Prognostic impact of the adverse molecular-genetic profile on long-term outcomes following allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 8; pp. 1908 - 1918
• Main Authors: Daher-Reyes, Georgina, Kim, TaeHyung, Novitzky-Basso, Igor, Kim, Kyuoung Ha, Smith, Adam, Stockley, Tracy, Capochichi, Jose-Mario, Al-Shaibani, Zeyad, Pasic, Ivan, Law, Arjun, Lam, Wilson, Michelis, Fotios V., Gerbitz, Armin, Viswabandya, Auro, Lipton, Jeffrey, Kumar, Rajat, Mattsson, Jonas, Schimmer, Aaron, McNamara, Caroline, Murphy, Tracy, Maze, Dawn, Gupta, Vikas, Sibai, Hassan, Chan, Steven, Yee, Karen, Minden, Mark, Zhang, Zhaolei, Schuh, Andre, Kim, Dennis D. H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2021; Nature Publishing Group
• Subjects: 45; 692/308/2056; 692/499; 692/699/1541/1990/283/1897; Abnormalities; Acute myeloid leukemia; Cell Biology; Cytogenetics; Gene deletion; Gene mutations; Genetic abnormalities; Genetic analysis; Genetic aspects; Health aspects; Hematology; Hematopoietic stem cells; Internal Medicine; Karyotypes; Leukemia; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Monosomy; Multivariate analysis; Mutation; Myeloid leukemia; Next-generation sequencing; p53 Protein; Prognosis; Public Health; Runx1 protein; Stem cell transplantation; Stem Cells; Survival; Transplantation; Trisomy; Canada
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/s41409-021-01255-4

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).