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...

WE recently reported that the acceptance of wholeorgan transplants connotes (and requires) a special kind of mixed chimerism involving an exchange between organ and recipient oflymphodendritic leukocytes (Fig 1 ).1 The consequence in five of five patients studied 27 to 29V2 years after kidney transplantation from HLA-mismatched donors was the diffuse presence of donor dendritic cells in the lym...

BACKGROUND Use of a reduced-intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a coexistence of both host and donor hematopoietic cells may influence posttransplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) ...

We analyzed the kinetics of CD3 chimerism in 120 consecutive allogeneic hematopoietic cell transplantation (HCT) recipients receiving alemtuzumab-based conditioning. Fifty-two received fludarabine/melphalan, 44 received fludarabine/busulfan, and 24 received clofarabine/melphalan in addition to alemtuzumab. Post-transplant GVHD prophylaxis consisted of tacrolimus. No prophylactic donor lymphocyt...

BACKGROUND Langerhans cells (LCs) are self-renewing epidermal myeloid cells that can migrate and mature into dendritic cells. Recipient LCs that survive cytotoxic therapy given in preparation for allogeneic hematopoietic cell transplantation may prime donor T cells to mediate cutaneous graft-versus-host disease (GVHD). This possible association, however, has not been investigated in the setting...

Peripheral destruction of sickled erythrocytes is a cardinal feature of sickle cell disease (SCD). Less well established is the potential contribution of ineffective erythropoiesis to the pathophysiology of this hemoglobinopathy. Since patients with SCD frequently develop mixed hematopoietic chimerism after allogeneic nonmyeloablative stem cell transplantation, we used this opportunity to direc...

Although the inhibitory receptor CTLA-4 (CD152) has been implicated in peripheral CD4 T-cell tolerance, its mechanism of action remains poorly defined. We analyzed mechanisms of CD4 cell tolerance in a model of tolerance induction involving establishment of mixed hematopoietic chimerism in recipients of fully MHC-mismatched allogeneic bone marrow cells with anti-CD154 mAb. Animals lacking CD80 ...

BACKGROUND Tolerance to cardiac allografts has not been achieved in large animals using methods that are readily applicable to human recipients. We investigated the effects of mixed hematopoietic chimerism on cardiac allograft survival and chronic rejection in miniature swine METHODS Recipients were T-cell depleted using a porcine CD3 immunotoxin, and each received either of two nonmyeloablat...

OBJECTIVE To determine the sensitivity and significance of B-cell chimerism for the detection of early engraftment, transplant rejection, and disease relapse. METHODS The dynamic monitoring of lineage-specific cell subtypes (B, T, and NK cells) was made in 20 B-cell acute lymphoblastic leukemia (B-ALL) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the e...

We combined the polymerase chain reaction (PCR) with oligonucleotide hybridization as a novel and sensitive technique to evaluate posttransplant chimerism. Specific oligonucleotides for hybridization were synthesized homologous to tandemly repetitive core sequences of regions with a variable number of tandem repeats (VNTRs). Polymorphisms at such loci result from allelic differences in the numb...