Relapse of Central Nervous System Lymphoma after systemic Lymphoma (SCNSL): Clinical Features and Outcome as compared to Primary CNS Lymphoma (PCNSL) Patients
Authors: Schmidt-Wolf Ingo , Pels Hendrik , Jürgens Annika , Patrij Katrin , Wätzel Luise , Herrlinger Ulrich , Schulz Holger , Engert Andreas , Linnebank Michael , Schackert Gabriele , Reichmann Heinz , Kroschinsky Frank , Vogt-Schaden Marlies , Egerer Gertlinde , Schaller Carlo , Lamprecht Monika , Hau Peter , Deckert Martina , Fimmers Rolf , Bangard Christoph , Reiser Marcel 
Published: October 2019

Abstract
Background: Data on relapsed central nervous system lymphoma (CNSL) is limited. Therefore, we have evaluated the clinical characteristics and outcome of relapsed CNSL patients at our centers. A central nervous system relapse is a serious complication of aggressive lymphomas. The prognosis is generally regarded as poor and standard therapies of relapsed CNSL have not yet been established.
Patients and Methods: All pts with primary and secondary CNSL who were treated at Bonn University Hospital and Cologne University Hospital from 09/1995 – 12/2007 were included into the study. 125 pts could be identified; 102 with newly diagnosed primary CNSL (PCNSL) and 23 pts with secondary CNSL (SCNSL). First-line- treatment for pts with PCNSL consisted of high-dose methotrexate (MTX) in combination with vincristine, ifosfamide, prednisolone and cytarabine (Bonn protocol). Patients with SCNSL received a CHOP-like combination chemotherapy first-line. At cerebral relapse, for 17/23 pts SCNSL-treatment was Bonn polychemotherapy, 4/23 pts received an acute leukaemia regimen (GMALL-B-ALL protocol) at relapse and 2/23 received radiotherapy only. 81/125 pts (64%) were male with a median age of 62 yrs (range 27–77) and 72/125 pts (57%) were older > 60 years.
Results: Overall response rate (CR+PR) was 63% (49CR +19PR) for PCNSL and 65% (12CR+3PR) for SCNSL. Median overall survival was 15.8 months for all 125 pts and 23 vs. 7.1 months for PCNSL and SCNSL. There was a difference in OS of 15 months between pts >60 yrs (median 13 months) vs. pts <60 yrs (median 28 months). After a median follow-up of 12 months (range 1–119) 80/125 (64%) pts with PCNSL and SCNSL relapsed (37) or progressed (43). All 80 patients relapsed/progressed again within the CNS. 65/80 pts initially suffered from PCNSL, 15/80 pts from SCNSL. Prognosis of relapsed/progressed PCNSL and SCNSL was dismal. 56/80 patients died. Median OS was short with only 8.5 months (range 1–124) survival time after relapse. Treatment at relapse was radiotherapy alone (16), radiotherapy in combination with temozolomide (2), radiotherapy in combination with MTX, dexamethasone and cytarabine (1), PVC-Chemotherapy (1), BEAM-Polychemothapy (1), Bonn polychemotherapy (7), cytarabine and etoposide (CYVE) with autologous stem cell transplantation (5) and “wait and see” (4). Response to relapse treatment was in 12 cases CR, in 9 cases PR and in 16 cases PD. Treatment at progress was radiotherapy alone (16), radiotherapy in combination with temozolomide (3), radiotherapy in combination with MTX, dexamethasone and cytarabine (1), BEAM-polychemotherapy (1), Bonn polychemotherapy (1), cytarabine and etoposide (CYVE) with autologous stem cell transplantation (2) and “wait and see”/no therapy (16). Response to progress treatment was in 3 cases CR, in 3 cases PR and in 37 cases PD.
Conclusions: HD-MTX chemotherapy according to the Bonn Protocol is equally effective in PCNSL and SCNSL pts although the prognosis of pts with SCNSL seems to be worse. Prognosis of relapsed and refractory CNSL pts is dismal. Median OS was only 8.5 months. Therefore, new treatment strategies are urgently needed.