TY - JOUR
T1 - Post-induction MRD by FCM and GATA1-PCR are significant prognostic factors for myeloid leukemia of Down syndrome
AU - Taga, Takashi
AU - Tanaka, Shiro
AU - Hasegawa, Daisuke
AU - Terui, Kiminori
AU - Toki, Tsutomu
AU - Iwamoto, Shotaro
AU - Hiramatsu, Hidefumi
AU - Miyamura, Takako
AU - Hashii, Yoshiko
AU - Moritake, Hiroshi
AU - Nakayama, Hideki
AU - Takahashi, Hiroyuki
AU - Shimada, Akira
AU - Taki, Tomohiko
AU - Ito, Etsuro
AU - Hama, Asahito
AU - Ito, Masafumi
AU - Koh, Katsuyoshi
AU - Hasegawa, Daiichiro
AU - Saito, Akiko M.
AU - Adachi, Souichi
AU - Tomizawa, Daisuke
N1 - Funding Information:
Acknowledgements The authors deeply appreciate the invaluable cooperation of the large number of physicians working at the institutions, central diagnostic laboratories, and the office and data center of the JPLSG. We also wish to thank Dario Campana and Elaine Coustan-Smith (National University of Singapore) for helpful discussions regarding FCM-MRD analysis. This work was supported by a Grant for Clinical Cancer Research and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour, and Welfare of Japan. This work was supported in part by the Project Promoting Clinical Trials for Development of New Drugs (JP19lk0201061t0004) and Practical Research for Innovative Cancer Control (JP19ck0106329) from the Japan Agency for Medical Research and Development (AMED) and by Grants-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (KAKENHI: 26253061, 18H04039).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
PY - 2021/9
Y1 - 2021/9
N2 - Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 95.0% and 96.7% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 98.1% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD with EFS were 14.67 (p = 0.01). Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.
AB - Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 95.0% and 96.7% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 98.1% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD with EFS were 14.67 (p = 0.01). Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.
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U2 - 10.1038/s41375-021-01157-w
DO - 10.1038/s41375-021-01157-w
M3 - Article
C2 - 33589754
AN - SCOPUS:85100852857
SN - 0887-6924
VL - 35
SP - 2508
EP - 2516
JO - Leukemia
JF - Leukemia
IS - 9
ER -
