TOPIC REVIEW High-dose chemotherapy with hematopoietic stem cell transplantation for the treatment of primary central nervous system lymphoma Christopher J. Campen • Rebecca L. Tombleson • Myke R. Green Received: 7 November 2009 / Accepted: 21 June 2010 Ó Springer Science+Business Media, LLC. 2010 Abstract Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoid neoplasm for which current regimens utilizing standard-dose chemotherapy and/or radiation therapy lead to high relapse rates and/or unacceptable neurologic sequelae. High-dose chemother- apy followed by hematopoietic stem cell transplantation may overcome limitations of current treatment schemas. A search was performed of all English-language literature (1968 to June 2009) within the MEDLINE, EMBASE and Cochrane Library databases to identify relevant clinical trials using the terms stem cell transplantation, bone marrow transplantation, primary central nervous system lymphoma, and PCNSL. Bibliographies were reviewed to extract other relevant articles. Use of high-dose chemo- therapy followed by hematopoietic stem cell transplanta- tion for the treatment of PCNSL in a predominantly elderly population is feasible. Use of this treatment modality for newly diagnosed and recurrent or relapsed disease is bur- dened by a paucity of data guiding patient selection, opti- mal induction regimen, stem cell mobilization and conditioning chemotherapy. Data are also sparse and con- founding regarding timing of initiation of this procedure relative to the natural history of the disease and timing of each chemotherapy regimen relative to each other. High- dose chemotherapy followed by hematopoietic stem cell transplantation remains an experimental procedure with insufficient data to guide clinicians. However, the data are encouraging and merit continued research to guide patient selection and treatment regimens which may produce optimal outcomes. Keywords Stem cell transplantation Á Dose intensity Á Primary CNS lymphoma Á PCNSL Á High dose chemotherapy Introduction Primary central nervous system lymphoma (PCNSL) is an invariably unique and aggressive hematologic malignancy, occurring in both immunocompromised and immunocom- petent hosts. By definition, PCNSL is an uncommon variant of extranodal non-Hodgkin’s lymphoma (NHL) that is confined to the central nervous system (CNS) and typically presents as an intracerebral mass. However, PCNSL may also arise within the ocular cavity or elsewhere within the neuraxis. Although PCNSL is morphologically and phe- notypically similar to non-Hodgkin’s lymphoma, disease- specific attributes confound investigators from elucidating the optimal therapeutic approach to this rare disease. Prognosis and outcome from standard therapy has improved recently, but further gains in outcomes are needed [1–4]. Owing to the blood–brain barrier (BBB), PCNSL occurs within an immunologically privileged site of the body rendering targeted therapies that have dramatically changed outcomes in NHL less effective. In addition, the ther- apies that have yielded clinical benefit in PCNSL, such as C. J. Campen Á M. R. Green Department of Pharmacy, University Medical Center, Tucson, AZ, USA C. J. Campen Á M. R. Green (&) Department of Hematology and Medical Oncology, Arizona Cancer Center/University Medical Center, P.O. Box 245009, 1501 N. Campbell Ave, Tucson, AZ 85724-5009, USA e-mail: mgreen@umcaz.edu R. L. Tombleson Department of Oncological Sciences, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., MCC- Pharm, Tampa, FL 33612, USA 123 J Neurooncol DOI 10.1007/s11060-010-0279-5