Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia.
The role of chimerism analysis as a prognostic indicator of relapse after hematopoietic stem cell transplantation (SCT) is controversial. We monitored chimerism status by short tandem repeat-based polymerase chain reaction (PCR) in T- and non-T-cell subsets and retrospectively evaluated clinical outcome in 96 patients with acute myeloid leukemia after myeloablative (MA) or reduced-intensity conditioning SCT. Fifty-six percent of 80 patients in the MA group demonstrated complete donor chimerism (CC) at all time points, whereas 6% had decreasing mixed chimerism (MC), 8% stable MC, 25% increasing MC and 3% increasing and decreasing MC. In 16 RIC patients, these percentages were 12, 50, 6, 6 and 19, respectively, together with 6% nonengraftment. Forty-three out of 96 patients experienced relapse. The last chimerism evaluation before relapse revealed increasing MC in only eight patients. In samples taken between 1 and 6 months post SCT, CC/decreasing MC was significantly related with a lower risk of relapse (31 versus 83%, P<0.000) and mortality (38 versus 83%, P<0.000) than with MC/increasing MC. However, the development of relapse was very rapid. Only very frequent monitoring of chimerism status by highly sensitive methods might identify impending relapse and allow early immunological intervention.
Huisman
C
C
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. c.huisman@umcutrecht.nl
de Weger
R A
RA
de Vries
L
L
Tilanus
M G J
MG
Verdonck
L F
LF
D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D046528:Chimerism; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012008:Recurrence; D018183:Transplantation Chimera / Q000235:genetics*; D014184:Transplantation, Homologous