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

Silvia Buonamici, Emanuela Ottaviani, Nicoletta Testoni, Vittorio Montefusco, Giuseppe Visani, Francesca Bonifazi, Marilina Amabile, Carolina Terragna, Deborah Ruggeri, Pier Paolo Piccaluga, Alessandro Isidori, Michele Malagola, Michele Baccarani, Sante Tura, Giovanni Martinelli

Research output: Contribution to journalArticle

Abstract

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 CBFβ-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% Cl, 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.

Original languageEnglish
Pages (from-to)443-449
Number of pages7
JournalBlood
Volume99
Issue number2
DOIs
Publication statusPublished - Jan 15 2002

ASJC Scopus subject areas

  • Hematology

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    Buonamici, S., Ottaviani, E., Testoni, N., Montefusco, V., Visani, G., Bonifazi, F., Amabile, M., Terragna, C., Ruggeri, D., Piccaluga, P. P., Isidori, A., Malagola, M., Baccarani, M., Tura, S., & Martinelli, G. (2002). 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. Blood, 99(2), 443-449. https://doi.org/10.1182/blood.V99.2.443