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Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Realization of that potential has been impeded by the need for myeloablative conditioning of the host and development of graft-versus-host disease (GVHD). To surmount these impediments, we have adapted a costimulation blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The protocol combines donor-specific transfusion (DST) with anti-CD154 mAb. When applied to stem cell transplantation, administration of DST, anti-CD154 mAb, and allogeneic bone marrow leads to hematopoietic chimerism and central tolerance with no myeloablation and no GVHD. Tolerance in this system results from deletion of both peripheral host alloreactive CD8+ T cells and nascent intrathymic alloreactive CD8+ T cells. In the absence of large numbers of host alloreactive CD8+ T cells, the transfusion that precedes transplantation need not be of donor origin, suggesting that both allospecific and non-allospecific mechanisms regulate engraftment. Agents that interfere with peripheral transplantation tolerance impair establishment of chimerism. We conclude that robust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of host myeloablative conditioning using a peripheral transplantation tolerance protocol.
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http://dx.doi.org/10.1172/JCI18599 | DOI Listing |
Lancet Rheumatol
December 2024
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Pharming Healthcare, Warren, NJ, USA. Electronic address:
Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.
Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT.
Stem Cell Res Ther
December 2024
Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107, West Yan Jiang Road, Guangzhou, 510120, Guangdong, China.
Background: Allo-HSCT is a curative therapy for patients with transfusion-dependent thalassemia (TDT). The high incidence of transplant-related complications is becoming an obstacle to safe and effective unrelated donor (URD) transplantation.
Methods: In this retrospective study, we reported the survival outcomes and complications of transplantation in thalassemia patients using a novel regimen consisting of pre-transplantation immunosuppression (PTIS) and modified myeloablative conditioning based on intravenous busulfan, cyclophosphamide, fludarabine, and rabbit anti-human thymocyte immunoglobulin.
Int J Hematol
December 2024
Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan.
Objective: Chimerism analysis is an important post-transplant assessment for allogeneic hematopoietic stem cell transplant (HCT) recipients. Although various chimerism analysis techniques are already established, they are limited in terms of sensitivity, versatility, and turnaround time. Our objective was to develop a digital droplet polymerase chain reaction (ddPCR) assay for chimerism analysis using ABO gene polymorphisms as markers.
View Article and Find Full Text PDFAnn Hematol
December 2024
Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Transient abnormal myelopoiesis (TAM) generally affects newborns with Down syndrome and is associated with constitutional trisomy 21 and a somatic GATA1 mutation. Here we describe a case of TAM which evolved after umbilical cord blood transplantation (UCBT), whose origin was identified as a GATA1 mutation-harboring clone in umbilical cord blood (UCB) by detailed genetic analyses. A 58-year-old male who received UCBT for peripheral T-cell lymphoma presented progressive anemia and thrombocytopenia, and leukocytosis with blast cells in the peripheral blood (PB).
View Article and Find Full Text PDFTransfus Med Hemother
December 2024
Blood Transfusion Institute of Serbia, Belgrade, Serbia.
Introduction: ABO blood type changes after ABO-incompatible hematopoietic stem cell transplantation (HSCT). Most non-hematopoietic tissues retain the expression of the patient's own ABO antigens, which may adsorb from the plasma onto the donor's red blood cells (RBCs). Because of this phenomenon, a persistent patient's A and/or B antigen could be detected in the laboratory, despite 100% white cell donor chimerism.
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