Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias.
OBJECTIVE
In patients with acute myeloblastic leukemia with t(8;21) or inv(16) aberrations (core binding factor [CBF] leukemias), minimal residual disease (MRD) can be sensitively detected during and after chemotherapy by use of molecular methods. However, the prognostic impact of qualitative MRD detection is still under debate. In this study, the prognostic value of MRD quantification in patients with CBF leukemias was assessed.


METHODS
We quantified MRD at various time points during and after therapy by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for AML1/MTG8 and CBFB/MYH11 in 37 patients with CBF leukemias treated within a multicenter trial.


RESULTS
At initial diagnosis, the patients showed a heterogenous fusion gene expression relative to glyceraldehyde 3-phosphate dehydrogenase with a variation of more than two log steps. According to MRD status during/after therapy, two groups of patients were separated. Of the 26 patients who had MRD levels of less than 1% in relation to initial diagnosis at all time points tested after induction chemotherapy, only two experienced relapse after a median follow-up of 19 months. Of the 11 patients who had a sample with an MRD level >/= 1% at least at one time point after induction therapy, 10 experienced relapse, with a median remission duration of 10 months (P <.001). The median interval between the informative MRD sample and clinical relapse in these patients was 3 months.


CONCLUSIONS
MRD quantification by real-time RT-PCR allows the identification of patients with a high risk of relapse among the CBF leukemias.
Krauter
Jürgen
J
Department of Hematology/Oncology, Hannover Medical School, Carl-Neuberg-Str 1, D-30625 Hannover, Germany. krauter.juergen@mh-hannover.de
Gorlich
Kerstin
K
Ottmann
Oliver
O
Lubbert
Michael
M
Dohner
Hartmut
H
Heit
Wolfgang
W
Kanz
Lothar
L
Ganser
Arnold
A
Heil
Gerhard
G
D000293:Adolescent; D000328:Adult; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D000075142:RUNX1 Translocation Partner 1 Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)