Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Engel, BC; Podsakoff, GM; Ireland, JL; Smogorzewska, EM; Carbonaro, DA; Wilson, K; Shah, A; Kapoor, N; Sweeney, M; Borchert, M; Crooks, GM; Weinberg, KI; Parkman, R; Rosenblatt, HM; Wu, S-Q; Hershfield, MS; Candotti, F; Kohn, DB

Published Date

  • January 15, 2007

Published In

Volume / Issue

  • 109 / 2

Start / End Page

  • 503 - 506

PubMed ID

  • 16973956

Pubmed Central ID

  • PMC1785101

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2006-06-031476


  • eng

Conference Location

  • United States