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Results of successive EORTC‐CLG 58 881 and 58 951 trials in paediatric T‐cell acute lymphoblastic leukaemia (ALL)
Author(s) -
Hofmans Mattias,
Suciu Stefan,
Ferster Alina,
Van Vlierberghe Pieter,
Mazingue Françoise,
Sirvent Nicolas,
Costa Vitor,
Yakouben Karima,
Paillard Catherine,
Uyttebroeck Anne,
Plantaz Dominique,
Plat Geneviève,
Simon Pauline,
Millot Frédéric,
Poirée Marilyne,
van der Werff ten Bosch Jutte,
Piette Caroline,
Minckes Odile,
Rohrlich Pierre,
Girard Sandrine,
Cavé Hélène,
Bertrand Yves,
De Moerloose Barbara
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15983
Subject(s) - medicine , asparaginase , dexamethasone , prednisolone , chemotherapy , gastroenterology , incidence (geometry) , acute lymphocytic leukemia , hazard ratio , induction chemotherapy , surgery , leukemia , lymphoblastic leukemia , confidence interval , physics , optics
Summary 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/m 2 /day) versus prednisolone (60 mg/m 2 /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 × 10 9 /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 × 10 9 /l, representing approximately 50% of T‐ALL patients.

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