The prognostic value of MLL-AF9 detection in patients with t(9;11)(p22;q23)-positive acute myeloid leukemia.

Abstract

BACKGROUND AND OBJECTIVES:

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.

DESIGN AND 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.

INTERPRETATION AND 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.

• Authors: Claudia Scholl, Richard F Schlenk, Karina Eiwen, Hartmut Döhner, Stefan Fröhling, Konstanze Döhner, AML Study Group
• Journal: Haematologica (Haematologica) Vol. 90 Issue 12 Pg. 1626-34 (Dec 2005) ISSN: 1592-8721 [Electronic] Italy
• PMID: 16330435 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• MLL-AF9 fusion protein, human
• Oncogene Proteins, Fusion
• Cytarabine
• Myeloid-Lymphoid Leukemia Protein
• Tretinoin
• Etoposide
• Mitoxantrone
• Idarubicin

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Biomarkers, Tumor (blood)
• Chromosomes, Human, Pair 11 (genetics, ultrastructure)
• Chromosomes, Human, Pair 9 (genetics, ultrastructure)
• Cohort Studies
• Combined Modality Therapy
• Cytarabine (administration & dosage)
• Etoposide (administration & dosage)
• Humans
• Idarubicin (administration & dosage)
• Leukemia, Myeloid (blood, drug therapy, genetics, mortality, pathology, surgery)
• Middle Aged
• Mitoxantrone (administration & dosage)
• Multicenter Studies as Topic
• Myeloid-Lymphoid Leukemia Protein (blood)
• Neoplasm, Residual
• Oncogene Proteins, Fusion (blood)
• Peripheral Blood Stem Cell Transplantation
• Polymerase Chain Reaction (methods)
• Prognosis
• Randomized Controlled Trials as Topic
• Recurrence
• Remission Induction
• Survival Analysis
• Translocation, Genetic
• Treatment Outcome
• Tretinoin (administration & dosage)