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

doi:10.3324/haematol.2019.243410

Review

. 2020 Jun;105(6):1507-1516.

doi: 10.3324/haematol.2019.243410. Epub 2020 Apr 2.

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^{1

2}, Gesine Bug³, Frederic Baron⁴, Eolia Brissot⁵, Fabio Ciceri⁶, Iman Abou Dalle⁷, Hartmut Döhner⁸, Jordi Esteve⁹, Yngvar Floisand^{10

11}, Sebastian Giebel¹², Maria Gilleece¹³, Norbert-Claude Gorin¹⁴, Elias Jabbour¹⁵, Mahmoud Aljurf¹⁶, Hagop Kantarjian¹⁵, Mohamed Kharfan-Dabaja¹⁷, Myriam Labopin^{18

5}, Francesco Lanza¹⁹, Florent Malard⁵, Zinaida Peric²⁰, Thomas Prebet²¹, Farhad Ravandi¹⁵, Annalisa Ruggeri²², Jaime Sanz²³, Christoph Schmid²⁴, Roni Shouval²⁵, Alexandros Spyridonidis²⁶, Jurjen Versluis²⁷, Norbert Vey²⁸, Bipin N Savani²⁹, Arnon Nagler³⁰, Mohamad Mohty⁵

Affiliations

¹ Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon bazarbac@aub.edu.lb.
² Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon.
³ Department of Medicine 2, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.
⁴ GIGA-I3, University and CHU of Liège, Liège, Belgium.
⁵ Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France.
⁶ Vita-Salute San Raffaele University of Milan, Milan, ItalyHematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁷ Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
⁸ Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany.
⁹ Hematology Department, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcellona, Spain.
¹⁰ Department of Hematology, Oslo University Hospital - Rikshospitalet, Oslo, Norway.
¹¹ Center for Cancer Cell Reprogramming, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.
¹² Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.
¹³ Department of Haematology, Leeds Teaching Hospitals Trust, Leeds, UK.
¹⁴ Department of Hematology and Cell Therapy, European Society for Blood and Marrow Transplantation, Paris Office, Hopital Saint-Antoine, Paris, France.
¹⁵ Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁶ Department of Hematology King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
¹⁷ Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapies Program, Mayo Clinic, Jacksonville, FL, USA.
¹⁸ Acute Leukemia Working Party, Paris Study Office, European Society for Blood and Marrow Transplantation, Paris, France.
¹⁹ Romagna Transplant Network, Ravenna, Italy.
²⁰ University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia.
²¹ Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
²² Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Roma, ItalyEurocord, Hôpital Saint Louis, Paris, France.
²³ Hematology Department, Hospital Universitari i Politecnic La Fe. Instituto de Investigación Sanitaria La Fe, Valencia, CIBERONC, Instituto Carlos III, Madrid, Spain.
²⁴ Department of Hematology and Oncology, Augsburg University Hospital, Augsburg, Germany.
²⁵ Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁶ BMT Unit, University of Patras, Patras, Greece.
²⁷ Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands.
²⁸ Department of Hematology, Institut Paoli-Calmettes, Marseille, France.
²⁹ Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
³⁰ Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Israel.

PMID: 32241850
PMCID: PMC7271578
DOI: 10.3324/haematol.2019.243410

Review

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 et al. Haematologica. 2020 Jun.

. 2020 Jun;105(6):1507-1516.

doi: 10.3324/haematol.2019.243410. Epub 2020 Apr 2.

Authors

Affiliations

¹ Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon bazarbac@aub.edu.lb.
² Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon.
³ Department of Medicine 2, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.
⁴ GIGA-I3, University and CHU of Liège, Liège, Belgium.
⁵ Sorbonne Universités, UPMC University of Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), Hematology Department, AP-HP, Saint Antoine Hospital, Paris, France.
⁶ Vita-Salute San Raffaele University of Milan, Milan, ItalyHematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁷ Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
⁸ Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany.
⁹ Hematology Department, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Barcellona, Spain.
¹⁰ Department of Hematology, Oslo University Hospital - Rikshospitalet, Oslo, Norway.
¹¹ Center for Cancer Cell Reprogramming, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.
¹² Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.
¹³ Department of Haematology, Leeds Teaching Hospitals Trust, Leeds, UK.
¹⁴ Department of Hematology and Cell Therapy, European Society for Blood and Marrow Transplantation, Paris Office, Hopital Saint-Antoine, Paris, France.
¹⁵ Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁶ Department of Hematology King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
¹⁷ Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapies Program, Mayo Clinic, Jacksonville, FL, USA.
¹⁸ Acute Leukemia Working Party, Paris Study Office, European Society for Blood and Marrow Transplantation, Paris, France.
¹⁹ Romagna Transplant Network, Ravenna, Italy.
²⁰ University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia.
²¹ Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
²² Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Roma, ItalyEurocord, Hôpital Saint Louis, Paris, France.
²³ Hematology Department, Hospital Universitari i Politecnic La Fe. Instituto de Investigación Sanitaria La Fe, Valencia, CIBERONC, Instituto Carlos III, Madrid, Spain.
²⁴ Department of Hematology and Oncology, Augsburg University Hospital, Augsburg, Germany.
²⁵ Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁶ BMT Unit, University of Patras, Patras, Greece.
²⁷ Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands.
²⁸ Department of Hematology, Institut Paoli-Calmettes, Marseille, France.
²⁹ Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
³⁰ Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Israel.

PMID: 32241850
PMCID: PMC7271578
DOI: 10.3324/haematol.2019.243410

Abstract

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.

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References

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[1] Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002;100(5):1532–1542. - PubMed

[2] Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002;100(5):1532–1542. - PubMed

[3] Griffith J, Black J, Faerman C, et al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell. 2004;13(2):169–178. - PubMed

[4] Griffith J, Black J, Faerman C, et al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell. 2004;13(2):169–178. - PubMed

[5] Mizuki M, Fenski R, Halfter H, et al. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood. 2000;96(12):3907–3914. - PubMed

[6] Mizuki M, Fenski R, Halfter H, et al. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood. 2000;96(12):3907–3914. - PubMed

[7] Hayakawa F, Towatari M, Kiyoi H, et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene. 2000;19(5): 624–631. - PubMed

[8] Hayakawa F, Towatari M, Kiyoi H, et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene. 2000;19(5): 624–631. - PubMed

[9] Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–344. - PMC - PubMed

[10] Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–344. - PMC - PubMed

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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

Affiliations

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

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