PROGNOSTIC FACTORS, MANAGEMENT AND OUTCOME OF AN INTERNATIONAL SERIES OF 41 PATIENTS WITH PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA (PMLBCL) AND CENTRAL NERVOUS SYSTEM (CNS) INVOLVEMENT

Introduction: CNS dissemination is an uncommon event in PMLBCL. International cooperation is an important tool to improve our knowledge on this poorly-investigated condition. Methods: Data from PMLBCL pts with CNS disease at presentation or relapse treated at 24 Centers from 6 countries were analyzed. Results: 41 pts (median age 32, range 14-52; 22 males) were considered. At initial lymphoma diagnosis, 20 (49%) had advanced stage, 21 (51%) B symptoms, 39 (95%) bulky disease, 37 (90%) raised LDH, 18 (44%) had extranodal disease (16 in abdomen), 26 (63%) had an aaIPI ≥2. First-line treatment was CHOP14/21 in 20 pts, daEPOCH in 6, M/VACOP-B in 15, combined with rituximab in 39 (95%), and followed by mediastinal irradiation in 14. CNS prophylaxis was administered in 6 pts. CNS involvement was recorded at initial diagnosis in one (2%) pt, at first relapse in 34 (83%), at 3rd-4th relapse in 6 (15%), with a median time to CNS relapse of 7 (0-24) months. CNS was the only site of recurrence in 24 (59%) pts, all at first relapse. Brain or cerebellum were involved in 38 (93%) pts, associated with meningeal infiltration in 6 of them, spinal cord in 1; meninges were the exclusive site of disease in 2 (5%) pts. Treatment was followed by complete remission in 13 pts (32%; 95%CI = 18-46), all of them were treated at presentation or first relapse, and, with a single exception, received high-dose-methotrexate (HD-MTX)-based therapy plus ASCT ± WBRT (Table). Twenty-four treated pts experienced further tumor failure, invariably in the CNS, with concomitant systemic disease in 8; 10 pts with progressive disease limited to the CNS received WBRT, combined with ASCT and/or other drugs, 8 achieving a CR lasting 16-84 months (Table). Pts with CNS involvement at 3rd-4threlapse also had systemic, uncontrolled disease, and did not benefit from treatment. At a median follow-up of 61 (10-173) months, 9 pts remain relapse-free, with a 5-yr PFS after CNS relapse of 21±6%, and 17 pts are alive, with a 5-yr survival after CNS relapse of 42±8%. Systemic disease and meningeal infiltration were not associated with outcome. The 5-yr survival after CNS relapse of the 26 pts treated with HD-MTX-based combinations was 52±10%. Conclusions: Advanced stage, abdominal extranodal disease and high LDH levels are often recorded in PMLBCL pts with CNS recurrence. Unlike other aggressive lymphomas, CNS involvement at presentation and meningeal infiltration are rare in PMLBCL. Prognosis is poor, but HD-MTX-based therapy and consolidative ASCT are associated with encouraging results. WBRT contributes to the achievement of long-lasting remission even in pts with chemorefractory disease. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Lymphoid Cancers - Other No conflicts of interest pertinent to the abstract.