Chimerism analysis by lineage-specific fluorescent polymerase chain reaction in secondary graft failure after allogeneic stem cell transplantation.
BACKGROUND
Chimerism analysis is essential in understanding the etiology of graft failure occurring after allogeneic stem cell transplantation. The detection of marrow and/or blood host cells suggests graft rejection, relapse of the underlying disease, or a state of stable mixed chimerism. However, complete donor chimerism may be observed in some cases. Our objective was to characterize, by a sensitive process of chimerism analysis, six cases of graft failure occurring after transplant.


METHODS
Six cases of secondary graft failure, in which previous analysis had shown complete donor chimerism by standard polymerase chain reaction amplification of variable number of tandem repeats, were studied. In order to detect a minority population of recipient cells, we increased the sensitivity of the process by using fluorescent polymerase chain reaction and analyzing the origin of T, B, and natural killer lymphocytes at the time of graft failure.


RESULTS
The complete donor origin of mononuclear cells and lymphocytic populations was confirmed with this method in five of six patients. In the remaining patient, diagnosis of graft failure was clarified by the detection of a previously undetected mixed chimerism, compatible with graft rejection. In the other five patients, graft rejection was thereby excluded and graft failure could be related to viral infection or to graft-versus-host disease.


CONCLUSIONS
Our sensitive process of fluorescent lineage-specific chimerism analysis may help in distinguishing between graft rejection and other mechanisms of graft failure, which is essential for deciding appropriate therapy.
Department of Hematology, Henri Mondor Hospital, Créteil, France.
S
S
Maury
H
H
Jouault
M
M
Kuentz
J P
JP
Vernant
M
M
Tulliez
C
C
Cordonnier
D
D
Bories
D000293:Adolescent; D000328:Adult; D019070:Cell Lineage / Q000528:radiation effects*; D005260:Female; D005453:Fluorescence; D006084:Graft Rejection / Q000209:etiology / Q000628:therapy; D006085:Graft Survival / Q000528:radiation effects*; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D018183:Transplantation Chimera