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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 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 Citation Map 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 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. Related Collections Hematopoiesis and Stem Cells Brief Reports Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Brief report Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report Barbara C. Engel1,, Greg M. Podsakoff1,, Joanna L. Ireland1, E. Monika Smogorzewska1, Denise A. Carbonaro1, Kathy Wilson1, Ami Shah1, Neena Kapoor1, Mirna Sweeney2, Mark Borchert1, Gay M. Crooks1, Kenneth I. Weinberg1, Robertson Parkman1, Howard M. Rosenblatt3, Shi-Qi Wu4, Michael S. Hershfield5, Fabio Candotti6, and Donald B. Kohn1, 1 Division of Research Immunology/Bone Marrow Transplantation, 2 General Clinical Research Center, and 4 Department of Pathology, Childrens Hospital Los Angeles, CA; 3 Texas Children's Hospital, Baylor College of Medicine, Houston; 5 Duke University Medical Center, Durham, NC; 6 National Human Genome Research Institute, National Institutes of Health, Bethesda, MD A patient with adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After 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 the 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 pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. B. Gaspar, A. Aiuti, F. Porta, F. Candotti, M. S. Hershfield, and L. D. Notarangelo How I treat ADA deficiency Blood, October 22, 2009; 114(17): 3524 - 3532. [Abstract] [Full Text] [PDF] A. Aiuti, F. Cattaneo, S. Galimberti, U. Benninghoff, B. Cassani, L. Callegaro, S. Scaramuzza, G. Andolfi, M. Mirolo, I. Brigida, et al. Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency N. Engl. J. Med., January 29, 2009; 360(5): 447 - 458. [Abstract] [Full Text] [PDF] W. Qasim, H Bobby Gaspar, and A. J Thrasher Update on clinical gene therapy in childhood Arch. Dis. Child., November 1, 2007; 92(11): 1028 - 1031. [Abstract] [Full Text] [PDF]

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