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

Authors :
Huguet F
Chevret S
Leguay T
Thomas X
Boissel N
Escoffre-Barbe M
Chevallier P
Hunault M
Vey N
Bonmati C
Lepretre S
Marolleau JP
Pabst T
Rousselot P
Buzyn A
Cahn JY
Lhéritier V
Béné MC
Asnafi V
Delabesse E
Macintyre E
Chalandon Y
Ifrah N
Dombret H
Source :
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2018 Aug 20; Vol. 36 (24), pp. 2514-2523. Date of Electronic Publication: 2018 Jun 04.
Publication Year :
2018

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.

Details

Language :
English
ISSN :
1527-7755
Volume :
36
Issue :
24
Database :
MEDLINE
Journal :
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Publication Type :
Academic Journal
Accession number :
29863974
Full Text :
https://doi.org/10.1200/JCO.2017.76.8192