title: Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.
abstract: Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571.
authors.affiliation: Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy. Electronic address: fabrizio.carnevale@ircc.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carnevale-Schianca
authors.affiliation: Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Caravelli
authors.affiliation: Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy; Department of Oncology, University of Torino, Turin, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Gallo
authors.affiliation: Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Coha
authors.affiliation: Department of Oncology, University of Torino, Turin, Italy; Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: D'Ambrosio
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation, and Cellular Therapy Division, Turin Metropolitan Transplant Center, A.O.U. Citta' della Salute e della Scienza di Torino, Ospedale Infantile Regina Margherita, Torino, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Vassallo
authors.affiliation: Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fizzotti
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation, and Cellular Therapy Division, Turin Metropolitan Transplant Center, A.O.U. Citta' della Salute e della Scienza di Torino, Ospedale Infantile Regina Margherita, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nesi
authors.affiliation: Regulatory Affairs, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Gioeni
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation, and Cellular Therapy Division, Turin Metropolitan Transplant Center, A.O.U. Citta' della Salute e della Scienza di Torino, Ospedale Infantile Regina Margherita, Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Berger
authors.affiliation: Collection and Processing Laboratory, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Polo
authors.affiliation: Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Loretta
authors.initials: L
authors.lastname: Gammaitoni
authors.affiliation: Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy; Department of Oncology, University of Torino, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Becco
authors.affiliation: Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Giraudo
authors.affiliation: Collection and Processing Laboratory, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Mangioni
authors.affiliation: Department of Oncology, University of Torino, Turin, Italy; Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Sangiolo
authors.affiliation: Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grignani
authors.affiliation: Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Rota-Scalabrini
authors.affiliation: Collection and Processing Laboratory, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Sottile
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation, and Cellular Therapy Division, Turin Metropolitan Transplant Center, A.O.U. Citta' della Salute e della Scienza di Torino, Ospedale Infantile Regina Margherita, Torino, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.affiliation: Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy; Department of Oncology, University of Torino, Turin, Italy; Department of Medical Oncology, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006648:Histocompatibility; D006801:Humans; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Allogeneic bone marrow transplantation; Graft-versus-host disease; Post-transplant cyclophosphamide