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TP53 and IDH2 Somatic Mutations Are Associated With Inferior Overall Survival After Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome.
Kharfan-Dabaja, Mohamed A; Komrokji, Rami S; Zhang, Qing; Kumar, Ambuj; Tsalatsanis, Athanasios; Perkins, Janelle; Nishihori, Taiga; Field, Teresa; Al Ali, Najla; Mishra, Asmita; Sallman, David; Salem, Karma Z; Zhang, Ling; Moscinski, Lynn; Fernandez, Hugo F; Lancet, Jeffrey; List, Alan; Anasetti, Claudio; Padron, Eric.
Afiliación
  • Kharfan-Dabaja MA; Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL. Electronic address: Mohamed.Kharfan-Dabaja@Moffitt.org.
  • Komrokji RS; Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
  • Zhang Q; Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
  • Kumar A; University of South Florida Health Program for Comparative Effectiveness Research, Tampa, FL.
  • Tsalatsanis A; University of South Florida Health Program for Comparative Effectiveness Research, Tampa, FL.
  • Perkins J; College of Pharmacy, University of South Florida, Tampa, FL.
  • Nishihori T; Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
  • Field T; Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
  • Al Ali N; Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
  • Mishra A; Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
  • Sallman D; Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
  • Salem KZ; Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
  • Zhang L; Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center, Tampa, FL.
  • Moscinski L; Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center, Tampa, FL.
  • Fernandez HF; Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
  • Lancet J; Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
  • List A; Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
  • Anasetti C; Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
  • Padron E; Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL.
Clin Lymphoma Myeloma Leuk ; 17(11): 753-758, 2017 11.
Article en En | MEDLINE | ID: mdl-28687222
BACKGROUND: Next-generation sequencing has identified somatic mutations that are prognostic of cancer. PATIENTS AND METHODS: We evaluated the incidence and prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS) patients who received an allogeneic hematopoietic cell transplantation. Next-generation sequencing was performed on paraffin embedded bone marrow, which was obtained at a median of 31 days before initiating the preparative regimen. RESULTS: The 3 most common subtypes of MDS were refractory anemia with excess blasts (RAEB)-1 (35%), RAEB-2 (29%), and refractory cytopenia with multilineage dysplasia (18%). Most patients (91%) received a myeloablative regimen of fludarabine with intravenous busulfan. Somatic mutations (> 0) were identified in 39 (44%) of analyzed samples. The 6 most commonly identified gene mutations were ASXL1 (8%), DNMT3A (8%), RUNX1 (7%), KRAS (6%), IDH2 (4%), and TP53 (4%). The low incidence of mutations in our study sample might be explained by tissue source and stringent variant-calling methodology. Moreover, we speculate that the low incidence of mutations might, perhaps, also be explained by previous azacitidine treatment in 82% of cases. Multivariate analysis identified TP53 (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.12-13.09; P = .03) and IDH2 mutations (HR, 4.74; 95% CI, 1.33-16.91; P = .02) as predictors of inferior 3-year overall survival. CONCLUSION: This study furthers implementation of clinical genomics in MDS and identifies TP53 and IDH2 as targets for pre- or post-transplant therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante Homólogo / Síndromes Mielodisplásicos / Proteína p53 Supresora de Tumor / Trasplante de Células Madre Hematopoyéticas / Acondicionamiento Pretrasplante / Isocitrato Deshidrogenasa Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Lymphoma Myeloma Leuk Asunto de la revista: NEOPLASIAS Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante Homólogo / Síndromes Mielodisplásicos / Proteína p53 Supresora de Tumor / Trasplante de Células Madre Hematopoyéticas / Acondicionamiento Pretrasplante / Isocitrato Deshidrogenasa Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Lymphoma Myeloma Leuk Asunto de la revista: NEOPLASIAS Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos