title: Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.
abstract: Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Division of Immunology, Transplantation and Infectious Disease, Experimental Hematology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Cieri
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Greco
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Division of Regenerative Medicine, Stem Cells and Gene Therapy, Molecular and Functional Immunogenetics Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Crucitti
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Morelli
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giglio
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Levati
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Assanelli
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Matteo G
authors.initials: MG
authors.lastname: Carrabba
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Immunohematology and Transfusion Medicine Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bellio
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Immunohematology and Transfusion Medicine Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Milani
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lorentino
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Teresa Lupo
authors.initials: MT
authors.lastname: Stanghellini
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Tiago
authors.initials: T
authors.lastname: De Freitas
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Corti
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Division of Regenerative Medicine, Stem Cells and Gene Therapy, Molecular and Functional Immunogenetics Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.affiliation: Division of Immunology, Transplantation and Infectious Disease, Experimental Hematology Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonini
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Division of Regenerative Medicine, Stem Cells and Gene Therapy, Molecular and Functional Immunogenetics Unit, San Raffaele Scientific Institute, Milan, Italy. Electronic address: ciceri.fabio@hsr.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Division of Regenerative Medicine, Stem Cells and Gene Therapy, Hematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Peccatori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D020123:Sirolimus / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; C018404:treosulfan; D002066:Busulfan; D020123:Sirolimus
keywords: Allogeneic stem cell transplantation; Haploidentical transplantation; Peripheral blood stem cell transplantation; Post-transplantation cyclophosphamide; Sirolimus