title: T- and B-cell immune reconstitution and clinical outcome in patients with multiple myeloma receiving T-cell-depleted, reduced-intensity allogeneic stem cell transplantation with an alemtuzumab-containing conditioning regimen followed by escalated donor lymphocyte infusions.
abstract: Immune reconstitution after conventional allogeneic transplantation is a major determinant of survival. We conducted a detailed investigation of T- and B-cell immune reconstitution and clinical outcome in 19 patients with multiple myeloma undergoing reduced-intensity stem cell transplantation using in vivo T-cell depletion with alemtuzumab. These patients experienced delayed T-cell recovery, particularly in the naïve (CD45 RA+) CD4 compartment. T-cell receptor spectratype analysis showed a reduced repertoire diversity, which improved rapidly after the administration of donor leucocyte infusions and subsequent conversion to full donor T-cell chimaerism. Post-transplant recovery of CD19+ B cells was also delayed for up to 18 months. Spectratype analysis of IgH CDR3 repertoire revealed a gradual normalization in IgM spectratype complexity by 6-12 months after transplant. There was a high incidence of viral infection, particularly cytomegalovirus reactivation, but the regimen-related mortality was low, perhaps because of the very low incidence of acute graft-versus-host disease (GVHD; grade I-II skin GVHD was seen in 5/19 patients). Over 80% of all patients have relapsed at a median of 283 (range 153-895) d after transplant, suggesting that the initially low rate of GVHD comes at a high price with regard to the desired graft-versus-myeloma effect.
authors.affiliation: Department of Haematology, University College London Hospitals NHS Trust, UK. shirley.dsa@uclh.nhs.uk
authors.forename: Shirley
authors.initials: S
authors.lastname: D'Sa
authors.forename: Karl
authors.initials: K
authors.lastname: Peggs
authors.forename: Arnold
authors.initials: A
authors.lastname: Pizzey
authors.forename: Stephanie
authors.initials: S
authors.lastname: Verfuerth
authors.forename: Dharsha
authors.initials: D
authors.lastname: Thuraisundaram
authors.forename: Michael
authors.initials: M
authors.lastname: Watts
authors.forename: Harry
authors.initials: H
authors.lastname: White
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Anthony
authors.initials: A
authors.lastname: Goldstone
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
authors.forename: Kwee
authors.initials: K
authors.lastname: Yong
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D033581:Stem Cell Transplantation; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D016207:Cytokines; D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D000074323:Alemtuzumab