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Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial

Francoise Huguet 1 Sylvie Chevret 2 Thibaut Leguay 3 Xavier Thomas 4 Nicolas Boissel 5 Martine Escoffre-Barbe 6 Patrice Chevallier 7 Mathilde Hunault-Berger 8 Norbert Vey 9 Caroline Bonmati 10 Stéphane Leprêtre 11 Jean-Pierre Marolleau 12 Thomas Pabst 13 Philippe Rousselot 14 Agnes Buzyn 15 Jean-Yves Cahn 16 Véronique Lheritier 17 Marie Béné 18 Vahid Asnafi 19 Eric Delabesse 20 Elizabeth Macintyre 19 Yves Chalandon 21 Norbert Ifrah 8 Hervé Dombret 22
Abstract :

Purpose To evaluate randomly the role of hyperfractionated cyclophosphamide (hyper-C) dose intensification in adults with newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol and to determine the upper age limit for treatment tolerability in this context. Patients and Methods A total of 787 evaluable patients (B/T lineage, 525 and 262, respectively; median age, 36.1 years) were randomly assigned to receive a standard dose of cyclophosphamide or hyper-C during first induction and late intensification. Compliance with chemotherapy was assessed by median doses actually received during each treatment phase by patients potentially exposed to the full planned doses. Results Overall complete remission (CR) rate was 91.9%. With a median follow-up of 5.2 years, the 5-year rate of event-free survival (EFS) and overall survival (OS) was 52.2% (95% CI, 48.5% to 55.7%) and 58.5% (95% CI, 54.8% to 61.9%), respectively. Randomization to the hyper-C arm did not increase the CR rate or prolong EFS or OS. As a result of worse treatment tolerance, advanced age continuously affected CR rate, EFS, and OS, with 55 years as the best age cutoff. At 5 years, EFS was 55.7% (95% CI, 51.8% to 59.4%) for patients younger than 55 years of age versus 25.8% (95% CI, 19.9% to 35.6%) in older patients (hazard ratio, 2.16; P < .001). Patients ≥ 55 years of age, in whom a lower compliance to the whole planned chemotherapy was observed, benefited significantly from hyper-C, whereas younger patients did not. Conclusion No significant benefit was associated with the introduction of a hyper-C sequence into a frontline pediatric-like adult acute lymphoblastic leukemia therapy. Overall, tolerability of an intensive pediatric-derived treatment was poor in patients ≥ 55 years of age.

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Soumis le : mercredi 24 juin 2020 - 15:05:13
Dernière modification le : vendredi 10 juillet 2020 - 13:36:02


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Francoise Huguet, Sylvie Chevret, Thibaut Leguay, Xavier Thomas, Nicolas Boissel, et al.. Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018, 36 (24), pp.2514-2523. ⟨10.1200/JCO.2017.76.8192⟩. ⟨hal-02874609⟩



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