title: Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant.
abstract: Severe graft-versus-host disease is a major barrier for non-T-cell-depleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs. the anti-thymocyte globulin-based) in adults with acute myeloid leukemia reported to the European Society for Blood and Bone Marrow Transplantation. A total of 308 patients were analyzed; 193 received post-transplant cyclophosphamide-based regimen and 115 anti-thymocyte globulin-based regimen as anti-graft-versus-host disease prophylaxis. The post-transplant cyclophosphamide-based regimen was more likely to be associated to bone marrow as graft source (60% vs. 40%; P=0.01). Patients in the post-transplant cyclophosphamide-based regimen group had significantly less grade 3-4 acute graft-versus-host disease than those in the anti-thymocyte globulin-based group (5% vs. 12%, respectively; P=0.01), comparable to chronic graft-versus-host disease. Multivariate analysis showed that non-relapse mortality was lower in the post-transplant cyclophosphamide-based regimen group [22% vs. 30%, Hazard ratio (HR) 1.77(95%CI: 1.09-2.86); P=0.02] with no difference in relapse incidence. Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45 (95%CI: 1.04-2.02); P=0.03] and leukemia-free survival [HR 1.48 (95%CI: 1.03-2.12); P=0.03] than those in the anti-thymocyte globulin-based group. In the multivariate analysis, there was also a trend for a higher overall survival [HR 1.43 (95%CI: 0.98-2.09); P=0.06] for post-transplant cyclophosphamide-based regimen versus the anti-thymocyte globulin-based group. Notably, center experience was also associated with non-relapse mortality and graft-versus-host disease-free, relapse-free survival. Haplo-SCT using a post-transplant cyclophosphamide-based regimen can achieve better leukemia-free survival and graft-versus-host disease-free, relapse-free survival, lower incidence of graft-versus-host disease and non-relapse mortality as compared to anti-thymocyte globulin-based graft-versus-host disease prophylaxis in patients with acute myeloid leukemia.
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France annalisa.ruggeri@aphp.fr.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ruggeri
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.|INSERM, UMRs 938, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Ospedale San Martino, Department of Haematology II, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.affiliation: Ospedale San Raffaele, Haematology and BMT, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lorentino
authors.affiliation: Tor Vergata University, Stem Cell Transplant Unit, Policlinico Universitario Tor Vergata, Rome, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Arcese
authors.affiliation: Ospedale Civile Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Pescara, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Santarone
authors.affiliation: Anadolu Medical Center Hospital, Bone Marrow Transplantation Department, Kocaeli, Turkey.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Gülbas
authors.affiliation: Programme de Transplantation & Therapie Cellulaire, Institut Paoli Calmettes, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Centro Unico Regionale Trapianti, Alberto Neri, Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Messina
authors.affiliation: Shariati Hospital, Hematology-Oncology and BMT Research, Teheran, Iran.
authors.forename: Ardeshi
authors.initials: A
authors.lastname: Ghavamzadeh
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Malard
authors.affiliation: A.O.U Citta della Salute e della Scienza di Torino, Presidio Molinette, Torino, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Bruno
authors.affiliation: Instituto de Investigacion Sanitaria Gregorio Marañon, Division of Hematology, Hospital Gregorio Marañon, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Diez-Martin
authors.affiliation: Medical Park Hospitals, Stem Cell Transplant Unit, Antalya, Turkey.
authors.forename: Yener
authors.initials: Y
authors.lastname: Koc
authors.affiliation: Ospedale San Raffaele, Haematology and BMT, Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France.|INSERM, UMRs 938, Paris, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Université Pierre et Marie Curie, Paris, France.|Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Tel Aviv University (TAU), Israel.|EBMT Paris Office, Hospital Saint Antoine, Paris, France.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D018890:Chemoprevention; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D012008:Recurrence; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide