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Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation.
Pfeifer, Heike; Raum, Katharina; Markovic, Sandra; Nowak, Verena; Fey, Stephanie; Obländer, Julia; Pressler, Jovita; Böhm, Verena; Brüggemann, Monika; Wunderle, Lydia; Hüttmann, Andreas; Wäsch, Ralph; Beck, Joachim; Stelljes, Matthias; Viardot, Andreas; Lang, Fabian; Hoelzer, Dieter; Hofmann, Wolf-Karsten; Serve, Hubert; Weiss, Christel; Goekbuget, Nicola; Ottmann, Oliver G; Nowak, Daniel.
Afiliación
  • Pfeifer H; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
  • Raum K; Department of Hematology and Oncology and.
  • Markovic S; Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Nowak V; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
  • Fey S; Department of Hematology and Oncology and.
  • Obländer J; Department of Hematology and Oncology and.
  • Pressler J; Department of Hematology and Oncology and.
  • Böhm V; Department of Hematology and Oncology and.
  • Brüggemann M; Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • Wunderle L; Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
  • Hüttmann A; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
  • Wäsch R; Department of Hematology and Oncology, University Hospital Essen, Essen, Germany.
  • Beck J; Department of Hematology and Oncology, University Hospital Freiburg, Freiburg, Germany.
  • Stelljes M; Department of Hematology and Oncology, University Hospital Mainz, Mainz, Germany.
  • Viardot A; Department of Hematology and Oncology, University Hospital Münster, Münster, Germany.
  • Lang F; Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.
  • Hoelzer D; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
  • Hofmann WK; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
  • Serve H; Department of Hematology and Oncology and.
  • Weiss C; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
  • Goekbuget N; Department of Biomedical Statistics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; and.
  • Ottmann OG; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
  • Nowak D; Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
Blood ; 131(13): 1464-1475, 2018 03 29.
Article en En | MEDLINE | ID: mdl-29348129
We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)+ acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors (TKIs) and allogeneic stem cell transplantation (aSCT). Ninety-seven Ph+ ALL patients (median age 41 years; range 18-64 years) within the prospective multicenter German Multicenter ALL Study Group studies 06/99 (n = 8) and 07/2003 (n = 89) were analyzed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with single nucleotide polymorphism arrays and validated by multiplex ligation-dependent probe amplification. The frequencies of recurrently deleted genes were: IKZF1, 76%; CDKN2A/2B, 45%; PAX5, 43%; BTG1, 18%; EBF1, 13%; ETV6, 5%; RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a negative impact on all endpoints: overall survival (P = .023), disease-free survival (P = .012), and remission duration (P = .036). The negative predictive value of CDKN2A/2B deletions was retained in multivariable analysis along with other factors such as timing of TKI therapy, intensity of conditioning, achieving remission after induction phase 1 and BTG1 deletions. We therefore conclude that acquired genomic CDKN2A/2B deletions identify a subgroup of Ph+ ALL patients, who have an inferior prognosis despite aSCT in CR1. Their poor outcome was attributable primarily to a high relapse rate after aSCT.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cromosoma Filadelfia / Eliminación de Gen / Trasplante de Células Madre Hematopoyéticas / Acondicionamiento Pretrasplante / Inhibidor p16 de la Quinasa Dependiente de Ciclina / Inhibidores de Proteínas Quinasas / Inhibidor p15 de las Quinasas Dependientes de la Ciclina / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Blood Año: 2018 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cromosoma Filadelfia / Eliminación de Gen / Trasplante de Células Madre Hematopoyéticas / Acondicionamiento Pretrasplante / Inhibidor p16 de la Quinasa Dependiente de Ciclina / Inhibidores de Proteínas Quinasas / Inhibidor p15 de las Quinasas Dependientes de la Ciclina / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Blood Año: 2018 Tipo del documento: Article