Age-adapted chemotherapy and MRD-oriented transplant for Ph-negative acute lymphoblastic leukemia: the GRAALL-2014 trial
Abstract
Abstract The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL)-2014 trial evaluated an intensive, age-adapted protocol for adults aged 18 to 59 years with Philadelphia chromosome negative acute lymphoblastic leukemia. The trial was motivated by findings from the previous GRAALL-2005 study, which reported excessive toxicity from pediatric-inspired therapy in older patients and no added benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT) among those with an early favorable response to treatment. Thus, the GRAALL-2014 protocol aimed to reduce treatment-related toxicity in patients aged ≥45 years and to limit allo-HSCT to patients with poor measurable residual disease (MRD) responses. A total of 743 patients were included, and outcomes were compared with those of GRAALL-2005 trial. The GRAALL-2014 study demonstrated reduced early mortality and higher complete remission rates in patients aged ≥45 years. MRD-guided transplantation decisions reduced allo-HSCT indications by ∼50%. Although older patients experienced a higher cumulative incidence of relapse, no significant difference in disease-free survival (DFS) was observed compared with historical cohorts across age subgroups. The overall 4-year DFS was 57.1% (95% confidence interval [CI], 53.4-61.1). Notably, 4-year overall survival improved significantly, from 65.5% (95% CI, 61.7-69.8) to 71.7% (95% CI, 67.7-76.0) in younger patients (P = .031) and from 49.6% (95% CI, 43.5-56.5) to 59.5% (95% CI, 53.5-66.3) in older patients (P = .011). These findings highlight the value of individualized treatment strategies that balance efficacy and safety. Future studies should investigate the integration of immunotherapy to further reduce treatment intensity and improve outcomes. This trial was registered at www.clinicaltrials.gov as #NCT02617004 and #NCT02619630.
Article Details
Authors (37)
Nicolas Boissel
Sylvie Chevret
Françoise Huguet
3Service d’Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Thibaut Leguay
Mathilde Hunault
2Department of Hematology, Centre Hospitalier Universitaire d’Angers, INSERM, Centre National de la Recherche Scientifique, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Fédération Hospitalo-Universitaire Grand Ouest Against Leukemia, Université d’Angers, Université de Nantes, Angers, France
Carlos Graux
31Service d’Hématologie, Centre Hospitalier Universitaire, Université Catholique de Louvain Namur–Site Godinne, Yvoir, Belgium
Yves Chalandon
25Swiss Group for Clinical Cancer Research, Bern, Switzerland
Éric Delabesse
26Laboratory of Hematology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Yosr Hicheri
7Service d’Hématologie, Institut Paoli-Calmettes, Marseille, France
Patrice Chevallier
Service d’Hématologie, Centre Hospitalier Universitaire (CHU) Hôtel Dieu, Nantes, France
Marie Balsat
9Service d’Hématologie, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France
Cédric Pastoret
10Laboratoire d’Hématologie, Centre Hospitalier Universitaire de Rennes, Rennes, France
Martine Escoffre-Barbe
Service Hématologie, Hôpital Universitaire de Rennes, Rennes, France
Florence Pasquier
Magalie Joris
16Department of Hematology, Centre Hospitalier Universitaire d'Amiens, Amiens, France
Anne Thiébaut
Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
Anne Huynh
5Department of Hematology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Nathalie Dhédin
1Department of Adolescent and Young Adult Hematology, Saint-Louis University Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France
Emilie Lemasle
17Department of Hematology, Centre Henri Becquerel, Rouen, France
Caroline Bonmati
19Department of Hematology, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-les-Nancy, France
Sébastien Maury
12Service d’Hématologie Clinique, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Paris, France
Gaëlle Guillerm
21Department of Hematology, Centre Hospitalier Universitaire de Brest, Brest, France
Ana Berceanu
22Department of Clinical Hematology, Centre Hospitalier Universitaire de Besançon, Besançon, France
Markus Manz
23Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
Thomas Cluzeau
15Service d’Hématologie, Centre Hospitalier Universitaire de Nice, Nice, France
Pascal Turlure
16Department of Hematology, Centre Hospitalier Universitaire de Limoges, Limoges, France
Philippe Rousselot
Bernard De Prijck
Service Hématologie, Hôpital Universitaire de Liège, Liège, Belgium
Nathalie Grardel
28Laboratory of Hematology, Centre Hospitalier Universitaire Lille, Lille, France
Marie C. Béné
11Department of Hematology, Centre Hospitalier Universitaire de Nantes, Nantes, France
Marina Lafage-Pochitaloff
29Hematological Cytogenetics Laboratory, Timone Hospital, Aix Marseille University, Marseille, France
Wendy Cuccuini
30Groupe Francophone de Cytogénétique Hématologique, Paris, France
Norbert Ifrah
2Department of Hematology, Centre Hospitalier Universitaire d’Angers, INSERM, Centre National de la Recherche Scientifique, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Fédération Hospitalo-Universitaire Grand Ouest Against Leukemia, Université d’Angers, Université de Nantes, Angers, France
Véronique Lhéritier
30Group for Research on Adult Acute Lymphoblastic Leukemia, Hôpital Lyon Sud, Pierre-Bénite, France
Vahid Asnafi
Université Paris Cité
Emmanuelle Clappier
2Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
Hervé Dombret