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

Huguet, Françoise; Chevret, Sylvie; Leguay, Thibaut; Thomas, Xavier; Boissel, Nicolas; Escoffre-Barbe, Martine; Chevallier, Patrice; Hunault, Mathilde; Vey, Norbert; Bonmati, Caroline; Lepretre, Stéphane; Marolleau, Jean-Pierre; Pabst Müller, Thomas Niklaus; Rousselot, Philippe; Buzyn, Agnès; Cahn, Jean-Yves; Lhéritier, Véronique; Béné, Marie C; Asnafi, Vahid; Delabesse, Eric; ... (2018). Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial. Journal of clinical oncology, 36(24), pp. 2514-2523. American Society of Clinical Oncology 10.1200/JCO.2017.76.8192

[img]
Preview
Text
jco.2017.76.8192.pdf - Published Version
Available under License Publisher holds Copyright.

Download (915kB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Pabst Müller, Thomas Niklaus

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0732-183X

Publisher:

American Society of Clinical Oncology

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

07 Mar 2019 15:28

Last Modified:

24 Oct 2019 20:02

Publisher DOI:

10.1200/JCO.2017.76.8192

PubMed ID:

29863974

BORIS DOI:

10.7892/boris.124031

URI:

https://boris.unibe.ch/id/eprint/124031

Actions (login required)

Edit item Edit item
Provide Feedback