Synapse - Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia

Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia Journal Article

Authors:	Stahl, M.; Derkach, A.; Farnoud, N.; Bewersdorf, J. P.; Robinson, T.; Famulare, C.; Cho, C.; Devlin, S.; Menghrajani, K.; Patel, M. A.; Cai, S. F.; Miles, L. A.; Bowman, R. L.; Geyer, M. B.; Dunbar, A.; Epstein-Peterson, Z. D.; McGovern, E.; Schulman, J.; Glass, J. L.; Taylor, J.; Viny, A. D.; Stein, E. M.; Getta, B.; Arcila, M. E.; Gao, Q.; Barker, J.; Shaffer, B. C.; Papadopoulos, E. B.; Gyurkocza, B.; Perales, M. A.; Abdel-Wahab, O.; Levine, R. L.; Giralt, S. A.; Zhang, Y.; Xiao, W.; Pai, N.; Papaemmanuil, E.; Tallman, M. S.; Roshal, M.; Goldberg, A. D.
Article Title:	Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia
Abstract:	Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD− remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD− remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD− remission. Patients with fewer individual clones were more likely to achieve MRD− remission. Among 132 patients who underwent allo-SCT, outcomes were favorable whether patients achieved early MRD− after induction or later MRD− after subsequent therapy prior to allo-SCT. As MRD conversion with chemotherapy prior to allo-SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered. © 2022 Wiley Periodicals LLC.
Keywords:	transplantation, homologous; genetics; leukemia, myeloid, acute; stem cell transplantation; hematopoietic stem cell transplantation; minimal residual disease; neoplasm, residual; remission; remission induction; allotransplantation; acute myeloid leukemia; humans; prognosis; human
Journal Title:	American Journal of Hematology
Volume:	98
Issue:	1
ISSN:	0361-8609
Publisher:	John Wiley & Sons, Inc.
Date Published:	2023-01-01
Start Page:	79
End Page:	89
Language:	English
DOI:	10.1002/ajh.26757
PUBMED:	36251406
PROVIDER:	scopus
PMCID:	PMC10080561
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141588634&doi=10.1002%2fajh.26757&partnerID=40&md5=0a29c434e39b399fc02c758198eb75ee
Notes:	Article -- The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding author is MSK author Maximilian Stahl -- Export Date: 3 January 2023 -- Source: Scopus