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

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.

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Journal
Blood
Published
2025-10-24
DOI
https://doi.org/10.1182/blood.2025029611
Citations
3
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
5.64
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article

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

Mathilde Hunault, Françoise Rigal‐Huguet, Véronique Lhéritier, Éric Delabesse et al.
3 citations
Blood
Acute Lymphoblastic Leukemia research
5.64
article

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

Mathilde Hunault, Françoise Rigal‐Huguet, Véronique Lhéritier, Éric Delabesse, Marie Balsat, Sébastien Maury, Carlos Graux, Caroline Bonmati, Emmanuelle Clappier, Gaëlle Guillerm, Pascal Turlure, Émilie Lemasle, Nathalie Grardel, Patrice Chevallier, Anne Huynh, Thibaut Leguay, Wendy Cuccuini, Yosr Hicheri, Mårina Lafage‐Pochitaloff, Anne Thiebaut, Philippe Rousselot, Sylvie Chevret, Bernard De Prijck, Hervé Dombret, Marie C. Béné, Martine Escoffre‐Barbe, Nathalie Dhédin, Nicolas Boissel, Thomas Cluzeau, Cédric Pastoret, Yves Chalandon, Ana Berceanu, Florence Pasquier, Norbert H Ifrah, Vahid Asnafi, Magalie Joris
article en
3 citations

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.

BloodVol. 147(8)
Délégation Paris 5 (FR), University of Geneva (CH), Hôpital Necker-Enfants Malades (FR), Inserm (FR), Université Paris Cité (FR), Aix-Marseille Université (FR), Centre Hospitalier Universitaire de Grenoble (FR), Institut Gustave Roussy (FR), Saint Louis University Hospital (US), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire de Toulouse (FR), Centre de Recherches en Cancérologie de Toulouse (FR), Centre Hospitalier Universitaire de Besançon (FR), Université Sorbonne Paris Nord (FR), CHU Dinant Godinne UCL Namur (BE), Hôpital Beau-Séjour (CH), Acute Leukemia French Association (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Intergroupe Francophone de Cancérologie Thoracique (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), University Hospital of Zurich (CH), University Hospital of Geneva (CH), Centre Hospitalier Universitaire d'Angers (FR), Hôpital Lyon Sud (FR), Centre Hospitalier Universitaire de Limoges (FR), Hôpital Cardiologique du Haut-Lévêque (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier Régional Universitaire de Brest (FR), Centre Hospitalier Universitaire de Liège (BE), Laboratoire National Henri Becquerel (FR), Hôpital Saint-Louis (FR), Institut National du Cancer (FR), Institut Paoli-Calmettes (FR), Centre Hospitalier Universitaire de Rennes (FR), Centre Hospitalier de Versailles (FR), Hôpital de la Timone (FR), Centre Henri Becquerel, UCLouvain (BE)
Openalex Percentile: Top 4%
Acute Lymphoblastic Leukemia research
5.64
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