Novel Lineage Depletion Preserves Autologous Blood Stem Cells For Gene Therapy Of Fanconi Anemia Complementation Group A
EHA Learning Center. Adair J. Nov 1, 2018; 234397
Topic: 1B Bone marrow failure
Jennifer E. Adair
Jennifer E. Adair
Login now to access Regular content available to all registered users.

Access to EHA Members only content is an EHA membership benefit.
Click here to join EHA or renew your membership here.

Journal Abstract
Discussion Forum (0)
Rate & Comment (0)

Co-Authors: Devikha Chandrasekaran, Gabriella Sghia-Hughes, Kevin G. Haworth, Ann E. Woolfrey, Lauri M. Burroughs, Grace Y. Choi, Pamela S. Becker, Hans-Peter Kiem

Abstract: A hallmark of Fanconi anemia is accelerated decline in hematopoietic stem and progenitor cells (CD34 +) leading to bone marrow failure. Long-term treatment requires hematopoietic cell transplantation from an unaffected donor but is associated with potentially severe side-effects. Gene therapy to correct the genetic defect in the patient’s own CD34+ cells has been limited by low CD34+ cell numbers and viability. Here we demonstrate an altered ratio of CD34Hi to CD34Lo cells in Fanconi patients relative to healthy donors, with exclusive in vitro repopulating ability in only CD34Hi cells, underscoring a need for novel strategies to preserve limited CD34+ cells. To address this need, we developed a clinical protocol to deplete lineage+(CD3+, CD14+, CD16+ and CD19+) cells from blood and marrow products. This process depletes >90% of lineage+cells while retaining ≥60% of the initial CD34+cell fraction, reduces total nucleated cells by 1–2 logs, and maintains transduction efficiency and cell viability following gene transfer. Importantly, transduced lineage− cell products engrafted equivalently to that of purified CD34+ cells from the same donor when xenotransplanted at matched CD34+ cell doses. This novel selection strategy has been approved by the regulatory agencies in a gene therapy study for Fanconi anemia patients (NCI Clinical Trial Reporting Program Registry ID NCI-2011-00202; identifier: 01331018).

Article Number: 1806

Doi: 10.3324/haematol.2018.194571

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.

Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.

Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.

Save Settings