System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print 1 citation

PubMed: 41135009 DOI: 10.1182/blood.2025029611

Age-adapted chemotherapy and MRD-oriented transplant for Ph-negative acute lymphoblastic leukemia: the GRAALL-2014 trial.

Blood

Authors: Nicolas Boissel, Sylvie Chevret, Françoise Rigal-Huguet, Thibaut Tl Leguay, Mathilde Hunault, Carlos Graux, Yves Chalandon, Eric Delabesse, Yosr Hicheri, Patrice Chevallier, Marie Balsat, Cedric Pastoret, Martine Escoffre-Barbe, Florence Pasquier, Magalie Joris, Anne Thiebaut, Anne Huynh, Nathalie Dhedin, Emilie Lemasle, Caroline Bonmati, Sebastien Maury, Gaelle Guillerm, Ana Berceanu, Urs Schanz, Thomas Cluzeau, Pascal Turlure, Philippe Rousselot, Bernard De Prijck, Nathalie Grardel, Marie-Christine Béné, Marina Lafage-Pochitaloff, Wendy Cuccuini, Norbert H Ifrah, Véronique Lheritier, Vahid Asnafi, Emmanuelle Clappier, Hervé Dombret

Affiliations

  • Hopital Saint-Louis, AP-HP, Paris, France.
  • saint louis hospital, paris, France.
  • Institut de Cancérologie de Toulouse, TOULOUSE, France.
  • Hopital du Haut-Lévèque, Pessac, France.
  • CHU, Angers, France.
  • CHU UCL Namur - Godinne, Yvoir, Belgium.
  • University Hospital of Geneva, Geneva, Switzerland.
  • University hospital of Toulouse, university of Toulouse 3, Center of Research on Cancer of Toulouse, Toulouse, France.
  • Institut Paoli Calmettes, MARSEILLE, France.
  • Centre Hospitalo-Universitaire, Nantes, France.
  • Hôpital Lyon sud, Pierre Benite, France.
  • Rennes University Hospital, RENNES, France.
  • CHU Rennes, RENNES, France.
  • Gustave Roussy, Villejuif, France.
  • CHU Amiens, Amiens, France.
  • CHU de Grenoble, Grenoble cedex 09, France.
  • IUCT Oncopole, TOULOUSE, France.
  • SAINT LOUIS HOSPITAL, PARIS, France.
  • centre Henri Becquerel, Rouen, France.
  • Service d'Hématologie, Centre Hospitalier Universitaire de Nancy, Nancy, France.
  • Hopital Henri Mondor, Créteil, France.
  • CHRU Brest, Brest, France.
  • Besançon University Hospital, Besançon, France.
  • University Hospital of Zurich, Zurich, Switzerland.
  • Côte d'Azur university, CHU of Nice, Nice, France.
  • chu limoges, limoges, France.
  • Centre Hospitalier de Versailles, University Versailles Paris-Saclay, Le Chesnay Rocquencourt, France.
  • CHU de Liège, Liège, Belgium.
  • CHRU de lille, LILLE, France.
  • University Hospital Nantes, Nantes, France.
  • Aix-Marseille University, Marseille, France.
  • Saint-Louis Hospital, Paris, France.
  • Institut National du Cancer, Angers, France.
  • Centre Hospitalier Lyon Sud, Pierre Bénite, France.
  • Laboratory of Onco-Hematology, Assistance Publique-Hopitaux De Paris (AP-HP), Hopital Necker Enfants-Malades, Paris, France.
  • Saint-Louis Hospital, AP-HP, Paris, France.
  • Paris Saint-Louis Leukemia Institute, Université Paris Cité, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.

Abstract

The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL)-2014 trial (ClinicalTrials.gov: NCT02617004, NCT02619630) evaluated an intensive, age-adapted protocol for adults aged 18-59 years with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). 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 (alloHSCT) in 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 alloHSCT to patients with poor measurable residual disease (MRD) responses. A total of 743 patients was included, and outcomes were compared to those of the GRAALL-2005 trial. The GRAALL-2014 demonstrated reduced early mortality and higher complete remission rates in patients aged ≥45 years. MRD-guided transplant decisions reduced alloHSCT indications by approximately 50%. While older patients experienced a higher cumulative incidence of relapse, no significant difference in disease-free survival (DFS) was observed compared to historical cohorts across age subgroups. The overall 4-year DFS was 57.1% (95% 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=0.031) and from 49.6% (95%CI, 43.5-56.5) to 59.5% (95%CI, 53.5-66.3) in older patients (p=0.011). These findings highlight the value of individualized treatment strategies, balancing efficacy and safety. Future studies should investigate the integration of immunotherapy to further reduce treatment intensity and improve outcomes.

MeSH

Precursor Cell Lymphoblastic Leukemia-Lymphoma, Hematology, Leukemia, Drug Therapy, Aged, Transplants, Therapeutics, Chemotherapy

Cited by