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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.
AuthorsYu Ri Kim, Se Hoon Kim, Jong Hee Chang, Chang-Ok Suh, Soo-Jeong Kim, Yundeok Kim, Doh Yu Hwang, Ji Eun Jang, Shin Young Hyun, June-Won Cheong, Yoo Hong Min, Jin Seok Kim
JournalAnnals of hematology (Ann Hematol) Vol. 93 Issue 2 Pg. 211-9 (Feb 2014) ISSN: 1432-0584 [Electronic] Germany
PMID23903866 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA, Viral
  • RNA, Viral
  • Procarbazine
  • Vincristine
  • Methotrexate
Topics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
  • Autografts
  • Brain Neoplasms (metabolism, mortality, pathology, therapy, virology)
  • DNA, Viral (metabolism)
  • Disease-Free Survival
  • Epstein-Barr Virus Infections (metabolism, mortality, pathology, therapy)
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic (drug effects, radiation effects)
  • Gene Expression Regulation, Viral (drug effects, radiation effects)
  • Herpesvirus 4, Human
  • Humans
  • Lymphoma (metabolism, mortality, pathology, therapy, virology)
  • Male
  • Methotrexate (administration & dosage, adverse effects)
  • Middle Aged
  • Procarbazine (administration & dosage, adverse effects)
  • RNA, Viral (metabolism)
  • Retrospective Studies
  • Stem Cell Transplantation
  • Survival Rate
  • Vincristine (administration & dosage, adverse effects)

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