Stéphane Lepretre1, Aurore Touzart2, Thomas Vermeulin2, Jean-Michel Picquenot2, Aline Tanguy-Schmidt2, Gilles Salles2, Thierry Lamy2, Marie-Christine Béné2, Emmanuel Raffoux2, Françoise Huguet2, Patrice Chevallier2, Serge Bologna2, Réda Bouabdallah2, Jacques Benichou2, Josette Brière2, Anne Moreau2, Valérie Tallon-Simon2, Stéphanie Seris2, Carlos Graux2, Vahid Asnafi2, Norbert Ifrah2, Elizabeth Macintyre2, Hervé Dombret2. 1. Stéphane Lepretre, Valérie Tallon-Simon, and Stéphanie Seris, Institut National de la Santé et de la Recherche Médicale (INSERM) U918, University of Rouen, Centre de Lutte contre le Cancer de Haute-Normandie (CLCC) H. Becquerel; Thomas Vermeulin and Jacques Benichou, Centre Hospitalier Universitaire (CHU) Charles Nicolle and INSERM U657, University of Rouen; Jean-Michel Picquenot, CLCC H. Becquerel, Rouen; Aurore Touzart, Vahid Asnafi, and Elizabeth Macintyre, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, INSERM U1151, and Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades; Emmanuel Raffoux and Hervé Dombret, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot; Josette Brière, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris; Aline Tanguy-Schmidt and Norbert Ifrah, Maladies du sang CHU Angers, INSERM U892, and University of Angers, Angers; Gilles Salles, CHU Centre Hospitalier Lyon-Sud, Pierre Bénite; Thierry Lamy, CHU Ponchaillou, Rennes; Anne Moreau, Marie-Christine Béné, and Patrice Chevallier, CHU Hôtel-Dieu, Nantes; Françoise Huguet, CHU Purpan, Toulouse; Serge Bologna, CHU Vandoeuvre-les-Nancy, Vandoeuvre-les-Nancy; Réda Bouabdallah, CLCC P. Calmette, Marseille, France; and Carlos Graux, Godinne University Hospital, Yvoir, Belgium. stephane.lepretre@chb.unicancer.fr. 2. Stéphane Lepretre, Valérie Tallon-Simon, and Stéphanie Seris, Institut National de la Santé et de la Recherche Médicale (INSERM) U918, University of Rouen, Centre de Lutte contre le Cancer de Haute-Normandie (CLCC) H. Becquerel; Thomas Vermeulin and Jacques Benichou, Centre Hospitalier Universitaire (CHU) Charles Nicolle and INSERM U657, University of Rouen; Jean-Michel Picquenot, CLCC H. Becquerel, Rouen; Aurore Touzart, Vahid Asnafi, and Elizabeth Macintyre, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, INSERM U1151, and Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades; Emmanuel Raffoux and Hervé Dombret, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot; Josette Brière, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris; Aline Tanguy-Schmidt and Norbert Ifrah, Maladies du sang CHU Angers, INSERM U892, and University of Angers, Angers; Gilles Salles, CHU Centre Hospitalier Lyon-Sud, Pierre Bénite; Thierry Lamy, CHU Ponchaillou, Rennes; Anne Moreau, Marie-Christine Béné, and Patrice Chevallier, CHU Hôtel-Dieu, Nantes; Françoise Huguet, CHU Purpan, Toulouse; Serge Bologna, CHU Vandoeuvre-les-Nancy, Vandoeuvre-les-Nancy; Réda Bouabdallah, CLCC P. Calmette, Marseille, France; and Carlos Graux, Godinne University Hospital, Yvoir, Belgium.
Abstract
PURPOSE: This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). PATIENTS AND METHODS: This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. RESULTS: The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. CONCLUSION: In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.
PURPOSE: This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). PATIENTS AND METHODS: This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. RESULTS: The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. CONCLUSION: In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.