We investigated the chimerism pattern within flow-sorted peripheral blood- or bone marrow-derived cell populations after allogeneic bone marrow transplantation (BMT) for the treatment of leukemia in children. This study was performed to define the identity of persistent host-type cells, to identify prognostic variables for the persistence of host-type hematopoiesis, and to determine the prognostic significance of the chimerism pattern on the duration of the leukemia-free interval, the overall survival, and the leukemia-free survival. The patients received either HLA-identical non-T-cell-depleted (n = 46) or HLA nonidentical T-cell-depleted (n = 7) BMT. In the peripheral blood, the children showed either stable mixed chimerism (SMC; ie, persistent host-type hematopoiesis; n = 14), (transient) mixed T-lymphoid chimerism (MTLC; n = 9), or complete chimerism (CC; n = 30). In the bone marrow, only donor-type cells were found in children with either CC (n = 8) or MTLC (n = 2), and a mixture of donor- and recipient-type cells was found in children with SMC (n = 7). The persistence of host-type hematopoiesis (SMC) was significantly related to a lower age of the recipient, the type of conditioning regimen, a lower total body irradiation dose, T-cell depletion of the bone marrow graft, and the use of cyclosporine A for acute graft-versus-host disease prophylaxis. No significant differences were found between patients with (SMC) or without (CC/MTLC) persistent host-type hematopoiesis with respect to the duration of the leukemia-free interval, the overall survival, or the leukemia-free survival. We conclude that ablation of host-type hematopoiesis is not compulsory for long-term leukemia-free survival after allogeneic BMT for various hematologic malignancies.
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PLoS One
May 2016
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT.
View Article and Find Full Text PDFTransfusion
February 2015
Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Background: Immune hemolytic anemia is a well-known complication after allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant hemolytic anemia results in increased red blood cell transfusions and medical sequelae including iron overload.
Case Report: We present a case report of immune hemolytic anemia that occurred after allogeneic HSCT from an ABO major-mismatched, HLA-matched unrelated donor.
Diabetes
June 2014
Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CADepartment of Diabetes Research, Beckman Research Institute, City of Hope, Duarte, CADepartment of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope, Duarte, CA
Destruction of pancreatic islet β-cells in type 1 diabetes (T1D) is mainly mediated by autoimmune T and B lymphocytes. We reported that induction of major histocompatibility complex (MHC)-mismatched mixed chimerism reversed autoimmunity and reestablished thymic negative selection of autoreactive T cells in NOD mice, but it is still unclear how mixed chimerism tolerizes autoreactive B cells. The current studies were designed to reveal the mechanisms on how mixed chimerism tolerizes autoreactive B cells in T1D.
View Article and Find Full Text PDFTransplantation
January 2010
Research School of Biology, The Australian National University, Canberra, Australia.
Background: Spleen as a lymphoid tissue is specialized for monitoring blood and mounting immunity against blood-borne antigens. Antigen-presenting cells present in spleen commonly develop from bone marrow-derived precursors that enter blood circulation. However, a distinct splenic myeloid antigen-presenting cell subset described in this laboratory, namely "dendritic-like cells" (L-DC), has been hypothesized not to share a bone marrow origin.
View Article and Find Full Text PDFJ Cell Mol Med
August 2010
Research School of Biology, The Australian National University, Canberra, Australia.
Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC.
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