High Dose and Conventional Anthracycline Regimen for Adult Non-Hodgkin’s Primary Bone Lymphoma (PBL). A GOELAMS’s Trial.
Authors: Schmidt-Tanguy Aline , Desablens Bernard , Lamy Thierry , Bernard Marc , Senecal Delphine , Abgrall Jean-Francois , Casassus Philippe , Dugay Jacqueline , Rodon Philippe , Hunault-Berger Mathilde , Ifrah Norbert ,   the GOELAMS Group, Colombat Philippe 
Published: October 2019

Abstract
Between March 1986 and May 1998, 28 patients (pts) (60,7% M, 39.3% F) with localized high-grade PBL were enrolled in the 02 (< 60 years, 20 pts) or 03 (≥ 60 years, 8 pts) GOELAMS trial. The aim of the study was to evaluate the OS, DFS and FFR after 3 VCAP courses (eldisine 3 mg/m² d1, doxorubicin 60 mg/m² d1, cyclophosphamide 1500 mg/m² d1, prednisone 80 mg/m² d1–5 every 3 weeks) in younger pts and after 3 VCEP-Bleo courses (eldisine 3 mg/m² d1, cyclophosphamide 750 mg/m² d2, farmorubicin 80 mg/m² d1, prednisone 50 mg/m²/d d1–7, bleomycine 10 mg d1 and 5, every 3 weeks) in older pts. Involved field radiotherapy (40 Gy) was performed for every patient. The median age was 46 years (17–69) and 70 years (65–75) respectively. Four patients between 60 and 69 with a good performance status (PS) were included in the 02 trial. In contrary to previous reports, the main localization were axial skeleton (20, 71%) including vertebrae (13), pelvis (5) and ribs (2) while skull and extremities were involved in both 4 patients (mandible 3, occiput 1, tibia 1, finger 1, humerus 2, one of them with including scapula involvement). Histological subtype included diffuse large cell lymphoma (68%), diffuse mixed cell lymphoma (14%), immunoblastic (10%), anaplastic Ki1+ (3%) and unclassified (3%). Immunophenotype were B (53.6%), T (3.6%), anaplastic (3.6%) or undone (39.3%). Ann Arbor classification included 23 stage I (82%) and 5 stage 2 (18%). Skin and subcutaneous tissues were involved by extension in 2 pts. Spinal compression, epidural involvement and paraplegia were observed in 8 pts. B symptoms were present in 5 pts (including 2 stage I). LDH were elevated in 5/23 pts. The IPI score was 0 for 18%, 1 for 39%, 2 for 14%, 3 for 10% and undetermined for 18%. PS >2 and bulk (≥ 5 cms) were observed in 43% and 39% of pts respectively. Besides age, VCAP and VCEP-Bleo groups were comparable for histological type, localization, Ann Arbor classification, B symptoms and LDH. All but one patient (96%) achieved CR. A 63 years old patient with costal localization, resistant to chemotherapy, died of progression after 15 months. Relapses occurred in 9/27 pts (33%, 3/8 for older pts, 6/20 for younger pts) at a median time of 2.3 years (0.4–6.5) from CR. Four of these relapses occurred before 2 years of CR, 4 between 2.1 and 5 years and 1 occurred 6.5 years after CR. Amongst 8 pts with spinal compression, 1 died in CR, 4 relapsed (1 alive in CR2) and 3 are in continuous CR. The relapse rate of pts without epidural involvement was 25% (5/20). With a median follow up of 8 years (1.2–17), OS, EFS and FFR were 62% (±12), 56% (±10) and 60% (±10), respectively. OS, EFS and FFR were 66%, 54%, 63% and 56%, 62%, 62% in VACP group and VCEP-Bleo group respectively. In univariate analysis, PS >2 significantly decreases OS, EFS and FFR (P = .036, .013 and .064). Epidural extension significantly decreases EFS (P = .009) but not OS. In multivariate analysis, poor PS but not epidural extension significantly decrease EFS and OS (P=.02 and P = .03 respectively for PS). The survival results of PBL are very similar to survival of 325 localized aggressive NHL treated in the 02-GOELAMS trial reported previously (Desablens ASH 2002). The poor prognostic value of PS and epidural extension of PBL should be underlined.