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.

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 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

J Clin Oncol. 2016 Aug 1;34(22):2566-7. doi: 10.1200/JCO.2016.67.4234. PubMed

J Clin Oncol. 2016 Sep 10;34(26):3230. doi: 10.1200/JCO.2016.69.7953. PubMed

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