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Article dans une revue

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 Norbert Vey 8 Caroline Bonmati 9 Stéphane Leprêtre 10 Jean-Pierre Marolleau 11 Thomas Pabst 12 Philippe Rousselot 13 Agnes Buzyn 14 Jean-Yves Cahn 15 Véronique Lheritier 16 Marie Béné Vahid Asnafi 17 Eric Delabesse 18 Elizabeth Macintyre 17 Yves Chalandon 19 Norbert Ifrah Hervé Dombret 20 
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 : jeudi 1 septembre 2022 - 03:55:30


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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, American Society of Clinical Oncology, 2018, 36 (24), pp.2514-2523. ⟨10.1200/JCO.2017.76.8192⟩. ⟨hal-02874609⟩



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