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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-06-1744. This Article Full Text (PDF) All Versions of this Article: 2002-06-1744v1 101/5/2049    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ritgen, M. Articles by Dreger, P. Search for Related Content PubMed PubMed Citation Articles by Ritgen, M. Articles by Dreger, P. Social Bookmarking                   What's this? Submitted June 12, 2002 Accepted October 3, 2002 Unmutated immunoglobulin variable heavy chain gene status remains an adverse prognostic factor after autologous stem cell transplantation for chronic lymphocytic leukemia Matthias Ritgen*, Alexandra Lange, Stephan Stilgenbauer, Hartmut Dohner, Christian Bretscher, Heidi Bosse, Ariane Stuhr, Michael Kneba, and Peter Dreger 2nd Department of internal Medicine, University of Kiel, Kiel, Germany 3rd Department of internal Medicine, University of Ulm, Ulm, Germany Department of Hematology, AK St. Georg, Hamburg, Germany * Corresponding author; email: m.ritgen{at}med2.uni-kiel.de. An unmutated germline configuration of the immunoglobulin variable heavy chain gene (VH) has emerged to be a crucial adverse prognostic factor in chronic lymphocytic leukemia (CLL) under conventional treatment. The purpose of the present study was to investigate whether the VH mutational status retains its prognostic value in CLL also in the setting of autologous stem cell transplantation (SCT). Therefore we investigated the mutational status in 58 patients with CLL who underwent myeloablative radiochemotherapy with SCT. Rearranged VH genes were analyzed by multiplex PCR and direct sequencing using FR1 family-specific primers and JH consensus primers. Twenty patients (34%) showed less than 98% homology compared to germline VH sequences and were considered as mutated, whereas 38 patients (66%) had an unmutated VH status (median mutational rate of 0% (0-1.7%)). An unmutated VH configuration was strongly correlated with the presence of short lymphocyte doubling time (p=.003), and high lymphocyte count (p=.005). Time to clinical relapse and time to recurrence of monoclonal B cells as assessed by consensus IgH CDR3 PCR was significantly shorter in the group with unmutated VH genes (2-year probability 19% vs. 0%, p=0.0008, and 34% vs. 9%, p=.0006, respectively). These results show that in CLL, an unmutated VH gene status of the tumor clone remains an adverse prognostic factor after SCT. Nevertheless, the hitherto only three deaths and the median treatment-free interval of 49 months in the unmutated cohort suggest a beneficial effect of SCT for this high-risk population in comparison to conventional treatment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Friedrichs, S. Siegel, M. Kloess, A. Barsoum, J. Coggin Jr., J. Rohrer, I. Jakob, M. Tiemann, K. Heidorn, C. Schulte, et al. 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