Prognostic impact of the adverse molecular-genetic profile on long-term outcomes following allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia
| Autor: | Wilson Lam, Caroline J McNamara, Dennis Dong Hwan Kim, TaeHyung Kim, Jonas Mattsson, Zhaolei Zhang, Hassan Sibai, Rajat Kumar, Armin Gerbitz, Steven M. Chan, Karen W.L. Yee, Jose Mario Capo-Chichi, Tracy Murphy, Dawn Maze, Georgina S. Daher-Reyes, Andre C. Schuh, Aaron D. Schimmer, Igor Novitzky-Basso, Arjun Law, Tracy Stockley, Kyuoung Ha Kim, Jeffrey H. Lipton, Zeyad Al-Shaibani, Mark D. Minden, Adam C. Smith, Ivan Pasic, Fotios V. Michelis, Auro Viswabandya, Vikas Gupta |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
Chromosome 7 (human) Transplantation medicine.medical_specialty NPM1 Univariate analysis business.industry medicine.medical_treatment Myeloid leukemia Hematology Hematopoietic stem cell transplantation Trisomy 8 medicine.disease 03 medical and health sciences Haematopoiesis 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine Complex Karyotype medicine business 030215 immunology |
| Zdroj: | Bone Marrow Transplantation. 56:1908-1918 |
| ISSN: | 1476-5365 0268-3369 |
| Popis: | The impact of adverse risk genetic profiles on outcomes in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HCT) has not been fully elucidated. Accordingly, we have profiled somatic mutations at diagnosis using next-generation sequencing (NGS) in 178 AML patients who received allogeneic HCT. NGS revealed 598 somatic mutations in 165/178 patients (92.7%). Frequently mutated genes include DNMT3A, TET2, NPM1, RUNX1, IDH2, and FLT3. Commonly detected cytogenetic profiles include normal karyotype, trisomy 8, monosomal karyotype (MK), deletion 5, complex karyotype (CK), and monosomy 7. In univariate analyses, TP53 mutation, MK, CK, and monosomy 7 were associated with decreased overall survival (OS), relapse-free survival (RFS), and a higher relapse incidence (RI). We defined adverse molecular-genetic profile as harboring at least one of the molecular/genetic abnormalities of TP53 mutation, MK, CK, monosomy 7, and deletion 5. The patients harboring adverse molecular-genetic profile (n = 30) showed a lower 2-year OS (24.9% vs. 57.9%; p = 0.003), RFS (23.7% vs. 57.9%; p = 0.002), and higher RI (47.2% and 17.2%; p = 0.001) after HCT when compared to patients without those lesions. Multivariate analysis confirmed adverse molecular-genetic profile as an independent prognostic factor, associated with decreased OS (HR 2.19), RFS (HR 2.23), and higher RI (HR 2.94). |
| Databáze: | OpenAIRE |
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