title: Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma.
abstract: We compared antithymocyte globulin (ATG) with alemtuzumab in 73 patients with multiple myeloma, who underwent reduced conditioning with melphalan/fludarabine, followed by allogeneic stem cell transplantation from human leucocyte antigen-matched or -mismatched unrelated donors. The ATG group had more prior high-dose chemotherapies (P < 0.001), while bone marrow was used more as the stem cell source in the alemtuzumab group (P < 0.001). Alemtuzumab resulted in faster engraftment of leucocytes (P = 0.03) and platelets (P = 0.02) and in a lower incidence of acute graft versus host disease (GvHD) grades II-IV (24% vs. 47%, P = 0.06). More cytomegalovirus (CMV) seropositive patients in the alemtuzumab group experienced CMV reactivation (100% vs. 47%, P = 0.001). The cumulative incidence of treatment-related mortality at 2 years was 26% [95% confidence interval (CI) = 12-37%] for ATG vs. 28% (95% CI = 15-55%) for alemtuzumab, P = 0.7. There was no significant difference in the estimated 2-year overall and progression-free survival between ATG and alemtuzumab: 54% (95% CI: 39-75%) vs. 45% (95% CI: 28-73%) and 30% (95% CI: 16-55%) vs. 36% (95% CI: 20-62%) respectively. In multivariate analysis, treatment with alemtuzumab had a higher risk for relapse (hazard ratio: 2.37; P = 0.05) while killer immunoglobulin-like receptor (KIR)-ligand mismatch was protective for relapse (P < 0.0001). We conclude that alemtuzumab produced less acute GvHD, but higher probability of relapse. The data implicated a major role of KIR-ligand mismatched transplantation in multiple myeloma.
authors.affiliation: Bone Marrow Transplantation, University Hospital Hamburg, Hamburg, Germany. nkroeger@uke.uni-hamburg.de
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Bronwen
authors.initials: B
authors.lastname: Shaw
authors.forename: Simona
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.forename: Karl
authors.initials: K
authors.lastname: Peggs
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Thomas
authors.initials: T
authors.lastname: Binder
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiermann
authors.forename: Alejandro
authors.initials: A
authors.lastname: Madrigal
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehl
authors.forename: Herbert Gottfried
authors.initials: HG
authors.lastname: Sayer
authors.forename: Jörg
authors.initials: J
authors.lastname: Beyer
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.forename: Axel Rolf
authors.initials: AR
authors.lastname: Zander
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006086:Graft vs Host Disease; D006801:Humans; D016130:Immunophenotyping; D008558:Melphalan / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology* / Q000601:surgery; D016016:Proportional Hazards Models; D011971:Receptors, Immunologic / Q000032:analysis; D054340:Receptors, KIR; D012008:Recurrence; D012306:Risk; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan