The prognostic value of MLL-AF9 detection in patients with t(9;11)(p22;q23)-positive acute myeloid leukemia.
OBJECTIVE
Translocation (9;11) is the most common t(11q23) in acute myeloid leukemia (AML). A considerable number of patients with this cytogenetic abnormality relapse and die of their disease. We evaluated the clinical significance of minimal residual disease (MRD) monitoring in t(9;11)(p22;q23)-positive AML patients using real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) analysis.


METHODS
We identified 34 newly diagnosed patients with t(9;11)(p22;q23)-positive AML treated within three multicenter trials of the AML Study Group. MRD could be investigated by RQ-PCR in 19 patients during and after therapy. Because of the relatively low sensitivity of the RQ-PCR (10(-3) to 10(-4) at the cellular level), samples from RQ-PCR-negative patients were also analyzed by nested polymerase chain reaction (nPCR; sensitivity 10-4 to 10-5 at the cellular level).


RESULTS
RQ-PCR monitoring revealed two groups of patients: group 1 (n=11) had negative RQ-PCR in all samples collected in hematologic complete remission whereas group 2 (n=8) had at least one positive RQ-PCR in samples collected in complete remission during therapy. Group 1 had a significantly lower cumulative incidence of relapse (p=0.004) and better overall survival (p=0.003) compared to group 2. nPCR did not add information to that gained from RQ-PCR. Molecular relapse was detected in two patients by RQ-PCR four and six weeks, respectively before hematologic relapse occurred. Quantitative MLL-AF9 levels at diagnosis or during and after therapy had no prognostic impact.


CONCLUSIONS
Early achievement of sustained RQ-PCR negativity appears to be a prerequisite for long-term hematologic complete remission in t(9;11)-positive AML. Furthermore, RQ-PCR might be useful for early detection of relapse. Additional patients need to be studied to corroborate these findings.
Scholl
Claudia
C
Department of Internal Medicine III, University Hospital of Ulm, Robert-Koch-Str. 8, 89081 Ulm, Germany.
Schlenk
Richard F
RF
Eiwen
Karina
K
Döhner
Hartmut
H
Fröhling
Stefan
S
Döhner
Konstanze
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics* / Q000648:ultrastructure; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D015337:Multicenter Studies as Topic; D051788:Myeloid-Lymphoid Leukemia Protein / Q000097:blood*; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000097:blood*; D036102:Peripheral Blood Stem Cell Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D014408:Biomarkers, Tumor; C474558:MLL-AF9 fusion protein, human; D015514:Oncogene Proteins, Fusion; D003561:Cytarabine; D051788:Myeloid-Lymphoid Leukemia Protein; D014212:Tretinoin; D005047:Etoposide; D008942:Mitoxantrone; D015255:Idarubicin