Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state.
The inv(16) cytogenetic subtype of acute myeloid leukemia (AML) has a relatively good prognosis. Many patients achieve complete remission (CR). The prognostic uncertainty of negative qualitative reverse transcription-polymerase chain reaction (RT-PCR) assays suggests the need to identify prognostically significant critical thresholds by real-time RT-PCR. A reliable and sensitive (10(-5)) real-time RT-PCR assay was set up for the evaluation of relevant CBFbeta-MYH11/ABL transcript ratios and was applied to the 21 patients with inv(16) AML routinely referred for cytogenetic and molecular monitoring in Seràgnoli Institute (Bologna, Italy) since 1990. Among the 18 patients who underwent ablative chemotherapy, all achieved CR with a 3-year disease-free survival probability of 63% (95% CI, 40%-87%) and no recorded events after 26 months. Five patients had relapses; 2 died of disease and 3 entered second CR. Analysis of the 125 bone marrow (or peripheral blood) samples studied by real-time RT-PCR showed that transcript ratios of samples taken during CR at any time before a relapse were always greater than 0.12%, whereas those of samples taken during first or second CR from patients who did not subsequently have relapses were always less than 0.25%. This suggests that transcript ratios greater than 0.25% may correspond to high risk for relapse, whereas ratios below 0.12% might indicate the patient is in a curable state. If confirmed, such thresholds could open the way to a new phase in post-CR therapeutic decision making for patients with inv(16) AML.
Buonamici
Silvia
S
Institute of Hematology and Medical Oncology L. e A. Seràgnoli, University of Bologna, Italy.
Ottaviani
Emanuela
E
Testoni
Nicoletta
N
Montefusco
Vittorio
V
Visani
Giuseppe
G
Bonifazi
Francesca
F
Amabile
Marilina
M
Terragna
Carolina
C
Ruggeri
Deborah
D
Piccaluga
Pier Paolo
PP
Isidori
Alessandro
A
Malagola
Michele
M
Baccarani
Michele
M
Tura
Sante
S
Martinelli
Giovanni
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000235:genetics; D001856:Bone Marrow Examination; D016026:Bone Marrow Transplantation; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000648:ultrastructure*; D003131:Combined Modality Therapy; D003199:Computer Systems; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016313:Genes, abl; D006801:Humans; D007621:Karyotyping; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000097:blood / Q000235:genetics; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D016879:Salvage Therapy; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion