Chimerism studies with quantitative real-time PCR in stem cell recipients with acute myeloid leukemia.
OBJECTIVE
Chimerism is well-established for surveillance of acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (HSCT), but interpretation of the results and techniques is not standardized.


METHODS
We correlated chimerism in 75 AML patients (38 male, 37 female) who underwent myeloablative (n = 36)/reduced (n = 39) allo-HSCT with the risk of relapse and survival. Chimerism was evaluated by quantitative real-time polymerase chain reaction for donor/recipient specific polymorphisms/Y-specific sequences.


RESULTS
After HSCT, 40 patients (53%) achieved stable complete donor chimerism (≥ 99.0% of donor alleles), while 35 (47%) failed to achieve stable donor chimerism. Thirty-one patients (41%) showed decreasing donor alleles after having first achieved complete donor chimerism. To investigate the kinetics of mixed chimerism, patients were separated whether they showed subsequent increasing or decreasing donor alleles. Subsequent decrease of donor alleles was associated with relapses in 17 of 18 cases (94%), while no patient with subsequent increasing donor alleles relapsed (p < 0.001). Patients with mixed chimerism and increasing donor alleles had better 2-year disease-free survival (85%) than those with decreasing donor alleles (0%; p < 0.001).


CONCLUSIONS
The kinetics of mixed chimerism as assessed by quantitative real-time polymerase chain reaction is an important prognostic predictor in the post-transplantation period of AML patients.
Wiedemann
Bettina
B
Interdisciplinary Clinic for Stem Cell Transplantation, University of Hamburg, Martinistrasse 52, Hamburg, Germany.
Klyuchnikov
Evgeny
E
Kröger
Nicolaus
N
Zabelina
Tatjana
T
Stahl
Tanja
T
Zeschke
Silke
S
Badbaran
Anita
A
Ayuk
Francis
F
Alchalby
Haefaa
H
Wolschke
Christine
C
Bokemeyer
Carsten
C
Fehse
Boris
B
Zander
Axel Rolf
AR
Bacher
Ulrike
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction / Q000379:methods*; D012008:Recurrence; D012189:Retrospective Studies; D018183:Transplantation Chimera
D009687:Nuclear Proteins; D000090243:Nucleophosmin