title: Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease.
abstract: Although allogeneic haematopoietic stem cell transplantation (HSCT) still represents the only consolidated possibility of cure for sickle cell disease (SCD) patients, its use has been limited by the risk of morbidity and mortality associated with conventional myeloablative therapy. The introduction of treosulfan to replace busulfan in conditioning regimens has recently been explored by virtue of its lower toxicity profile. We report our experience with a treosulfan/thiotepa/fludarabine conditioning for human leucocyte antigen (HLA)-matched sibling or unrelated donor-HSCT in 15 children with SCD, and compare patient outcomes with those of a historical cohort (15 patients) given a busulfan-based regimen. Engraftment was achieved in 28 out of 30 patients (93%), with one case of graft failure in either group. The conditioning regimen was well tolerated in both groups, with no cases of grade III-IV regimen-related toxicity. The 7-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 100% and 93%, respectively, with a 93% DFS in both busulfan and treosulfan groups. No SCD-related adverse events occurred after engraftment in patients with complete or mixed donor chimerism. This retrospective analysis suggests that a treosulfan-based conditioning regimen is able to ensure engraftment with excellent OS/DFS and low regimen-related toxicity in patients with SCD.
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Strocchio
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mina
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgiani
authors.affiliation: Unità Pediatria, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Giraldi
authors.affiliation: Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Vinti
authors.affiliation: Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.affiliation: Farmacocinetica Clinica dei Trapianti e delle Malattie Autoimmuni, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.affiliation: Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.|Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D008297:Male; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: C018404:treosulfan; D002066:Busulfan
keywords: conditioning regimen; haematopoietic stem cell transplantation; regimen-related toxicity; sickle cell disease; treosulfan