SEARCH:   Advanced

Blood, 15 January 2007, Vol. 109, No. 2, pp. 503-506. Prepublished online as a Blood First Edition Paper on September 14, 2006; DOI 10.1182/blood-2006-06-031476. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-031476v1 109/2/503    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Engel, B. C. Articles by Kohn, D. B. Search for Related Content PubMed PubMed Citation Articles by Engel, B. C. Articles by Kohn, D. B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 27, 2006 Accepted August 29, 2006 Prolonged pancytopenia in a gene therapy patient with ADA-Deficient SCID and Trisomy 8 Mosaicism - a case report Barbara C. Engel, Greg M. Podsakoff, Joanna L. Ireland, E. Monika Smogorzewska, Denise A. Carbonaro, Kathy Wilson, Ami J. Shah, Neena Kapoor, Mirna Sweeney, Mark Borchert, Gay M Crooks, Kenneth I. Weinberg, Robertson Parkman, Howard M. Rosenblatt, Shi-Qi Wu, Michael S. Hershfield, Fabio Candotti, and Donald B. Kohn* Childrens Hospital Lose Angeles, Los Angeles, CA, USA Childrens Hospital Lose Angeles, General Clinical Research Center, Los Angeles, CA, USA Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA Childrens Hospital Lose Angeles, Dept. of Pathology, Los Angeles, CA, USA Duke University Medical Center, Durham, NC, USA National Human Genome Research Institute, NIH, Bethesda, MD, USA * Corresponding author; email: dkohn{at}chla.usc.edu. A subject with adenosine deaminase deficient severe combined immune deficiency (ADA(-) SCID) was enrolled into a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. Following the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan, but then persisted, necessitating administration of untransduced autologous bone marrow back-up at day +40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day +88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pre-treatment marrow sample, which may have caused the lack of hematopoietic reconstitution. The confounding effects of this pre-existing marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy using autologous hematopoietic stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020