whom HCT-CI appeared to be crucially important was the group of patients at high risk for disease relapse (beyond CR1/CR2 or with high-risk cytogenetics). A high HCT-CI in these patients resulted in uniformly negative outcomes. This group of patients with very poor prognosis should probably not be transplanted. Lastly, the intermediaterisk group could be the group that would benefit the most from posttransplant interventions to decrease relapse rate. This analysis is limited by a relatively small number of patients treated with haploidentical transplants only. Factors included in the risk model were selected from significant factors identified in the multivariable model for PFS without weighting of the prognostic impact of each component. This model needs to be validated in a larger number of patients, including HLA-matched transplants, as it could have major implications in treatment decisions.In conclusion, risk stratification models combining disease and patient characteristics could further refine prognosis for potential ASCT patients, better identify patients who could benefit from maintenance therapies posttransplant, as well as serve as a tool to further compare results among different studies.
Although RBC transfusion can result in the development of anti-RBC alloantibodies that increase the probability of life-threatening hemolytic transfusion reactions, not all patients generate anti-RBC alloantibodies. However, the factors that regulate immune responsiveness to RBC transfusion remain incompletely understood. One variable that may influence alloantibody formation is RBC alloantigen density. RBC alloantigens exist at different densities on the RBC surface and likewise exhibit distinct propensities to induce RBC alloantibody formation. However, although distinct alloantigens reside on the RBC surface at different levels, most alloantigens also represent completely different structures, making it difficult to separate the potential impact of differences in Ag density from other alloantigen features that may also influence RBC alloimmunization. To address this, we generated RBCs that stably express the same Ag at different levels. Although exposure to RBCs with higher Ag levels induces a robust Ab response, RBCs bearing low Ag levels fail to induce RBC alloantibodies. However, exposure to low Ag–density RBCs is not without consequence, because recipients subsequently develop Ag-specific tolerance. Low Ag–density RBC–induced tolerance protects higher Ag–density RBCs from immune-mediated clearance, is Ag specific, and occurs through the induction of B cell unresponsiveness. These results demonstrate that Ag density can potently impact immune outcomes following RBC transfusion and suggest that RBCs with altered Ag levels may provide a unique tool to induce Ag-specific tolerance.
Alloantibodies developing after exposure to red blood cell (RBC) alloantigens can complicate pregnancy and transfusion therapy. The only method currently available to actively inhibit RBC alloantibody formation is administration of antigen-specific antibodies, a phenomenon termed antibody-mediated immune suppression (AMIS). A well-known example of AMIS is RhD immune globulin prophylaxis to prevent anti-D formation in RhD− individuals. However, whether AMIS is specific or impacts alloimmunization to other antigens on the same RBC remains unclear. To evaluate the specificity of AMIS, we passively immunized antigen-negative recipients with anti-KEL or anti-hen egg lysozyme (HEL) antibodies, followed by transfusion of murine RBC expressing both the HEL-ovalbumin-Duffy (HOD) and human KEL antigens (HOD × KEL RBC). Significant immunoglobulin G deposition on transfused HOD × KEL RBC occurred in all passively immunized recipients. Complement deposition and antigen modulation of the KEL antigen occurred on transfused RBC only in anti-KEL–treated recipients, whereas HEL antigen levels decreased only in the presence of anti-HEL antibodies. Western blot analysis confirmed the specificity of antigen loss, which was not attributable to RBC endocytosis and appears distinct for the 2 antigens. Specifically, removal of KEL was attenuated by clodronate treatment, whereas loss of HEL was unaffected by clodronate in vivo but sensitive to protease treatment in vitro. Antigen-specific modulation correlated with antigen-specific AMIS, with anti-KEL treated recipients forming antibodies to the HOD antigen and anti-HEL–treated recipients developing antibodies to the KEL antigen. Together, these results demonstrate that passively administered antibodies can selectively inhibit the immune response to a specific antigen.
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