Diagnostic chimerism analysis after allogeneic stem cell transplantation: new methods and markers.
Analysis of chimerism after allogeneic hematopoietic cell transplantation is important for assessing engraftment and the early detection of graft failure. In addition, the monitoring of minimal residual disease and early detection of imminent relapse has also become an important issue. Novel transplant procedures, for example dose-reduced conditioning protocols, rely on chimerism analysis to guide intervention, i.e. the reduction of immunosuppression or infusion of donor lymphocytes. During the last 30 years, several methods for the analysis of chimerism after hematopoietic cell transplantation have been published. Currently, fluorescent in situ hybridization (XY-FISH) analysis of sex chromosomes after transplantation from a sex-mismatched donor or analysis of polymorphic DNA sequences, i.e. short tandem repeats (STR) or variable number of tandem repeats (VNTR), are the most widely used procedures used in the assessment of chimerism. Two major diagnostic fields can be defined for chimerism analysis: the period of engraftment and the detection of minimal residual disease. Although STR-PCR and FISH analysis are very useful in the diagnosis of engraftment and graft failure, they are only of limited use in the monitoring of minimal residual disease, largely because of its limited level of sensitivity (1-5% for the minor population). Several novel procedures to improve this level of detection have been reported in recent years. One focus has been the use of real-time PCR techniques based on analysis of the Y-chromosome or, more recently, single nucleotide polymorphism (SNPs). These procedures combine quantitative analysis with high sensitivity (10(-4) to 10(-6)), and hold great potential for the future. In addition, the combination of cell sorting based on leukemia-specific immunophenotype and STR-PCR has been successfully used for minimal residual disease detection. First clinical data using these procedures indicate that intervention (e.g. the reduction of immunosuppression or donor lymphocyte infusion) may be effective in the minimal residual disease situation, even in high risk diseases like acute myeloid leukemia and acute lymphoblastic leukemia. The optimal timing of these diagnostic interventions is a critical issue and has to be further optimized. Whether this will ultimately improve the survival of patients with leukemia after transplantation has to be shown in prospective studies.
Thiede
Christian
C
Medical Department, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
D000818:Animals; D005819:Genetic Markers; D006801:Humans; D017403:In Situ Hybridization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D018183:Transplantation Chimera / Q000235:genetics*; D017211:Treatment Failure
D005819:Genetic Markers