title: Early response to high-dose methotrexate, vincristine, and procarbazine chemotherapy-adapted strategy for primary CNS lymphoma: no consolidation therapy for patients achieving early complete response.
abstract: Optimal treatment strategies for primary central nervous system lymphoma (PCNSL) have not been established. In this study, we investigated the treatment outcomes and prognostic factors of high-dose methotrexate, vincristine, and procarbazine (MVP) chemotherapy followed by an interim response-adapted intensification strategy in immunocompetent patients with PCNSL. We evaluated the evidence of infection with Epstein-Barr virus (EBV) in both brain tumor tissue and whole blood. Forty patients were retrospectively reviewed. Ten (25 %) patients who achieved complete response (CR) in the interim analysis did not receive any additional consolidation treatment after completion of planned high-dose MVP chemotherapy. Additional radiotherapy (n = 9) or autologous stem cell transplantation (ASCT) (n = 7) was performed in patients who did not achieve CR in the interim analysis. The median age was 55 years. The overall CR rate was 62.5 % (n = 25), and the objective response rate was 75.0 %. Two-year overall survival (OS) was 59.8 %, and 2-year progression-free survival was 47.1 %. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 47.5 and 32.5 % of patients, respectively. Treatment-related mortality was 15.0 % (n = 6), and four patients developed delayed neurotoxicity. There was no evidence of EBV-encoded RNA expression in brain tumor tissue. Ten (29.4 %) of 34 patients showed detectable EBV-DNA in whole blood. Poor performance status and EBV-DNA positivity in whole blood were significantly associated with inferior OS (p = 0.032, p = 0.023, respectively). We suggest that high-dose MVP chemotherapy followed by an early response-adapted intensification strategy may be effective and minimize the number of patients who receive radiotherapy or ASCT in the early course of treatment.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chang
authors.forename: Chang-Ok
authors.initials: CO
authors.lastname: Suh
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yundeok
authors.initials: Y
authors.lastname: Kim
authors.forename: Doh Yu
authors.initials: DY
authors.lastname: Hwang
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Jang
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Hyun
authors.forename: June-Won
authors.initials: JW
authors.lastname: Cheong
authors.forename: Yoo Hong
authors.initials: YH
authors.lastname: Min
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D064592:Autografts; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D004279:DNA, Viral / Q000378:metabolism; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000528:radiation effects; D004854:Herpesvirus 4, Human; D006801:Humans; D008223:Lymphoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D012367:RNA, Viral / Q000378:metabolism; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D011344:Procarbazine; D014750:Vincristine; D008727:Methotrexate