Chimerism testing in allogeneic hematopoietic stem cell transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established treatment option for a variety of malignant and nonmalignant diseases. Each year, more than 28,000 patients undergo allogeneic HSCT worldwide. Molecular analysis of chimerism levels is used to monitor the proportions of donor and recipient hematopoietic cells in patients after HSCT. Chimerism studies can help identify the source of hematopoiesis after engraftment, identify graft rejection in patients with poor hematologic recovery, and assist in the diagnosis and prediction of relapse and clinical graft-vs-host disease (GVHD). The most commonly applied method is PCR amplification of short tandem repeats (STR), a type of genetic polymorphism. The interpretation of chimerism results depends on the context in which the testing was done, i.e., the type of transplant, conditioning intensity, timing of testing post-transplant and results of concurrent blood counts and bone marrow morphology. While the methodology is technically straightforward, the implementation, analysis, and interpretation of results can be complicated. The clinical importance of chimerism results warrants the effort required by the laboratory for validation and performance of the test. In this chapter we review the clinical utility of chimerism analysis and laboratory aspects of testing, including methods, reagents, approaches to pr-and post-transplant testing, analysis and interpretation, pitfalls and limitations, reporting, and data management.