Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3-internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Ali Bazarbachi,
Gesine Bug,
Frederic Baron,
Eolia Brissot,
Fabio Ciceri,
Iman Abou Dalle,
Hartmut Döhner,
Jordi Esteve,
Yngvar Floisand,
Sebastian Giebel,
Maria Gilleece,
Norbert-Claude Gorin,
Elias Jabbour,
Mahmoud Aljurf,
Hagop Kantarjian,
Mohamed Kharfan-Dabaja,
Myriam Labopin,
Francesco Lanza,
Florent Malard,
Zinaida Peric,
Thomas Prebet,
Farhad Ravandi,
Annalisa Ruggeri,
Jaime Sanz,
Christoph Schmid,
Roni Shouval,
Alexandros Spyridonidis,
Jurjen Versluis,
Norbert Vey,
Bipin N Savani,
Arnon Nagler,
Mohamad Mohty
Affiliations
Ali Bazarbachi
Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon;Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon
Gesine Bug
Department of Medicine 2, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
Frederic Baron
GIGA-I3, University and CHU of Liège, Liège, Belgium
Eolia Brissot
Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France
Fabio Ciceri
Vita-Salute San Raffaele University of Milan, Milan, ItalyHematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
Iman Abou Dalle
Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Hartmut Döhner
Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany
Jordi Esteve
Hematology Department, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcellona, Spain
Yngvar Floisand
Department of Hematology, Oslo University Hospital - Rikshospitalet, Oslo, Norway;Center for Cancer Cell Reprogramming, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway
Sebastian Giebel
Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute – Oncology Center, Gliwice Branch, Gliwice, Poland
Maria Gilleece
Department of Haematology, Leeds Teaching Hospitals Trust, Leeds, UK
Norbert-Claude Gorin
Department of Hematology and Cell Therapy, European Society for Blood and Marrow Transplantation, Paris Office, Hopital Saint-Antoine, Paris, France
Elias Jabbour
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Mahmoud Aljurf
Department of Hematology King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Hagop Kantarjian
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Mohamed Kharfan-Dabaja
Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapies Program, Mayo Clinic, Jacksonville, FL, USA
Myriam Labopin
Acute Leukemia Working Party, Paris Study Office, European Society for Blood and Marrow Transplantation, Paris, France;Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France
Francesco Lanza
Romagna Transplant Network, Ravenna, Italy
Florent Malard
Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France
Zinaida Peric
University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
Thomas Prebet
Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
Farhad Ravandi
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Annalisa Ruggeri
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children’s Hospital, Roma, ItalyEurocord, Hôpital Saint Louis, Paris, France
Jaime Sanz
Hematology Department, Hospital Universitari i Politecnic La Fe. Instituto de Investigación Sanitaria La Fe, Valencia, CIBERONC, Instituto Carlos III, Madrid, Spain
Christoph Schmid
Department of Hematology and Oncology, Augsburg University Hospital, Augsburg, Germany
Roni Shouval
Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Alexandros Spyridonidis
BMT Unit, University of Patras, Patras, Greece
Jurjen Versluis
Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands
Norbert Vey
Department of Hematology, Institut Paoli-Calmettes, Marseille, France
Bipin N Savani
Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
Arnon Nagler
Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Israel
Mohamad Mohty
Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France
The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in 25-30% of patients with acute myeloid leukemia (AML). Because of the poor prognosis associated with FLT3-internal tandem duplication mutated AML, allogeneic hematopoietic stem-cell transplantation (SCT) was commonly performed in first complete remission. Remarkable progress has been made in frontline treatments with the incorporation of FLT3 inhibitors and the development of highly sensitive minimal/measurable residual disease assays. Similarly, recent progress in allogeneic hematopoietic SCT includes improvement of transplant techniques, the use of haploidentical donors in patients lacking an HLA matched donor, and the introduction of FLT3 inhibitors as post-transplant maintenance therapy. Nevertheless, current transplant strategies vary between centers and differ in terms of transplant indications based on the internal tandem duplication allelic ratio and concomitant nucleophos-min-1 mutation, as well as in terms of post-transplant maintenance/consolidation. This review generated by international leukemia or transplant experts, mostly from the European Society for Blood and Marrow Transplantation, attempts to develop a position statement on best approaches for allogeneic hematopoietic SCT for AML with FLT3-internal tandem duplication including indications for and modalities of such transplants and on the potential optimization of post-transplant maintenance with FLT inhibitors.
