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Ferrata Storti Foundation
Haematologica 2018 Volume 104(7):1378-1387
Acute Myeloid Leukemia
Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute
myeloid leukemia
Wenbin Xiao,1 Aaron D. Goldberg,2 Christopher A. Famulare,3 Sean M. Devlin,4 Nghia T. Nguyen,1 Sinnifer Sim,1 Charlene C. Kabel,5 Minal A. Patel,3
Erin M. McGovern,3 Akshar Patel,3 Jessica Schulman,3 Andrew J. Dunbar,2
222 Zachary D. Epstein-Peterson, Kamal N. Menghrajani, Bartlomiej M. Getta,
Sheng F. Cai,2 Mark B. Geyer,2,6 Jacob L. Glass,2 Justin Taylor,2 Aaron D. Viny,2 Ross L. Levine,2,3,7 Yanming Zhang,8 Sergio A. Giralt,9 Virginia Klimek,2 Martin S. Tallman2 and Mikhail Roshal1
1Department of Pathology, Hematopathology Diagnostic Service; 2Department of Medicine, Leukemia Service; 3Center for Hematologic Malignancies; 4Epidemiology and Biostatistics; 5Clinical Pharmacy; 6Center for Cell Engineering; 7Human Oncology and Pathogenesis Program; 8Department of Pathology, Cytogenetics Laboratory and 9Department of Medicine, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
ABSTRACT
Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia (AML). Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. The European LeukemiaNet working party recently came to a consensus recommendation incorporating leukemia associated immunophenotype-based different from normal approach by multi-color flow cytometry for measurable residual disease evaluation. However, the analytical approach is highly expertise-dependent and diffi- cult to standardize. Here we demonstrate that loss of plasmacytoid dendrit- ic cell differentiation after 7+3 induction in AML is highly specific for meas- urable residual disease positivity (specificity 97.4%) in a uniformly treated patient cohort. Moreover, loss of plasmacytoid dendritic cell differentiation as determined by a blast-to-plasmacytoid dendritic cell ratio >10 was strongly associated with inferior overall and relapse-free survival (RFS) [Hazard ratio 2.79, 95% confidence interval (95%CI): 0.98-7.97; P=0.077) and 3.83 (95%CI: 1.51-9.74; P=0.007), respectively), which is similar in magnitude to measurable residual disease positivity. Importantly, measura- ble residual disease positive patients who reconstituted plasmacytoid den- dritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) showed a higher rate of measurable residual disease clearance at later pre- transplant time points compared to patients with loss of plasmacytoid den- dritic cell differentiation (blast/ plasmacytoid dendritic cell ratio <10) (6 of 12, 50% vs. 2 of 18, 11%; P=0.03). Furthermore pre-transplant plasmacytoid dendritic cell recovery was associated with superior outcome in measurable residual disease positive patients. Our study provides a novel, simple, broadly applicable, and quantitative multi-color flow cytometry approach to risk stratification in AML.
Correspondence:
WENBIN XIAO
xiaow@mskcc.org
MIKHAIL ROSHAL
roshalm@mskcc.org
Received: July 25, 2018. Accepted: December 4, 2018. Pre-published: December 6, 2018.
doi:10.3324/haematol.2018.203018
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/7/1378
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