Allogeneic hematopoietic cell transplantation improves outcome of adults with t(6;9) acute myeloid leukemia: results from an international collaborative study
Sabine Kayser,
Robert K. Hills,
Marlise R. Luskin,
Andrew M. Brunner,
Christine Terré,
Jörg Westermann,
Kamal Menghrajani,
Carole Shaw,
Maria R. Baer,
Michelle A. Elliott,
Alexander E. Perl,
Zdeněk Ráčil,
Jiri Mayer,
Pavel Zak,
Tomas Szotkowski,
Stéphane de Botton,
David Grimwade,
Karin Mayer,
Roland B. Walter,
Alwin Krämer,
Alan K. Burnett,
Anthony D. Ho,
Uwe Platzbecker,
Christian Thiede,
Gerhard Ehninger,
Richard M. Stone,
Christoph Röllig,
Martin S. Tallman,
Elihu H. Estey,
Carsten Müller-Tidow,
Nigel H. Russell,
Richard F. Schlenk,
Mark J. Levis
Affiliations
Sabine Kayser
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany;German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
Robert K. Hills
Cardiff University School of Medicine, Cardiff, UK
Marlise R. Luskin
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Andrew M. Brunner
Massachusetts General Hospital, Boston, MA, USA
Christine Terré
Laboratory of Hematology, André Mignot Hospital, Le Chesnay, France
Jörg Westermann
Department of Hematology, Oncology and Tumor Immunology, Charité-University Medical Center, Campus Virchow Clinic, Berlin, Germany
Kamal Menghrajani
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA
Carole Shaw
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Hematology/Department of Medicine, University of Washington, Seattle, WA, USA
Maria R. Baer
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA;Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
Michelle A. Elliott
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
Alexander E. Perl
Division of Hematology and Oncology, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Zdeněk Ráčil
Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic
Jiri Mayer
Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic
Pavel Zak
4th Department of Internal Medicine-Hematology, Faculty of Medicine, Charles University and University Hospital Hradec Králové, Hradec Králové, Czech Republic
Tomas Szotkowski
Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
Stéphane de Botton
Université Paris-Saclay, Gustave Roussy Villejuif, France
David Grimwade
Department of Medical & Molecular Genetics, King’s College London, Faculty of Life Sciences and Medicine, London, UK
Karin Mayer
Medical Clinic III for Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany
Roland B. Walter
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Hematology/Department of Medicine, University of Washington, Seattle, WA, USA;Department of Epidemiology, University of Washington, Seattle, WA, USA
Alwin Krämer
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany;German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
Alan K. Burnett
Cardiff University School of Medicine, Cardiff, UK
Anthony D. Ho
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany
Uwe Platzbecker
Medical Clinic and Policlinic I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
Christian Thiede
Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany
Gerhard Ehninger
Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany
Richard M. Stone
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Christoph Röllig
Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany
Martin S. Tallman
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA
Elihu H. Estey
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Division of Hematology/Department of Medicine, University of Washington, Seattle, WA, USA
Carsten Müller-Tidow
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany
Nigel H. Russell
Department of Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK
Richard F. Schlenk
NCT Trial Center, National Center for Tumor Diseases, Heidelberg, Germany
Mark J. Levis
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Acute myeloid leukemia (AML) with t(6;9)(p22;q34) is a distinct entity accounting for 1-2% of AML cases. A substantial proportion of these patients have a concomitant FLT3-ITD. While outcomes are dismal with intensive chemotherapy, limited evidence suggests allogeneic hematopoietic cell transplantation (allo-HCT) may improve survival if performed early during first complete remission. We report on a cohort of 178 patients with t(6;9)(p22;q34) within an international, multicenter collaboration. Median age was 46 years (range: 16-76), AML was de novo in 88%, FLT3-ITD was present in 62%, and additional cytogenetic abnormalities in 21%. Complete remission was achieved in 81% (n=144), including 14 patients who received high-dose cytarabine after initial induction failure. With a median follow up of 5.43 years, estimated overall survival at five years was 38% (95%CI: 31-47%). Allo-HCT was performed in 117 (66%) patients, including 89 in first complete remission. Allo-HCT in first complete remission was associated with higher 5-year relapse-free and overall survival as compared to consolidation chemotherapy: 45% (95%CI: 35-59%) and 53% (95%CI: 42-66%) versus 7% (95%CI: 3-19%) and 23% (95%CI: 13-38%), respectively. For patients undergoing allo-HCT, there was no difference in overall survival rates at five years according to whether it was performed in first [53% (95%CI: 42-66%)], or second [58% (95%CI: 31-100%); n=10] complete remission or with active disease/relapse [54% (95%CI: 34-84%); n=18] (P=0.67). Neither FLT3-ITD nor additional chromosomal abnormalities impacted survival. In conclusion, outcomes of t(6;9)(p22;q34) AML are poor with chemotherapy, and can be substantially improved with allo-HCT.