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Allogeneic hematopoietic cell transplantation improves outcome of adults with t(6;9) acute myeloid leukemia: results from an international collaborative study

S. Kayser, RK. Hills, MR. Luskin, AM. Brunner, C. Terré, J. Westermann, K. Menghrajani, C. Shaw, MR. Baer, MA. Elliott, AE. Perl, Z. Ráčil, J. Mayer, P. Zak, T. Szotkowski, S. de Botton, D. Grimwade, K. Mayer, RB. Walter, A. Krämer, AK. Burnett,...

. 2020 ; 105 (1) : 161-169. [pub] 20190419

Language English Country Italy

Document type Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21020814

Grant support
K12 CA184746 NCI NIH HHS - United States
P30 CA008748 NCI NIH HHS - United States
P50 CA100632 NCI NIH HHS - United States

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.

Cardiff University School of Medicine Cardiff UK

Clinical Research Division Fred Hutchinson Cancer Research Center Seattle WA USA

Department of Epidemiology University of Washington Seattle WA USA

Department of Haematology Nottingham University Hospitals NHS Trust Nottingham UK

Department of Hemato Oncology Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Department of Hematology Oncology and Tumor Immunology Charité University Medical Center Campus Virchow Clinic Berlin Germany

Department of Internal Medicine 1 University Hospital Carl Gustav Carus Dresden Germany

Department of Internal Medicine 5 University Hospital of Heidelberg Heidelberg Germany

Department of Internal Medicine Hematology and Oncology Masaryk University and University Hospital Brno Brno Czech Republic

Department of Internal Medicine Hematology Faculty of Medicine Charles University and University Hospital Hradec Králové Hradec Králové Czech Republic

Department of Medical and Molecular Genetics King's College London Faculty of Life Sciences and Medicine London UK

Department of Medical Oncology Dana Farber Cancer Institute Boston MA USA

Department of Medicine University of Maryland School of Medicine Baltimore MD USA

Division of Hematology and Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA

Division of Hematology Department of Internal Medicine Mayo Clinic Rochester MN USA

Division of Hematology Department of Medicine University of Washington Seattle WA USA

German Cancer Research Center and Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany

Laboratory of Hematology André Mignot Hospital Le Chesnay France

Leukemia Service Department of Medicine Memorial Sloan Kettering Cancer Center Weill Cornell Medical College New York NY USA

Massachusetts General Hospital Boston MA USA

Medical Clinic 3 for Oncology Hematology and Rheumatology University Hospital Bonn Bonn Germany

Medical Clinic and Policlinic 1 Hematology and Cellular Therapy University Hospital Leipzig Leipzig Germany

NCT Trial Center National Center for Tumor Diseases Heidelberg Germany

Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD USA

Université Paris Saclay Gustave Roussy Villejuif France

University of Maryland Greenebaum Comprehensive Cancer Center Baltimore MD USA

References provided by Crossref.org

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$a 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.
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