli asparaginase were switched to equivalent doses of Erwinia or pegylated E. coli asparaginase. The 8-year disease-free survival rate (±standard error) was 87.0±1.3% in the long-asparaginase group and 84.4±1.4% in the short-asparaginase group (hazard ratio: 0.87; P=0.33) and the 8-year overall survival rate was 92.6±1.0% and 91.3±1.2% respectively (hazard ratio: 0.89; P=0.53). An exploratory analysis suggested that the impact of long-asparaginase was beneficial in the National Cancer Institute standard-risk group with regards to disease-free survival (hazard ratio: 0.70; P=0.057), but far less so with regards to overall survival (hazard ratio: 0.89). The incidences of grade 3–4 infection during consolidation (25.2% versus 14.4%) and late intensification (22.6% versus 15.9%) and the incidence of grade 2–4 allergy were higher in the long-asparaginase arm (30% versus 21%). Prolonged native E. coli asparaginase therapy in consolidation and late intensification for our non-very high-risk patients did not improve overall outcome but led to an increase in infections and allergy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. |
format | Online Article Text |
id | pubmed-5622857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-56228572017-10-10 Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 Mondelaers, Veerle Suciu, Stefan De Moerloose, Barbara Ferster, Alina Mazingue, Françoise Plat, Geneviève Yakouben, Karima Uyttebroeck, Anne Lutz, Patrick Costa, Vitor Sirvent, Nicolas Plouvier, Emmanuel Munzer, Martine Poirée, Maryline Minckes, Odile Millot, Frédéric Plantaz, Dominique Maes, Philip Hoyoux, Claire Cavé, Hélène Rohrlich, Pierre Bertrand, Yves Benoit, Yves Haematologica Article Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of non-very high-risk patients by comparing prolonged (long-asparaginase) versus standard (short-asparaginase) native E. coli asparaginase treatment in a randomized part of the phase III 58951 trial of the European Organization for Research and Treatment of Cancer Children’s Leukemia Group. The main endpoint was disease-free survival. Overall, 1,552 patients were randomly assigned to long-asparaginase (775 patients) or short-asparaginase (777 patients). Patients with grade ≥2 allergy to native E. coli asparaginase were switched to equivalent doses of Erwinia or pegylated E. coli asparaginase. The 8-year disease-free survival rate (±standard error) was 87.0±1.3% in the long-asparaginase group and 84.4±1.4% in the short-asparaginase group (hazard ratio: 0.87; P=0.33) and the 8-year overall survival rate was 92.6±1.0% and 91.3±1.2% respectively (hazard ratio: 0.89; P=0.53). An exploratory analysis suggested that the impact of long-asparaginase was beneficial in the National Cancer Institute standard-risk group with regards to disease-free survival (hazard ratio: 0.70; P=0.057), but far less so with regards to overall survival (hazard ratio: 0.89). The incidences of grade 3–4 infection during consolidation (25.2% versus 14.4%) and late intensification (22.6% versus 15.9%) and the incidence of grade 2–4 allergy were higher in the long-asparaginase arm (30% versus 21%). Prolonged native E. coli asparaginase therapy in consolidation and late intensification for our non-very high-risk patients did not improve overall outcome but led to an increase in infections and allergy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. Ferrata Storti Foundation 2017-10 /pmc/articles/PMC5622857/ /pubmed/28751566 http://dx.doi.org/10.3324/haematol.2017.165845 Text en Copyright© 2017 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Article Mondelaers, Veerle Suciu, Stefan De Moerloose, Barbara Ferster, Alina Mazingue, Françoise Plat, Geneviève Yakouben, Karima Uyttebroeck, Anne Lutz, Patrick Costa, Vitor Sirvent, Nicolas Plouvier, Emmanuel Munzer, Martine Poirée, Maryline Minckes, Odile Millot, Frédéric Plantaz, Dominique Maes, Philip Hoyoux, Claire Cavé, Hélène Rohrlich, Pierre Bertrand, Yves Benoit, Yves Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 |
title | Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 |
title_full | Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 |
title_fullStr | Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 |
title_full_unstemmed | Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 |
title_short | Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951 |
title_sort | prolonged versus standard native e. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-hodgkin lymphoma: final results of the eortc-clg randomized phase iii trial 58951 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622857/ https://www.ncbi.nlm.nih.gov/pubmed/28751566 http://dx.doi.org/10.3324/haematol.2017.165845 |
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