الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Following up patients after HSCT by chimerism detection can detect the outcome; engraftment, relapse or rejection. Many variables affect the result of chimerism either increasing or decreasing mixed chimerism. Detection of chimerism by Lineage specific method is specific and sensitive than chimerism detection by whole blood. In this study, the importance of these variables on the outcome of chimerism detection are highlighted.
States of mixed chimerism can have varied significance depending on the underlying disease for which the transplant was performed, the conditioning regimen, the level of mixed chimerism, the trend in degree of mixed chimerism and the lineage of the cells assessed in the chimerism assay.
Many studies had detected the predictive value of mixed chimerism (MC) in an individual patient for either graft rejection or relapse. Some studies indicate that MC is associated with these complications, while others disagree with this finding.
Thus, there appear to be states where mixed chimerism results in a peaceful state, where stable levels of MC may indicate a tolerant state associated with no GVHD and no graft rejection with possible continued presence of a graft versus tumor effect. In other cases, however, a state of increasing mixed chimerism can be associated with host versus graft effects and risk for rejection and, possibly, for increased risk of disease relapse. Improved sensitivity of chimerism assays, increased use of lineage-specific chimerism and a better sense of the appropriate timing of the use of chimerism testing post transplantation may allow resolution of some of the controversy regarding the significance of a mixed chimeric state.
On the other hand, decreasing MC, often seen after tapering of immunosuppression after transplant or after donor lymphocytes infusion (DLI), may be an early predictor of graft-versus-host disease (GVHD) and of its more desirable counterpart graft versus- tumor effect.
Eventually, determining chimerism may also be useful to monitor response to a DLI or help to decide administering prophylactic DLI in specific situations (e.g., to potentiate graft-versus-tumor effect or to prevent incipient graft rejection in some cases of increasing MC).
The main goal of this study is to analyze chimerism state by using lineage specific chimerism and compare it with whole blood chimerism and also using a semi-quantification method in case of mixed chimerism in order to provide complementary information to predict the outcome of HSCT and allow rapid interference in case of relapse or rejection.
The present work presents preliminary results of lineage-specific donor chimerism assessment in a selected group of patients. The most important question is whether lineage specific chimerism analysis is superior to whole blood chimerism for follow up after HSCT. The expected obstacle is the cost effectiveness of this method. The question arises whether there is a specific subgroup of patients that would benefit the most.
The absence of finding a difference in results between lineage specific and whole blood chimerism analysis in this study, may be as a result of limited study group, the high variety of diseases included in the study or the limited sorted cells namely: T-lymphocytes (CD3+) and neutrophils (CD33+).Consequently, there is a need for further studies on a larger group of patients with uniform diagnosis for serial chimerism assessment withmore different cell lines for a long-term follow up period.
Also, the results of this study indicate that chimerism detection by VNTR is dependaple method to follow up patients after HSCT. However, some cases need some modifications as repeated analysis, short duration between each analysis, lineage specific in comparison to whole blood analysis and dilution experiments in order to predict the outcome.
At this point in time, available technologies to determine chimerism do not always allow for distinguishing between the absence of engraftment or delayed engraftment or between disease relapse and delayed graft rejection. Timely use of lineage-specific chimerism assays with sensitive means to detect minimal residual disease will therefore offer important insights to improve therapeutic benefit of HSCT in the future.
In addition to understanding the significance of early T-cell chimerism and standardizing sampling frequency and methodologies by which this is established, increased knowledge of which T-cell subsets are important for tolerance induction and maintenance of graft versus tumor effects without exacerbation of GVHD will be necessary to develop improved strategies to generate grafts that have adequate proportions of these T cells with the capability of homing and expansion, with the ultimate goal of achieving lasting stable mixed chimerism. For example, selective expansion of regulatory T-cells might allow establishment of a state of tolerance with preservation of any needed graft versus tumor effect.