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.
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.
D'Sa
Shirley
S
Department of Haematology, University College London Hospitals NHS Trust, UK. shirley.dsa@uclh.nhs.uk
Peggs
Karl
K
Pizzey
Arnold
A
Verfuerth
Stephanie
S
Thuraisundaram
Dharsha
D
Watts
Michael
M
White
Harry
H
Hale
Geoff
G
Waldmann
Herman
H
Goldstone
Anthony
A
Mackinnon
Stephen
S
Yong
Kwee
K
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D016207:Cytokines; D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D000074323:Alemtuzumab