TY - JOUR
T1 - Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem-cell transplantation
AU - Della Porta, Matteo G.
AU - Gallì, Anna
AU - Bacigalupo, Andrea
AU - Zibellini, Silvia
AU - Bernardi, Massimo
AU - Rizzo, Ettore
AU - Allione, Bernardino
AU - Van Lint, Maria Teresa
AU - Pioltelli, Pietro
AU - Marenco, Paola
AU - Bosi, Alberto
AU - Voso, Maria Teresa
AU - Sica, Simona
AU - Cuzzola, Mariella
AU - Angelucci, Emanuele
AU - Rossi, Marianna
AU - Ubezio, Marta
AU - Malovini, Alberto
AU - Limongelli, Ivan
AU - Ferretti, Virginia V.
AU - Spinelli, Orietta
AU - Tresoldi, Cristina
AU - Pozzi, Sarah
AU - Luchetti, Silvia
AU - Pezzetti, Laura
AU - Catricalà, Silvia
AU - Milanesi, Chiara
AU - Riva, Alberto
AU - Bruno, Benedetto
AU - Ciceri, Fabio
AU - Bonifazi, Francesca
AU - Bellazzi, Riccardo
AU - Papaemmanuil, Elli
AU - Santoro, Armando
AU - Alessandrino, Emilio P.
AU - Rambaldi, Alessandro
AU - Cazzola, Mario
PY - 2016
Y1 - 2016
N2 - Purpose: The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various combinations of somatic mutations are associated with different clinical phenotypes and outcomes. Whether the genetic basis of MDS influences the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) is unclear. Patients and Methods: We studied 401 patients with MDS or acute myeloid leukemia (AML) evolving from MDS (MDS/AML). We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. We then analyzed the impact of mutations on the outcome of HSCT. Results: Overall, 87% of patients carried one or more oncogenic mutations. Somatic mutations of ASXL1, RUNX1, and TP53 were independent predictors of relapse and overall survival after HSCT in both patients with MDS and patients with MDS/AML (P values ranging from.003 to.035). In patients with MDS/AML, gene ontology (ie, secondary-type AML carrying mutations in genes of RNA splicing machinery, TP53-mutated AML, or de novo AML) was anindependent predictor of posttransplantation outcome (P =.013). The impact of ASXL1, RUNX1, and TP53 mutations on posttransplantation survival was independent of the revised International Prognostic Scoring System (IPSS-R). Combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Accounting for various combinations of IPSS-R risk and somatic mutations, the 5-year probability of survival after HSCT ranged from 0% to 73%. Conclusion: Somatic mutation in ASXL1, RUNX1, or TP53 is independently associated with unfavorable outcomes and shorter survival after allogeneic HSCT for patients with MDS and MDS/AML. Accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.
AB - Purpose: The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various combinations of somatic mutations are associated with different clinical phenotypes and outcomes. Whether the genetic basis of MDS influences the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) is unclear. Patients and Methods: We studied 401 patients with MDS or acute myeloid leukemia (AML) evolving from MDS (MDS/AML). We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. We then analyzed the impact of mutations on the outcome of HSCT. Results: Overall, 87% of patients carried one or more oncogenic mutations. Somatic mutations of ASXL1, RUNX1, and TP53 were independent predictors of relapse and overall survival after HSCT in both patients with MDS and patients with MDS/AML (P values ranging from.003 to.035). In patients with MDS/AML, gene ontology (ie, secondary-type AML carrying mutations in genes of RNA splicing machinery, TP53-mutated AML, or de novo AML) was anindependent predictor of posttransplantation outcome (P =.013). The impact of ASXL1, RUNX1, and TP53 mutations on posttransplantation survival was independent of the revised International Prognostic Scoring System (IPSS-R). Combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Accounting for various combinations of IPSS-R risk and somatic mutations, the 5-year probability of survival after HSCT ranged from 0% to 73%. Conclusion: Somatic mutation in ASXL1, RUNX1, or TP53 is independently associated with unfavorable outcomes and shorter survival after allogeneic HSCT for patients with MDS and MDS/AML. Accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.
KW - Cancer Research
KW - Oncology
KW - Cancer Research
KW - Oncology
UR - http://hdl.handle.net/10807/92654
UR - http://jco.ascopubs.org/content/34/30/3627.full.pdf+html
U2 - 10.1200/JCO.2016.67.3616
DO - 10.1200/JCO.2016.67.3616
M3 - Article
SN - 0732-183X
VL - 34
SP - 3627
EP - 3637
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
ER -