Clémentine Sarkozy1, Marek Trneny1, Luc Xerri1, Nick Wickham1, Pierre Feugier1, Sirpa Leppa1, Pauline Brice1, Pierre Soubeyran1, Maria Gomes Da Silva1, Christiane Mounier1, Fritz Offner1, Jehan Dupuis1, Dolores Caballero1, Danielle Canioni1, Marlton Paula1, Richard Delarue1, Pierre Zachee1, John Seymour1, Gilles Salles2, Hervé Tilly1. 1. Clémentine Sarkozy and Gilles Salles, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie, Pierre Bénite and Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux Pierre Bénite; Luc Xerri, Aix-Marseille University and Institut Paoli-Calmettes, Marseille; Pierre Feugier, Centre Hospitalier Universitaire de Nancy and INSERM 954 Université de Lorraine, Nancy; Pauline Brice, Hôpital Saint Louis APHP and Université Paris VII; Danielle Canioni, Assistance Publique Hôpitaux de Paris (APHP) Hôpital Universitaire Necker-Enfants Malades; Richard Delarue, APHP Hôpital Universitaire Necker-Enfants Malades and Descartes-Sorbonne Paris Cité University, Paris; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux, Bordeaux; Christiane Mounier, Institut de Cancérologie Lucien Neuwirth, Saint Priest; Jehan Dupuis, Henri Mondor University Hospital, Créteil; Hervé Tilly, Université de Rouen, Rouen, France; Marek Trneny, Charles University General Hospital, Prague, Czech Republic; Nick Wickham, University of Adelaide, Adelaide; Marlton Paula, Princess Alexandra Hospital, University of Queensland School of Medicine, Brisbane; John Seymour, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia; Sirpa Leppa, Helsinki University Hospital Cancer Center and University of Helsinki, Helsinki, Finland; Maria Gomes Da Silva, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal; Fritz Offner, Gent University, Gent; Pierre Zachee, ZNA Stuivenberg, Antwerp, Belgium; and Dolores Caballero, Universitario de Salamanca, Salamanca, Spain. 2. Clémentine Sarkozy and Gilles Salles, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie, Pierre Bénite and Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux Pierre Bénite; Luc Xerri, Aix-Marseille University and Institut Paoli-Calmettes, Marseille; Pierre Feugier, Centre Hospitalier Universitaire de Nancy and INSERM 954 Université de Lorraine, Nancy; Pauline Brice, Hôpital Saint Louis APHP and Université Paris VII; Danielle Canioni, Assistance Publique Hôpitaux de Paris (APHP) Hôpital Universitaire Necker-Enfants Malades; Richard Delarue, APHP Hôpital Universitaire Necker-Enfants Malades and Descartes-Sorbonne Paris Cité University, Paris; Pierre Soubeyran, Institut Bergonié and Université Victor Segalen Bordeaux, Bordeaux; Christiane Mounier, Institut de Cancérologie Lucien Neuwirth, Saint Priest; Jehan Dupuis, Henri Mondor University Hospital, Créteil; Hervé Tilly, Université de Rouen, Rouen, France; Marek Trneny, Charles University General Hospital, Prague, Czech Republic; Nick Wickham, University of Adelaide, Adelaide; Marlton Paula, Princess Alexandra Hospital, University of Queensland School of Medicine, Brisbane; John Seymour, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia; Sirpa Leppa, Helsinki University Hospital Cancer Center and University of Helsinki, Helsinki, Finland; Maria Gomes Da Silva, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal; Fritz Offner, Gent University, Gent; Pierre Zachee, ZNA Stuivenberg, Antwerp, Belgium; and Dolores Caballero, Universitario de Salamanca, Salamanca, Spain. gilles.salles@chu-lyon.fr.
Abstract
PURPOSE: To study the outcome of histologic transformation (HT) in a large prospective cohort of patients with follicular lymphoma (FL) who previously responded toimmunochemotherapy. PATIENTS AND METHODS: After a median 6-year follow-up of 1,018 randomly assigned patients from the PRIMA trial, disease progression was observed in 463 patients, 194 of whom had histologic documentation. RESULTS: Forty patients had histology consistent with HT, and 154 had untransformed FL (median time to recurrence, 9.6 v 22.8 months, respectively; P = .018). Thirty-seven percent of biopsies performed during the first year of follow-up showed HT corresponding to 58% of all HTs. Altered performance status, anemia, high lactate dehydrogenase level, "B" symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis were identified as HT risk factors. Response (complete v partial) to immunochemotherapy or rituximab maintenance had no impact on the risk of HT. After salvage treatment, patients with HT had less frequent complete response (50.3% v 67.4%; P = .03) and more disease progression (28.2% v 9.6%; P < .001) than patients without HT. Estimated overall survival for the patients with HT was poorer (median, 3.8 v 6.4 years; hazard ratio, 3.9; 95% CI, 2.2 to 6.9). Autologous stem cell transplantation improved the outcomes of patients with HT (median overall survival, not reached v 1.7 years) but not of patients with persistent FL histology. CONCLUSION: HT in patients with FL who previously responded to immunochemotherapy is an early event associated with a poor outcome that may deserve intensive salvage with autologous stem cell transplantation. These data emphasize the necessity for biopsy at the first recurrence of FL.
RCT Entities:
PURPOSE: To study the outcome of histologic transformation (HT) in a large prospective cohort of patients with follicular lymphoma (FL) who previously responded to immunochemotherapy. PATIENTS AND METHODS: After a median 6-year follow-up of 1,018 randomly assigned patients from the PRIMA trial, disease progression was observed in 463 patients, 194 of whom had histologic documentation. RESULTS: Forty patients had histology consistent with HT, and 154 had untransformed FL (median time to recurrence, 9.6 v 22.8 months, respectively; P = .018). Thirty-seven percent of biopsies performed during the first year of follow-up showed HT corresponding to 58% of all HTs. Altered performance status, anemia, high lactate dehydrogenase level, "B" symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis were identified as HT risk factors. Response (complete v partial) to immunochemotherapy or rituximab maintenance had no impact on the risk of HT. After salvage treatment, patients with HT had less frequent complete response (50.3% v 67.4%; P = .03) and more disease progression (28.2% v 9.6%; P < .001) than patients without HT. Estimated overall survival for the patients with HT was poorer (median, 3.8 v 6.4 years; hazard ratio, 3.9; 95% CI, 2.2 to 6.9). Autologous stem cell transplantation improved the outcomes of patients with HT (median overall survival, not reached v 1.7 years) but not of patients with persistent FL histology. CONCLUSION:HT in patients with FL who previously responded to immunochemotherapy is an early event associated with a poor outcome that may deserve intensive salvage with autologous stem cell transplantation. These data emphasize the necessity for biopsy at the first recurrence of FL.
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