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

• Published in: Biology of blood and marrow transplantation 2016-03, Vol.22 (3), p.456-461
• Main Authors: Patel, Khilna, Parmar, Sapna, Shah, Shreya, Shore, Tsiporah, Gergis, Usama, Mayer, Sebastian, van Besien, Koen
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adult; Aged; Alemtuzumab; Allografts; Antibodies, Monoclonal, Humanized - administration & dosage; Bone marrow transplantation; Female; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Infusion-related reactions; Injections, Subcutaneous; Intravenous alemtuzumab; Male; Melphalan - administration & dosage; Middle Aged; Subcutaneous alemtuzumab; Transplantation Conditioning; Unrelated Donors; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2015.10.022

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.