Stem cell collection and gene transfer in fanconi anemia

Patrick F. Kelly, Susan Radtke, Cristof von Kalle, Brenden Balcik, Kimberley Bohn, Robin Mueller, Todd Schuesler, Moira Haren, Lilith Reeves, Jose A. Cancelas, Thomas Leemhuis, Richard Harris, Arleen D. Auerbach, Franklin O. Smith, Stella M. Davies, David A. Williams

Research output: Contribution to journalArticle

98 Scopus citations


Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive bone marrow failure (BMF), congenital anomalies, and a predisposition to malignancy. Successful gene transfer into hematopoietic stem cells (HSCs) could reverse BMF in this disease. We developed clinical trials to determine whether a sufficient number of CD34+ stem cells could be collected for gene modification and to evaluate the safety and efficacy of HSC-corrective gene transfer in FA genotype A (FANCA) patients. Here, we report that FA patients have significant depletion of their BM CD34+ cell compartment even before severe pancytopenia is present. However, oncoretroviral-mediated ex vivo gene transfer was efficient in clinical scale in FA-A cells, leading to reversal of the cellular phenotype in a significant percentage of CD34+ cells. Re-infusion of gene-corrected products in two patients was safe and well tolerated and accompanied by transient improvements in hemoglobin and platelet counts. Gene correction was transient, likely owing to the low dose of gene-corrected cells infused. Our early experience shows that stem cell collection is well tolerated in FA patients and suggests that collection be considered as early as possible in patients who are potential candidates for future gene transfer trials.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalMolecular Therapy
Issue number1
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Kelly, P. F., Radtke, S., von Kalle, C., Balcik, B., Bohn, K., Mueller, R., Schuesler, T., Haren, M., Reeves, L., Cancelas, J. A., Leemhuis, T., Harris, R., Auerbach, A. D., Smith, F. O., Davies, S. M., & Williams, D. A. (2007). Stem cell collection and gene transfer in fanconi anemia. Molecular Therapy, 15(1), 211-219.