Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group

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Item Type:	Article
Title:	Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group
Creators Name:	Rücker, F.G., Agrawal, M., Corbacioglu, A., Weber, D., Kapp-Schwoerer, S., Gaidzik, V.I., Jahn, N., Schroeder, T., Wattad, M., Lübbert, M., Koller, E., Kindler, T., Götze, K., Ringhoffer, M., Westermann, J., Fiedler, W., Horst, H.A., Greil, R., Schroers, R., Mayer, K., Heinicke, T., Krauter, J., Schlenk, R.F., Thol, F., Heuser, M., Ganser, A., Bullinger, L., Paschka, P., Döhner, H. and Döhner, K.
Abstract:	We performed serial measurable residual disease (MRD) monitoring in bone marrow (BM) and peripheral blood (PB) samples of 155 intensively treated patients with RUNX1-RUNX1T1+ AML, using a qRT-PC-based assay with a sensitivity of up to 10-6. We assessed both reduction of RUNX1-RUNX1T1 transcript levels (TLs) and achievement of MRD negativity (MRD-) for impact on prognosis. Achievement of MR2.5 (>2.5 log reduction) after treatment cycle 1 and achievement of MR3.0 after treatment cycle 2 were significantly associated with a reduced risk of relapse (P = .034 and P = .028, respectively). After completion of therapy, achievement of MRD- in both BM and PB was an independent, favorable prognostic factor in cumulative incidence of relapse (4-year cumulative incidence relapse: BM, 17% vs 36%, P = .021; PB, 23% vs 55%, P = .001) and overall survival (4-year overall survival rate BM, 93% vs 70%, P = .007; PB, 87% vs 47%, P < .0001). Finally, during follow-up, serial qRT-PCR analyses allowed prediction of relapse in 77% of patients exceeding a cutoff value of 150 RUNX1-RUNX1T1 TLs in BM, and in 84% of patients exceeding a value of 50 RUNX1-RUNX1T1 TLs in PB. The KIT mutation was a significant factor predicting a lower CR rate and inferior outcome, but its prognostic impact was outweighed by RUNX1-RUNX1T1 TLs during treatment. Virtually all relapses occurred within 1 year after the end of treatment, with a very short latency from molecular to morphologic relapse, necessitating MRD assessment at short intervals during this time period. Based on our data, we propose a refined practical guideline for MRD assessment in RUNX1-RUNX1T1+ AML.
Keywords:	Acute Myeloid Leukemia, Core Binding Factor Alpha 2 Subunit, Fusion Oncogene Proteins, Genetic Translocation, Prognosis, RUNX1 Translocation Partner 1 Protein, Real-Time Polymerase Chain Reaction, Residual Neoplasm
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	134
Number:	19
Page Range:	1608-1618
Date:	7 November 2019
Official Publication:	https://doi.org/10.1182/blood.2019001425
PubMed:	View item in PubMed

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