title: Concomitant systemic and central nervous system non-Hodgkin lymphoma: the role of consolidation in terms of high dose therapy and autologous stem cell transplantation. A 60-case retrospective study from LYSA and the LOC network.
abstract: The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23-85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n = 54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1-5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42 ± 7% and 44 ± 7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P = 0.008) and (P = 0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07-0.67)] and progression-free survival [HR = 0.17 (0.05-0.54)]). In conclusion, non-Hodgkin lymphoma prognosis with concomitant systemic and neurological involvement at diagnosis is poor with a high risk of relapse when treated with conventional chemotherapies alone. This retrospective study supports the feasibility and the potential benefit of a consolidative strategy with high-dose therapy followed by autologous stem cell transplantation in this subset of patients. This strategy and the best intensive chemotherapy regimen remain to be validated in prospective trials.
authors.affiliation: Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire (CHU), Faculté de médecine, Caen, France damaj-gl@chu-caen.fr.
authors.forename: Gandhi
authors.initials: G
authors.lastname: Damaj
authors.affiliation: Hématologie, CHU, Amiens, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ivanoff
authors.affiliation: Hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Coso
authors.affiliation: Hématologie, CHU Purpan, Toulouse, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysaebert
authors.affiliation: Hématologie, Hôpital La Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Choquet
authors.affiliation: Neurologie, Hôpital La Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Houillier
authors.affiliation: Hématologie, CHU, Amiens, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Parcelier
authors.affiliation: Hématologie, Hôpital Général, Meaux, France.
authors.forename: Wajed
authors.initials: W
authors.lastname: Abarah
authors.affiliation: Hématologie, Hôpital St Antoine, AP-HP, Paris, France.
authors.forename: Zora
authors.initials: Z
authors.lastname: Marjanovic
authors.affiliation: Hématologie, CHU, Grenoble, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Gressin
authors.affiliation: Hématologie, Hôpital Général, St Quentin, France.
authors.forename: Reda
authors.initials: R
authors.lastname: Garidi
authors.affiliation: Hématologie, Hôpital Général, St Quentin, France.
authors.forename: Momar
authors.initials: M
authors.lastname: Diouf
authors.affiliation: Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire (CHU), Faculté de médecine, Caen, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Gac
authors.affiliation: Unité d'Hémopathies Lymphoïdes, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Jehan
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire (CHU), Faculté de médecine, Caen, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Troussard
authors.affiliation: Hématologie, CHRU, Lille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauseur
authors.affiliation: Hématologie, Centre Léon Berard, Lyon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Ghesquières
authors.affiliation: Hématologie, Centre René Huguenin-Institut Curie, Saint Cloud, France Collège de France, CNRS UMR 7241/INSERM U1050, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Soussain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019162:Anesthetics, Combined / Q000008:administration & dosage*; D018943:Anthracyclines / Q000008:administration & dosage; D064592:Autografts; D016543:Central Nervous System Neoplasms / Q000401:mortality* / Q000628:therapy*; D060830:Consolidation Chemotherapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate
chemical_list: D019162:Anesthetics, Combined; D018943:Anthracyclines; D008727:Methotrexate