title: Treosulfan based reduced toxicity conditioning followed by allogeneic stem cell transplantation in patients with myelofibrosis.
abstract: Allogeneic transplantation is the only potentially curative strategy for myelofibrosis, even in the era of new drugs that so far only mitigate symptoms. The choice to proceed to allogeneic transplantation is based on several variables including age, disease phase, degree of splenomegaly, donor availability, comorbidities and iron overload. These factors, along with conditioning regimen and time to transplantation, may influence the outcome of ASCT. We report 14 patients affected by myelofibrosis with a median age of 57 years (range, 41-76) receiving a treosulfan-fludarabine based reduced toxicity conditioning. Patients (pts) received a stem cell transplantation from an HLA identical (n = 10) or matched unrelated donor (n = 4). All pts had a complete myeloablation followed by engraftment and in 12 out of 13 evaluated pts donor chimerism was 100% at 1 month. In most cases a reduction of splenomegaly and a reduction (or resolution) of bone marrow fibrosis was observed. After a median follow-up of 39 months (range, 3-106), the 3-year probability of overall survival and disease free survival was 54 +/- 14% and 46 +/- 14%, respectively. The cumulative incidence of non-relapse mortality at 2 years was 39 +/- 15%. Causes of non-relapse mortality were: infection (n = 2), GvHD (n = 2) and haemorrhage (n = 1). We can conclude that a treosulfan and fludarabine based conditioning has a potent myeloablative and anti-disease activity although non-relapse mortality remains high in this challenging clinical setting. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Claudiani
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Piemontese
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Assanelli
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Lupo-Stanghellini
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Carrabba
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Guggiari
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giglio
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Tiago
authors.initials: T
authors.lastname: De Freitas
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Magda
authors.initials: M
authors.lastname: Marcatti
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Corti
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Peccatori
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunghi
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
mesh_terms: D000368:Aged; D064591:Allografts; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000401:mortality* / Q000628:therapy*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D061349:Unrelated Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: bone marrow transplantation; hematopoietic stem cell transplantation; myeloproliferative disease; primary myelofibrosis; reduced-toxicity conditioning; treosulfan