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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2210. This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hamblin, T. Search for Related Content PubMed Articles by Hamblin, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Comment on Ritgen et al, page 2600 CLL: to mend it or be rid of it Terry Hamblin UNIVERSITY OF SOUTHAMPTON Chronic lymphocytic leukemia with unmutated IgVH genes can be suppressed by the immunologic effects of stem cell allograft. Chronic lymphocytic leukemia (CLL) is generally considered treatable but ultimately incurable even by high-dose chemotherapy. Because most patients are elderly, conventional stem cell allografting is too hazardous for all but a few. In this issue, Ritgen and colleagues raise the hope that the immunologic effect of allograft with reduced-intensity conditioning may sufficiently suppress the disease to make cure a possibility. CLL comes in 2 forms: the first, with mutated immunoglobulin variable region (IgVH) genes, is usually benign with an average survival of 25 years; the second, with unmutated IgVH genes, is usually lethal with a median survival of 8 years.1,2 Abnormalities of the p53 pathway (chromosomal deletions at 17p13 or 11q23) make things worse.3 Patients with 17p13 deletions survive for only 3 years on average. A previous study by the German group4 demonstrated that high-dose chemo-radiotherapy followed by autologous stem cell rescue produced long-lasting, complete remissions in CLL with mutated IgVH genes. Furthermore, elimination of minimal residual disease (MRD), detectable by a sensitive IgH real-time polymerase chain reaction (PCR) assay, was achieved in all and maintained in most patients. On the other hand, in patients with unmutated IgVH genes treated in this way, complete remissions lasted on average only 3 years and reappearance of MRD was inevitable by 4 years. The new study of 9 patients receiving a stem cell allograft after reduced-intensity conditioning demonstrates that control of MRD in patients with unmutated IgVH genes can be achieved by the immunologic effects of the grafted stem cells. In 5 patients, the disappearance of MRD appeared to be a consequence of the development of graft-versus-host disease. Two of the remaining patients became MRD negative after donor lymphocyte infusion (DLI). One patient remained in remission without eliminating MRD despite DLI, and one patient died from progressive disease despite DLI. This last patient was the only one with a chromosome deletion at 17p13, implicating p53 malfunction. MRD kinetics after autologous stem cell transplantation (SCT) and nonmyeloablative allogeneic SCT. See the complete figure in the article beginning on page 2600.   Stem cell allograft with reduced-intensity conditioning can be performed well into the age range when CLL becomes common. This paper encourages us to enter more patients into clinical trials to evaluate this treatment. However, the prospect for patients with p53 abnormalities remains dismal, and this problem remains the focus for intensive research. References Damle RN, Wasil T, Fais F, et al. IgV gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94: 1840-1847.[Abstract/Free Full Text] Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94: 1848-1854.[Abstract/Free Full Text] Krober A, Seiler T, Benner A, et al. VH mutational status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood. 2002;100: 1410-1416.[Abstract/Free Full Text] Ritgen M, Lange A, Stilgenbauer S, et al. Unmutated immunoglobulin variable heavy-chain gene status remains an adverse prognostic factor after autologous stem cell transplantation for chronic lymphocytic leukemia. Blood. 2003;101: 2049-2053.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR Matthias Ritgen, Stephan Stilgenbauer, Nils von Neuhoff, Andreas Humpe, Monika Brüggemann, Christiane Pott, Thorsten Raff, Alexander Kröber, Donald Bunjes, Richard Schlenk, Norbert Schmitz, Hartmut Döhner, Michael Kneba, and Peter Dreger Blood 2004 104: 2600-2602. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hamblin, T. Search for Related Content PubMed Articles by Hamblin, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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