Age-adapted chemotherapy and MRD-oriented transplant for Ph-negative acute lymphoblastic leukemia: the GRAALL-2014 trial
Year: 2025
Type: article
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.
Source: Blood
Authors: Nicolas Boissel, Sylvie Chevret, Françoise Huguet, Thibaut Leguay, Mathilde Hunault, Carlos Graux, Yves Chalandon, Eric Delabesse, Yosr Hicheri, Patrice Chevallier, Marie Balsat, Cédric Pastoret, Martine Escoffre-Barbe, Florence Pasquier, Magalie Joris, Anne Thiebaut, Anne Huynh, Nathalie Dhédin, Emilie Lemasle, Caroline Bonmati, Sébastien Maury, Gaëlle Guillerm, Ana Berceanu, Markus Manz, Thomas Cluzeau, Pascal Turlure, Philippe Rousselot, Bernard de Prijck, Nathalie Grardel, Marie C. Béné, Marina Lafage-Pochitaloff, Wendy Cuccuini, Norbert Ifrah, Véronique Lhéritier, Vahid Asnafi, Emmanuelle Clappier, Hervé Dombret
Institutions: Inserm, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Institut de recherche Saint-Louis, Centre Hospitalier Universitaire de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Centre Hospitalier Universitaire de Bordeaux, Hôpital Cardiologique du Haut-Lévêque, Centre Hospitalier Universitaire d'Angers, CHU Dinant Godinne UCL Namur, UCLouvain, University Hospital of Geneva, Centre de Recherches en Cancérologie de Toulouse, Université de Toulouse, Institut Paoli-Calmettes, Centre Hospitalier Universitaire de Nantes, Hôpital Lyon Sud, Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Institut Gustave Roussy, Centre Hospitalier Universitaire Amiens-Picardie, Centre Hospitalier Universitaire de Grenoble, Centre Henri Becquerel, Centre Hospitalier Régional et Universitaire de Nancy, Centre Hospitalier Universitaire Henri-Mondor, Hôpitaux Universitaires Henri-Mondor, Centre Hospitalier Régional Universitaire de Brest, Centre Hospitalier Universitaire de Besançon, University of Zurich, University Hospital Zurich, Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Limoges, Centre Hospitalier de Versailles, University of Liège, Centre Hospitalier Universitaire de Liège, Centre Hospitalier Universitaire de Lille, Aix-Marseille Université, Hôpital de la Timone, Institut National du Cancer, Hôpital Necker-Enfants Malades
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4415526654