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Journal of Genetic Syndromes & Gene Therapy

Journal of Genetic Syndromes & Gene Therapy
Open Access

ISSN: ISSN: 2157-7412

Abstract

Development of a New Third-Party Unit for Adult Stem Cell Transplantation using Clinical-Grade Rejected Cord Blood Units

Linda Peltier, Richard Brown, Yury Monczak, Gizelle Popradi, John Storring and Pierre Laneuville

Cord blood is a valuable alternative source of Hematopoietic Stem Cells (HSC) for the transplantation of
patients without a related stem cell donor. Even though the number of banked units has increased in recent years, units containing sufficient stem cells for transplantation into larger adult recipients are still very limited. Different approaches have been used to increase the number of infused HSC. However, most approaches have the disadvantage of increasing the cost of graft procurement or rely on a related haplo-identical donor who may not be available. We developed an alternative approach by creating a third-party unit of enriched CD34+ cells from a pool of multiple, human leukocyte antigen (HLA)-blind, cryopreserved CBUs. These pooled units were rejected by the public cord blood bank due to insufficient volumes and/or low nucleated cell counts. Seven recipients with hematological cancers received myeloablative conditioning followed by co-infusion of a ≥ 4/6 HLA-compatible CBU and a third-party source of CBUs consisting of CD34+ cells selected from a pool of cryopreserved CBUs. Six patients were engrafted with a median neutrophil engraftment time of 19.5 (15-29) days. All engrafted patients had 100%  HLA-matched CBU chimerism on day +14. All recipients had grades I-III acute graft-versus-host-disease (GVHD) that responded promptly to treatment, and no patients developed chronic GVHD. Two patients died, one on day +28
due to disease relapse, and one on day +360 due to multisystem organ failure. This new method not only supports the goal of increasing the number of HSCs to enable rapid engraftment, but it also demonstrates that clinical-grade rejected CBUs can be used to create a third-party, HLA-blind source of enriched CD34+ cells to support a small, ≥ 4/6 HLA-compatible CBU.

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