Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma The prognosis of immunocompetent patients diag- nosed with primary central nervous system lym- phoma (PCNSL) has improved during the last decade with the introduction of methotrexate (MTX)-based regimens and cranial radiotherapy (RT). With this approach, the median actuarial survival is around 3 yr and 30–40% of patients can be cured (1–3). However, 10–35% of the patients are primarily refractory to these regimens and up to 60% of complete responders eventually relapse during the follow-up (4, 5). The outcome of primarily refractory patients is particularly dismal, with a median survival of <6 months. The infor- mation on salvage therapies in patients who relapse Arellano-Rodrigo E, Lo´pez-Guillermo A, Bessell EM, Nomdedeu B, Montserrat E, Graus F. Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma. Eur J Haematol 2003: 70: 219–224. Ó Blackwell Munksgaard 2003. Abstract: Background: Survival of patients with primary central ner- vous system lymphoma (PCNSL) has improved with methotrexate- based combination regimens and radiotherapy (RT). However, the prognosis of patients who fail or relapse after initial response is poor. Very little data is available on salvage treatment at recurrence. Patients and methods: Sixteen immunocompetent patients (13 males/three females, median age 54 yr) with refractory (one patient) or recurrent (15 patients) PCNSL, homogeneously treated at diagnosis with the cyclo- phorphamide, doxorubicin, Vimcritime, dexamethasome/carmuntime, Uimcritime, cytarabine and methotrexate (CHOD/BVAM) and RT regimen, received etoposide (VP-16), ifosfamide and cytarabine (Ara-C) (VIA) chemotherapy as a salvage treatment. VIA included etoposide 100 mg/m 2 /d days 1–3, ifosfamide 1000 mg/m 2 /d days 1–5, and cyt- arabine 2000 mg/m 2 /12 h day 1. The therapy was repeated every 28 d for a total of planned six cycles. Results: Median time between first complete response (CR) and relapse was 19 months (range: 6– 46 months). Thirteen patients (81%) had a performance status £ 2, six had multifocal PCNSL and six (of eight tested) positive cerebrospinal fluid cytology. The median number of courses per patient was four (range: 1–6). Five patients completed the whole VIA therapy. Six pa- tients (37%) achieved CR. After a median follow-up of 15 months for surviving patients, two have relapsed, with a median failure-free survival of 5 months. Twelve patients have died from progression of PCNSL, with a 12-month overall survival of 41% [95% confidence interval (CI): 16–66]. The major toxicity was World Health Organization grade 2–4 neutropenia (69% of patients) and thrombocytopenia (50%). Five pa- tients had grade 3–4 infectious complications. Finally, one patient de- veloped a severe but reversible ifosfamide encephalopathy. Conclusion: The data presented show that the chemotherapy VIA is an effective salvage regimen for patients with recurrent PCNSL. Eduardo Arellano-Rodrigo 1 , Armando López-Guillermo 1 , Eric M. Bessell 2 , Benet Nomdedeu 1 , Emili Montserrat 1 , Francesc Graus 3 1 Service of Hematology, Institut de Recerca Biomdica August Pi i Sunyer, Hospital Clínic, Barcelona, Spain; 2 Department of Clinical Oncology, Nottingham City Hospital, Nottingham, UK; 3 Service of Neurology, Institut de Recerca Biomdica August Pi i Sunyer, Hospital Clínic, Barcelona, Spain Key words: primary CNS lymphoma; salvage chemotherapy; VIA Correspondence to: Armando López-Guillermo, MD, Department of Hematology, Hospital Clínic, Villarroel, 170, Barcelona 08036, Spain Tel: +34-93-2275414 Fax: +34-93-2275783 e-mail: alopezg@clinic.ub.es Accepted for publication 16 January 2003 Eur J Haematol 2003: 70: 219–224 Printed in UK. All rights reserved Copyright Ó Blackwell Munksgaard 2003 EUROPEAN JOURNAL OF HAEMATOLOGY ISSN 0902-4441 219