Myeloid Leukemia

Chimerism Analysis 275
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Chimerism Analysis Following Nonmyeloablative
Stem Cell Transplantation
Thomas Lion and Franz Watzinger
Summary
Molecular monitoring of hematopoietic chimerism has become a routine diagnostic approach
in patients after allogeneic stem cell transplantation. Chimerism testing permits the documentation
and surveillance of engraftment and facilitates early detection of impending graft rejection.
In patients transplanted for treatment of malignant hematological disorders, monitoring of
chimerism can provide an early indication of incipient disease relapse. The investigation of
chimerism has therefore become an indispensable tool for the management of patients during
the posttransplant period. Growing use of nonmyeloablative conditioning, which is associated
with prolonged duration of mixed hematopoietic chimerism, has further increased the clinical
importance of chimerism analysis. At present, the most commonly used technical approaches
to the investigation of chimerism include microsatellite analysis by polymerase chain reaction
and, in the gender-mismatched transplant setting, fluorescence in situ hybridization analysis of
sex chromosomes. The investigation of chimerism within specific leukocyte subsets isolated
from peripheral blood or bone marrow samples by flow-sorting or magnetic bead-based techniques
provides more specific information on processes underlying the dynamics of donor/
recipient chimerism. Moreover, cell subset-specific analysis permits the assessment of impending
complications at a significantly higher sensitivity, thus providing a basis for earlier treatment
decisions.
Key Words: Chimerism; microsatellites; FISH; leukocyte subsets; flow-sorting; graft
rejection; relapse.
1. Introduction
Investigation of donor- and recipient-derived hematopoiesis (chimerism) by
molecular techniques facilitates the monitoring of engraftment kinetics in
patients after allogeneic stem cell transplantation. The analysis of chimerism
during the immediate posttransplant period permits early assessment of successful
engraftment or graft failure (1,2). Patients receiving reduced intensity
(nonmyeloablative) conditioning regimens have an increased risk of graft
From: Methods in Molecular Medicine, Vol. 125: Myeloid Leukemia: Methods and Protocols
Edited by: H. Iland, M. Hertzberg, and P. Marlton © Humana Press Inc., Totowa, NJ
275