Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse.
BACKGROUND
The reoccurrence or increase in autologous hematopoiesis after allogeneic transplantation has been linked to incipient leukemia relapse. However, the importance of such an emergency regarding microchimerism (i.e. mixed chimerism below 1% of autologous cells) still remains controversial, as fluctuating microchimerism can be observed for a very long time after transplantation.


METHODS
Using real-time PCR (RQ-PCR), we compare peripheral blood samples obtained from patients with acute myeloid leukemia (AML) before hematological relapse and those taken during complete remission (i.e. either complete cytogenetic remission or complete molecular remission where applicable). By comparison of these two groups, we describe microchimerism dynamics clearly connected with imminent AML relapse. Additionally, we compare applicability of RQ-PCR and conventional PCR with fragment analysis.


RESULTS
Mere reappearance of autologous hematopoiesis within patients with complete donor chimerism is alarming, and another sample with further increase confirms ongoing relapse. In case of patients with continuous microchimerism, another two consecutive samples with increasing trend are required. RQ-PCR predicted a significantly higher number of hematological relapses (87%vs. 39%) with a median anticipation period of 33 days, 26 days earlier than conventional PCR (P= 0.0002). Moreover, the outcome of microchimerism dynamics was in complete agreement with monitoring of minimal residual disease when analyzed from the same cell compartment.


CONCLUSIONS
Within this paper, we emphasize the importance of microchimerism monitoring as a reliable indicator of incipient AML relapse, especially in patients where no other specific molecular marker is available.
Horky
O
O
Center of Molecular Biology and Gene Therapy, Department of Internal Medicine-Hematooncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Cernopolni 9, Brno, Czech Republic. ohorky@fnbrno.cz
Mayer
J
J
Kablaskova
L
L
Razga
F
F
Krejci
M
M
Kissova
J
J
Borsky
M
M
Jeziskova
I
I
Dvorakova
D
D
D000328:Adult; D005819:Genetic Markers; D005820:Genetic Testing; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D014178:Translocation, Genetic / Q000235:genetics; D018183:Transplantation Chimera / Q000235:genetics*; D055815:Young Adult
D005819:Genetic Markers