title: Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.
abstract: OBJECTIVE
  Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed.
  
  
  METHODS
  We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαβ and CD19 positive cells.
  
  
  RESULTS
  All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients.
  
  
  CONCLUSIONS
  Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Marzollo
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Calore
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Tumino
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Pillon
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Gazzola
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Destro
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Colombatti
authors.affiliation: Department of Transfusion Medicine, Azienda Ospedaliera Padova.
authors.forename: Piero
authors.initials: P
authors.lastname: Marson
authors.affiliation: Department of Transfusion Medicine, Azienda Ospedaliera Padova.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Tison
authors.affiliation: Department of Transfusion Medicine, Azienda Ospedaliera Padova.
authors.forename: Anna
authors.initials: A
authors.lastname: Colpo
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mainardi
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Gabelli
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Boaro
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Rossin
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Strano
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Quaglia
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Menzato
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sainati
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, University of Padova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
keywords: Haploidentical; Hematopoietic stem cell transplantation; Sickle cell disease; T-cell depletion; Treosulfan