title: Comparison of Subcutaneous versus Intravenous Alemtuzumab for Graft-versus-Host Disease Prophylaxis with Fludarabine/Melphalan-Based Conditioning in Matched Unrelated Donor Allogeneic Stem Cell Transplantation.
abstract: The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days -7 to -3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting. Incidences of acute and chronic GVHD were similar between both arms. There was also no difference in reactivation of CMV/EBV viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, relapse, or survival.
authors.affiliation: Department of Pharmacy, New York-Presbyterian Hospital, New York, New York. Electronic address: khp9004@nyp.org.
authors.forename: Khilna
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Pharmacy, New York-Presbyterian Hospital, New York, New York.
authors.forename: Sapna
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Department of Pharmacy, New York-Presbyterian Hospital, New York, New York.
authors.forename: Shreya
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Medicine, New York-Presbyterian Hospital, New York, New York.
authors.forename: Tsiporah
authors.initials: T
authors.lastname: Shore
authors.affiliation: Department of Medicine, New York-Presbyterian Hospital, New York, New York.
authors.forename: Usama
authors.initials: U
authors.lastname: Gergis
authors.affiliation: Department of Medicine, New York-Presbyterian Hospital, New York, New York.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mayer
authors.affiliation: Department of Medicine, New York-Presbyterian Hospital, New York, New York.
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D064591:Allografts; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D019172:Transplantation Conditioning; D061349:Unrelated Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan
keywords: Bone marrow transplantation; Infusion-related reactions; Intravenous alemtuzumab; Subcutaneous alemtuzumab