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Br J Haematol. 2019 May 24. doi: 10.1111/bjh.15983. [Epub ahead of print]

Results of successive EORTC-CLG 58 881 and 58 951 trials in paediatric T-cell acute lymphoblastic leukaemia (ALL).

Author information

1
Paediatric Haematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
2
Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
3
EORTC Headquarters, Brussels, Belgium.
4
Department of Paediatric Haematology-Oncology, Children's University Hospital Queen Fabiola, Université Libre de Bruxelles, Brussels, Belgium.
5
Cancer Research Institute Ghent, Ghent, Belgium.
6
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
7
Department of Paediatric Haematology-Oncology, Centre Hospitalo-Universitaire de Lille, Lille, France.
8
Department of Paediatric Haematology-Oncology, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.
9
University Montpellier, Montpellier, France.
10
Paediatric Department, Instituto Português de Oncologia, Porto, Portugal.
11
Department of Paediatric Haematology, Hôpital Robert Debré, AP-HP, Paris, France.
12
Department of Paediatric Haematology and Oncology, Centre Hospitalo-Universitaire de Strasbourg, Strasbourg, France.
13
Department of Paediatric Haematology-Oncology, University Hospital Gasthuisberg, Leuven, Belgium.
14
Department of Paediatric Oncology, University Hospital, Grenoble, France.
15
Department of Paediatric Haematology-Oncology, Centre Hospitalo-Universitaire, Hopital Purpan, Toulouse, France.
16
Service Hématologie Oncologie Pédiatrique, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
17
Paediatric Oncology Unit, University Hospital, Poitiers, France.
18
Department of Paediatric Haematology-Oncology, Centre Hospitalo-Universitaire de Nice, Nice, France.
19
Department of Paediatrics, Universitair Ziekenhuis Brussel, Brussels, Belgium.
20
Service Universitaire d'Hémato-Oncologie Pédiatrique Liégeois (SUHOPL), CHR Citadelle, Liège, Belgium.
21
Department of Paediatric Haematology-Oncology, Centre Hospitalo-Universitaire de Caen, Caen, France.
22
Laboratory of Haematology, Institute of Paediatric Haematology and Oncology (IHOP), Hospices Civils de Lyon, Lyon, France.
23
Département de Génétique, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Paris, France.
24
INSERM UMR_S1131, Institut de Recherche Saint-Louis, Université Paris Diderot, Paris, France.
25
Institute of Paediatric Haematology and Oncology (IHOP), Haematology Unit, Hospices Civils de Lyon and Claude Bernard University, Lyon, France.

Abstract

Outcomes in childhood T-cell acute lymphoblastic leukaemia (T-ALL) are steadily improving due to intensive therapy. Between 1989 and 2008, 599 children with newly diagnosed T-ALL were enrolled in two successive European Organization for Research and Treatment of Cancer - Children's Leukaemia Group trials (58881 and 58951), both based on the Berlin-Frankfurt-Munster protocol and without cranial irradiation. In the latter trial induction chemotherapy was intensified. The most important randomizations were Medac Escherichia coli asparaginase versus Erwinia asparaginase in trial 58881, and dexamethasone (6 mg/m2 /day) versus prednisolone (60 mg/m2 /day) and prolonged versus conventional asparaginase duration in trial 58951. 8-year event-free survival (EFS) increased from 65·1% to 74·0% in trial 58951. Improvement was most profound for patients with white blood cell (WBC) counts <100 × 109 /l and "good responders" to prephase. Medac E. coli asparaginase was associated with longer EFS [hazard ratio (HR) 0·54, P = 0·0015] and overall survival (HR 0·51, P = 0·0018). Induction therapy with dexamethasone did not improve EFS compared to prednisolone. Remarkably, intensification of central nervous system (CNS)-directed therapy in trial 58951 resulted in fewer bone marrow relapses, while the incidence of CNS relapses remained low. In summary, we showed that adequate asparaginase therapy, intensified induction treatment and intensification of CNS-directed chemotherapy can result in an improvement of outcome in T-ALL patients with good prephase response and initial WBC counts <100 × 109 /l, representing approximately 50% of T-ALL patients.

KEYWORDS:

EORTC; T-cell acute lymphoblastic leukaemia; asparaginase; childhood leukaemia; cranial radiotherapy

PMID:
31124581
DOI:
10.1111/bjh.15983

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