Originally published as JCO Early Release 10.1200/JCO.2006.06.7165 on September 11 2006

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Detection of Subclinical Systemic Disease in Primary CNS Lymphoma by Polymerase Chain Reaction of the Rearranged Immunoglobulin Heavy-Chain Genes

Kristoph Jahnke, Michael Hummel, Agnieszka Korfel, Thomas Burmeister, Philipp Kiewe, Hermann Ayke Klasen, Hans-Henning Müller, Harald Stein, Eckhard Thiel

From the Departments of Hematology, Oncology, and Transfusion Medicine, and General Pathology and Reference Center for Hematopathology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin; and the Department of Radiation Therapy and Medical Oncology, Pius Hospital Oldenburg, Oldenburg, Germany

Address reprint requests to Kristoph Jahnke, MD, Oregon Health and Science University, Department of Neurology, Blood-Brain Barrier and Neuro-Oncology Program, 3181 SW Sam Jackson Park Rd, L603, Portland, OR 97239-3098; e-mail: kristoph.jahnke{at}charite.de

PURPOSE: To search for subclinical systemic disease in bone marrow and peripheral blood in patients with primary CNS lymphoma (PCNSL) to elucidate whether extracerebral relapse may represent a sequel of initial occult systemic disease rather than true extracerebral spread.

PATIENTS AND METHODS: Bone marrow and peripheral-blood specimens of 24 PCNSL patients were examined using polymerase chain reaction (PCR) for analysis of clonally rearranged immunoglobulin heavy-chain (IgH) genes.

RESULTS: Identical dominant PCR products were found in bone marrow aspirates, blood samples, and tumor biopsy specimens of two patients, indicating that the same tumor cell population is present in the CNS and in extracerebral sites. Follow-up IgH PCR performed in one of these patients in complete remission 24 months after diagnosis yielded a persistent monoclonal product in the blood. An oligoclonal IgH rearrangement pattern was found in the tumor specimen of two other patients, whereas bone marrow and blood samples demonstrated the same dominant PCR products. Follow-up PCR showed a persistent monoclonal amplificate in blood in one of these patients 27 months after diagnosis.

CONCLUSION: It could be demonstrated for the first time that subclinical systemic disease can be present in PCNSL patients at initial diagnosis. Our findings may have an impact on the understanding of PCNSL pathogenesis and the extent of staging and treatment.

published online ahead of print at www.jco.org on September 11, 2006

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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