Relevance of presenting white blood cell count and kinetics of molecular remission in the prognosis of acute myeloid leukemia with CBFbeta/MYH11 rearrangement.
OBJECTIVE
The detection of CBFbeta/MYH11 transcripts by RT-PCR has became a valuable and widely used technique in the accurate cytogenetic and molecular classification of acute myeloid leukemia (AML), but the clinical value of RT-PCR for monitoring minimal residual disease (MRD) during follow-up remains unclear.


METHODS
We analyzed the factors predicting relapse and the value of MRD monitoring by RT-PCR in a series of 16 patients with CBFb/MYH11-positive AML (15 M4Eo; 1 M4). Fifteen were newly diagnosed cases (CR1) and one was studied after first relapse (CR2). Eight patients had clinical relapse at 6 to 19 months from the achievement of CR.


RESULTS
Presenting WBC count had a significant prognostic influence on disease-free survival (p=0.001). All four patients with a WBC count >100x10(9)/L relapsed, while only four additional relapses occurred among the eleven patients who had an initial WBC count below 100x10(9)/L. With regards to molecular monitoring, all relapses but one occurred in patients who showed persistent RT-PCR positivity during hematologic remission. By contrast, conversion to a repeatedly PCR-negative status was observed in the seven patients who remained in CR1 after a median follow-up of 48 months (range 31-79 months), as well as in the transplanted patient who was monitored in CR2. In these patients a PCR-positivity could be detected up to 24 months after diagnosis (median time to conversion to PCR-negative: 8 months).


CONCLUSIONS
In conclusion, marked hyperleukocytosis (>100x10(9)/L) confers poor prognosis to the patient with CBFbeta/MYH11-positive AML. In addition, slow kinetics of molecular remission was observed in this subset of AML, but the CBFb/MYH11 fusion transcript is no longer detectable in long-term survivors, indicating that molecular remission is an important therapeutic goal.
Martín
G
G
Servicio de Hematología, Hospital Universitario La Fe, Av. Campanar 21, 46009 Valencia, Spain.
Barragán
E
E
Bolufer
P
P
Chillón
C
C
García-Sanz
R
R
Gómez
T
T
Brunet
S
S
González
M
M
Sanz
M A
MA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002869:Chromosome Aberrations / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D025063:Chromosome Disorders; D002885:Chromosomes, Human, Pair 16; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis; D015514:Oncogene Proteins, Fusion / Q000097:blood / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger