title: High rate of hematological responses to sorafenib in FLT3-ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation.
abstract: Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3-ITD-positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off-label use of the tyrosine kinase inhibitor sorafenib, either alone or in association with hypomethylating agents and adoptive immunotherapy, in 13 patients with post-transplantation FLT3-ITD-positive AML relapses. Hematological response was documented in 12 of 13 patients (92%), and five of 13 (38%) achieved complete bone marrow remission. Treatment was overall manageable in the outpatient setting, although all patients experienced significant adverse events, especially severe cytopenias (requiring a donor stem cell boost in five patients) and typical hand-foot syndrome. None of the patients developed graft-vs.-host disease following sorafenib alone, whereas this was frequently observed when this was given in association with donor T-cell infusions. Six patients are alive and in remission at the last follow-up, and four could be bridged to a second allogeneic HSCT, configuring a 65 ± 14% overall survival at 100 d from relapse. Taken together, our data suggest that sorafenib might represent a valid treatment option for patients with FLT3-ITD-positive post-transplantation relapses, manageable also in combination with other therapeutic strategies.
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Tiago
authors.initials: T
authors.lastname: De Freitas
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Piemontese
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Matteo G
authors.initials: MG
authors.lastname: Carrabba
authors.affiliation: Molecular Hematology Laboratory, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tresoldi
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Messina
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Lupo Stanghellini
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Assanelli
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Corti
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Peccatori
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Unit of Immunogenetics, Leukemia Genomics and Immunobiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.affiliation: Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D012189:Retrospective Studies; D000077157:Sorafenib; D020080:Tandem Repeat Sequences; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; D051941:fms-Like Tyrosine Kinase 3
keywords: FLT3-ITD; acute myeloid leukemia; bone marrow transplantation; hematopoietic stem cell transplantation; sorafenib