Reconstitution of the Epstein-Barr virus-specific cytotoxic T-lymphocyte response following T-cell-depleted myeloablative and nonmyeloablative allogeneic stem cell transplantation.
The recovery of circulating antigen-specific T-cell immunity to Epstein-Barr virus (EBV) was determined in ELIspot assays following allogeneic myeloablative or nonmyeloablative stem cell transplantation (MST/NST). In 8 of 12 MST patients receiving an alemtuzumab-treated graft, the frequency of the EBV-specific reactivities was similar to or greater than that seen in the healthy controls. A response was detectable in 3 of 6 and 6 of 9 patients by 3 and 6 months, respectively, and in all patients by one year following MST. In contrast, only 1 of 9 (95% confidence interval [CI], 0-2.8) patients made a detectable EBV-specific response by 6 months following NST conditioned with fludarabine, melphalan, and alemtuzumab. Responses were detected in 7 of 10 patients by 1 year after NST. Parallel surveillance demonstrated that other virus infections occurred more frequently and earlier after transplantation in NST patients. The use of alemtuzumab in vivo in the nonmyeloablative conditioning might have resulted in the delay in EBV-specific T-cell recovery and increased virus infections.
Chakrabarti
Suparno
S
Department of Haematology, Birmingham Heartlands Hospital, Birmingham, United Kingdom.
Milligan
Donald W
DW
Pillay
Deenan
D
Mackinnon
Stephen
S
Holder
Kathleen
K
Kaur
Narinder
N
McDonald
Dorothy
D
Fegan
Christopher D
CD
Waldmann
Herman
H
Hale
Geoff
G
Rickinson
Alan
A
Steven
Neil
N
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use; D000956:Antigens, Viral / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D020031:Epstein-Barr Virus Infections / Q000139:chemically induced / Q000209:etiology / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008212:Lymphocyte Depletion; D013601:T-Lymphocytes; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000956:Antigens, Viral; D000074323:Alemtuzumab