Effects of Mobilization Regimens in Donors on Outcomes of Hematopoietic Cell Transplantation in Miniature Swine
Abstract:Toxicities and complications associated with hematopoietic cell transplantation currently limit this potentially curative therapy for malignant and nonmalignant blood disorders. Miniature swine provide a clinically relevant model for studies to improve posttransplantation outcomes. Miniature swine recipients of high-dose haploidentical hepatopoietic cell transplantation after reduced-intensity conditioning consisting of low-dose (100 cGy) total-body irradiation, partial T-cell depletion by using a CD3 immunotoxin, and a 45-d course of cyclosporine A typically successfully engraft without graft-versus-host disease. We recently observed broad variability in engraftment outcomes that correlates with the occurrence of adverse reactions in donors after cytokine treatment to mobilize hematopoietic progenitor cells from the bone marrow to the peripheral blood for collection. Haploidentical recipients (n = 16) of cells from donors remaining healthy during cytokine treatment engrafted with multilineage chimerism, did not develop graft-versus-host disease, and did not require any blood products. In comparison, identically conditioned recipients of cells from donors that had severe reactions during cytokine treatment had adverse outcomes, including the development of clinically significant thrombocytopenia requiring blood product support in 8 of 11 swine. Furthermore, all 11 recipients lost peripheral blood myeloid chimerism (indicating lack of engraftment of donor stem cells). These data suggest that posttransplantation complications in swine are influenced by the health status of the donor before and during the collection of hematopoietic cells by leukapheresis.
Document Type: Research Article
Affiliations: 1: Transplantation Biology Research Center, and Transplant Center, Massachusetts General Hospital, Boston, Massachusetts, USA 2: Cancer Center, and Transplant Center, Massachusetts General Hospital, Boston, Massachusetts, USA 3: Infectious Disease Division, and Transplant Center, Massachusetts General Hospital, Boston, Massachusetts, USA 4: Transplantation Biology Research Center, and Transplant Center, Massachusetts General Hospital, Boston, Massachusetts, USA; Columbia Center of Translational Immunology, Columbia University, New York, New York, USA. Rd2605@columbia.edu
Publication date: December 1, 2012
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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