Next-generation sequencing–based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse
| Autor: | Ja-Yeon Lee, Hyeoung-Joon Kim, Seunghyun Choi, Sung-Hoon Jung, Je-Jung Lee, Seung-Shin Lee, Yeo-Kyeoung Kim, Seo-Yeon Ahn, Myung-Geun Shin, Seong-Kyu Park, Joon Ho Moon, Marc S. Tyndel, Dennis Dong Hwan Kim, Sang Kyun Sohn, Deok-Hwan Yang, Zhaolei Zhang, Jae-Sook Ahn, TaeHyung Kim, Yoo Jin Lee |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Myeloid Adolescent medicine.medical_treatment Immunology Hematopoietic stem cell transplantation Biochemistry Young Adult 03 medical and health sciences 0302 clinical medicine Risk Factors hemic and lymphatic diseases Internal medicine medicine Humans Chemotherapy business.industry Incidence (epidemiology) Hazard ratio Hematopoietic Stem Cell Transplantation High-Throughput Nucleotide Sequencing Myeloid leukemia Cell Biology Hematology Middle Aged medicine.disease Transplantation Leukemia Myeloid Acute Leukemia medicine.anatomical_structure 030220 oncology & carcinogenesis Mutation Female Neoplasm Recurrence Local business 030215 immunology |
| Zdroj: | Blood. 132:1604-1613 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2018-04-848028 |
| Popis: | Next-generation sequencing (NGS) has been applied to define clinically relevant somatic mutations and classify subtypes in acute myeloid leukemia (AML). Persistent allelic burden after chemotherapy is associated with higher relapse incidence, but presence of allelic burden in AML patients after receiving allogeneic hematopoietic cell transplantation (HCT) has not been examined longitudinally. As such, we aimed to assess the feasibility of NGS in monitoring AML patients receiving HCT. Using a targeted gene panel, we performed NGS in 104 AML patients receiving HCT using samples collected at diagnosis, pre-HCT, and post-HCT at day 21 (post-HCTD21). NGS detected 256 mutations in 90 of 104 patients at diagnosis, which showed stepwise clearances after chemotherapy and HCT. In a subset of patients, mutations were still detectable pre-HCT and post-HCT. Most post-HCT mutations originate from mutations initially detected at diagnosis. Post-HCTD21 allelic burdens in relapsed patients were higher than in nonrelapsed patients. Post-HCTD21 mutations in relapsed patients all expanded at relapse. Assessment of variant allele frequency (VAF) revealed that overall VAF post-HCTD21 (VAF0.2%-post-HCTD21) is associated with an increased risk of relapse (56.2% vs 16.0% at 3 years; P < .001) and worse overall survival (OS; 36.5% vs 67.0% at 3 years; P = .006). Multivariate analyses confirmed that VAF0.2%-post-HCTD21 is an adverse prognostic factor for OS (hazard ratio [HR], 3.07; P = .003) and relapse incidence (HR, 4.75; P < .001), independent of the revised European LeukemiaNet risk groups. Overall, current study demonstrates that NGS-based posttransplant monitoring in AML patients is feasible and can distinguish high-risk patients for relapse. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|