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Haematologica. 2017 Oct;102(10):1727-1738. doi: 10.3324/haematol.2017.165845. Epub 2017 Jul 27.

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.

Author information

1
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent University, Belgium veerle.mondelaers@uzgent.be.
2
EORTC Headquarters, Brussels, Belgium.
3
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent University, Belgium.
4
Department of Pediatric Hematology-Oncology, Children's University Hospital Queen Fabiola, Université Libre de Bruxelles (ULB), Belgium.
5
Department of Pediatric Hematology-Oncology, CHRU, Lille, France.
6
Department of Pediatric Hematology-Oncology, CHU-Hopital Purpan, Toulouse, France.
7
Department of Pediatric Hematology, Robert Debré Hospital, AP-HP, Paris, France.
8
Department of Pediatric Hematology-Oncology, University Hospital Gasthuisberg, Leuven, Belgium.
9
Department of Pediatric Hematology-Oncology, University Hospital Hautepierre, Strasbourg, France.
10
Department of Pediatrics, Portuguese Oncology Institute, Porto, Portugal.
11
Department of Pediatric Hematology-Oncology, CHU, Montpellier, France.
12
Pediatric Hematology Unit, CHU Jean Minjoz Hospital, Besançon, France.
13
Department of Pediatric Hematology-Oncology, American Memorial Hospital, Reims, France.
14
Department of Pediatric Hematology-Oncology, CHU Lenval, Nice, France.
15
Department of Pediatric Hematology-Oncology, CHU, Caen, France.
16
Pediatric Oncology Unit, University Hospital, Poitiers, France.
17
Department of Pediatric Oncology, University Hospital, Grenoble, France.
18
Department of Pediatrics, University Hospital Antwerp, Belgium.
19
Department of Pediatrics, CHR de la Citadelle, Liège, Belgium.
20
Department of Genetics, Assistance Publique des Hôpitaux de Paris (AP-HP), Robert Debré Hospital, Paris, France.
21
INSERM UMR 1131, University Institute of Hematology, University Paris Diderot, Paris Sorbonne Cité, France.
22
Institute of Pediatric Hematology and Oncology (IHOP), Hospices Civils de Lyon, and University Lyon 1, France.

Abstract

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.

PMID:
28751566
PMCID:
PMC5622857
DOI:
10.3324/haematol.2017.165845
[Indexed for MEDLINE]
Free PMC Article

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