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1872 Antithymocyte Globulin Treatment at the Time of Transplantation Impairs Donor Hematopoietic Stem Cell Engraftment

Experimental Transplantation: Basic Biology, Engraftment and Disease Activity
Program: Oral and Poster Abstracts
Session: 701. Experimental Transplantation: Basic Biology, Engraftment and Disease Activity: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Zheng Hu, PhD1*, Feng Jin1*, Jin He2*, Chunhui Jin3*, Wei Fan1*, Yanhong Shan1*, Zefeng Zhang1*, Liguang Sun1* and Yong-Guang Yang, MD, PhD4

1The First Hospital and Institute of Immunology, Jilin University, Changchun, China
2The First Hospital, Jilin University, Changchun, China
3Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons,, New York
4Center for Translational Immunology, Columbia University, New York

Antithymocyte globulin (ATG) is often included in the conditioning regimen to prevent graft-vs.-host disease in allogeneic hematopoietic stem cell (HSC) transplantation. However, because ATG contains antibodies targeting a wide range of antigens on human cells, its potential off-target effects remain a concern. Here, we explored this question in humanized mice that were made by transplantation of human fetal thymic grafts (under the renal capsule) and CD34+ human fetal liver cells (i.v.). We showed that ATG binds to almost all lineages of human hematopoietic cells including HSCs, and accordingly, it is capable of depleting almost all human hematopoietic cells. Interestingly, the efficacy of ATG was highly variable depending on the tissue of residence, with human cells in bone marrow significantly less susceptible than those in the blood and spleen. Recovery of multilineage human lymphohematopoietic reconstitution in humanized mice that received ATG 3 weeks after HSC transplantation indicates that ATG had a minimal effect on human HSCs that have settled in bone marrow niches. However, efficient human HSC depletion and engraftment failure were seen in mice receiving ATG immediately following transplantation. Our data indicate that the efficacy of ATG is tissue-dependent, and suggest a risk of impairing donor hematopoietic engraftment when ATG is used in preparative conditioning regimens in HSC transplantation.

Disclosures: No relevant conflicts of interest to declare.

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