Impact of trisomy 19 on outcome according to genetic makeup in patients with acute myeloid leukemia
Sabine Kayser,
David Martínez-Cuadrón,
Rebeca Rodriguez-Veiga,
Mathias Hänel,
Mar Tormo,
Kerstin Schäfer-Eckart,
Carmen Botella,
Friedrich Stölzel,
Teresa Bernal del Castillo,
Ulrich Keller,
Carlos Rodriguez-Medina,
Gerhard Held,
Maria-Luz Amigo,
Christoph Schliemann,
Mercedes Colorado,
Martin Kaufmann,
Manuel Barrios Garcia,
Stefan W. Krause,
Martin Görner,
Edgar Jost,
Björn Steffen,
Sven Zukunft,
Uwe Platzbecker,
Anthony D. Ho,
Claudia D. Baldus,
Hubert Serve,
Carsten Müller-Tidow,
Christian Thiede,
Martin Bornhäuser,
Pau Montesinos,
Christoph Röllig,
Richard F. Schlenk
Affiliations
Sabine Kayser
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany; NCT Trial Center, National Center of Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Clinic and Policlinic I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig
David Martínez-Cuadrón
Hematology Department, Hospital Universitari i Politècnic, La Fe, València, Spain; CIBERONC, Instituto Carlos III, Madrid
Rebeca Rodriguez-Veiga
Hematology Department, Hospital Universitari i Politècnic, La Fe, València
Mathias Hänel
Klinikum Chemnitz, Chemnitz
Mar Tormo
Hematology Department, Hospital Clínico Universitario, INCLIVA Research Institute, University of Valencia, Valencia
Kerstin Schäfer-Eckart
Hospital Nord, Nurnberg
Carmen Botella
Hospital General, Alicante
Friedrich Stölzel
Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden
Teresa Bernal del Castillo
Hospital Central de Asturias
Ulrich Keller
Department of Hematology, Oncology and Cancer Immunology, Charité-University Medical Center, Campus Benjamin Franklin, Berlin
Carlos Rodriguez-Medina
Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria
Gerhard Held
Westpfalz Klinikum, Kaiserslautern
Maria-Luz Amigo
Hospital General Universitario Morales Meseguer, Murcia
Christoph Schliemann
University Hospital Muenster, Muenster
Mercedes Colorado
Hospital Universitario Marqués de Valdecilla, Santander
Martin Kaufmann
Robert Bosch Hospital Stuttgart, Stuttgart
Manuel Barrios Garcia
Department of Hematology, Hospital Regional Universitario de Málaga, Málaga
Stefan W. Krause
Department of Internal Medicine 5 – Hematology/Oncology, University Hospital of Erlangen, Erlangen
Martin Görner
Klinik für Hämatologie, Onkologie und Palliativmedizin, Klinikum Bielefeld Mitte
Edgar Jost
Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, University Hospital RWTH Aachen, Aachen
Björn Steffen
Department of Internal Medicine II, University Hospital of Frankfurt Main
Sven Zukunft
Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden
Uwe Platzbecker
Medical Clinic and Policlinic I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig
Anthony D. Ho
Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg
Claudia D. Baldus
Department of Internal Medicine II, University Hospital of Kiel, Kiel Germany
Hubert Serve
Department of Internal Medicine II, University Hospital of Frankfurt Main
Carsten Müller-Tidow
Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg
Christian Thiede
Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden
Martin Bornhäuser
Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden
Pau Montesinos
Hematology Department, Hospital Universitari i Politècnic, La Fe, València, Spain; CIBERONC, Instituto Carlos III, Madrid
Christoph Röllig
Department of Medicine I, University Hospital Carl-Gustav-Carus, Dresden
Richard F. Schlenk
NCT Trial Center, National Center of Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany; Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg
We retrospectively studied 97 acute myeloid leukemia patients with trisomy 19 (median age at diagnosis 57 years; range, 17- 83 years) treated between 2001 and 2019 within two multicenter study groups. Trisomy 19 occurred alone in ten (10.5%) patients, with additional abnormalities being present in non-complex karyotypes in eight (8%) patients and in complex karyotypes in 79 (82%) patients. Altogether, karyotypes characterized by trisomies only were present in 27 (28%) patients. Data on response and outcome of intensively treated patients were available for 92 cases. The median follow-up was 6.4 years (95% confidence interval [95% CI]: 2.9-9.0 years). The complete remission (CR) rate after induction therapy was 52% (48 patients); the early death rate was 10% (n=9). Notably, patients with trisomy 19 as the sole abnormality had a CR rate of 89%. Allogeneic hematopoietic stem cell transplantation (allo-HCT) was performed in 34 (35%) patients (CR, n=19; active disease, n=15). Five-year relapse-free and overall survival rates were 26% (95% CI: 16-43%) and 20% (95% CI: 13-31%), respectively. Overall survival rates were significantly higher in patients with trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only (P=0.05). An Andersen-Gill model including allo-HCT as a time-dependent covariable on overall survival revealed that trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only was a favorable factor (hazard ratio [HR]=0.47; P=0.021); higher age at diagnosis had an adverse impact (10 years difference; HR=1.29; P=0.002), whereas allo-HCT did not have a beneficial impact (odds ratio=1.45; P=0.21). In our cohort, patients with trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only had a high CR rate and better clinical outcome.