Molecular disease eradication is a prerequisite for long-term remission in patients with t(8;21) positive acute myeloid leukemia: a single center study.
Association of long-term clinical remission and molecular disease-eradication is well established in acute myeloid leukemia (AML) patients with t(15;17) and inv(16). In patients with t(8;21) positive AML no consensus exists over the disappearance of the AML1/ETO fusion transcript during the course of disease and most studies reported reverse transcriptase polymerase chain reaction (RT-PCR) positivity as a common finding after consolidation chemotherapy, autologous and allogeneic stem cell transplantation (alloSCT). In our single center study, we performed RT-PCR monitoring in 14 patients with t(8;21) in CR1 (n = 13) and/or CR2 (n = 4). The median number of bone marrow (BM) and/or peripheral blood (PB) samples per patient was 18 (range, 2-43). In 5 out of 6 cases relapse occurred after persistence of minimal residual disease (MRD) in CR for 4-14 months. The sixth patient relapsed despite molecular remission (MR) in BM and PB for 3 months, molecular relapse preceded hematological relapse for 7 months. Eleven patients with a median follow-up of 7.8 (range, 1.5-15.4) years are in persistent CR and MR after consolidation chemotherapy (n = 7). mainly with repetitive cycles of high-dose Ara-C, autologous (n = 1) or myeloablative allogeneic (n = 3) stem cell transplantation. Molecular remission was attained immediately after alloSCT, but after 6-26 months in CR in patients with consolidation chemotherapy. In 7 patients, MRD was only studied in long-term remission. In conclusion, long-term CR was associated with persistent molecular disease-eradication. In our patients, molecular remission was a prerequisite but not a guarantee for long-term disease-free survival. Hematological relapse never occurred without prior molecular relapse. Due to the slow kinetics of AML1/ETO after consolidation chemotherapy the value of qualitative RT-PCR to predict early relapse is limited. In this situation quantitative RT-PCR might help to define individual relapse risk and to improve as well as facilitate clinical decision-making.
Department of Medicine I, Bone Marrow Transplantation Unit, University Hospital of Vienna, Vienna, Austria. Margit.Mitterbauer@akh-wien.ac.at
Margit
M
Mitterbauer
Gerlinde
G
Mitterbauer-Hohendanner
Wolfgang R
WR
Sperr
Peter
P
Kalhs
Hildegard T
HT
Greinix
Christa
C
Fonatsch
Oskar A
OA
Haas
Ulrich
U
Jäger
Christine
C
Mannhalter
Klaus
K
Lechner
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000401:mortality; D011237:Predictive Value of Tests; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D016896:Treatment Outcome