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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.

Type

Journal article

Journal

Br J Haematol

Publication Date

10/2003

Volume

123

Pages

309 - 322

Keywords

Adult, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antibodies, Neoplasm, B-Lymphocyte Subsets, Cytokines, Female, Follow-Up Studies, Graft vs Host Disease, Humans, Immunocompetence, Immunoglobulin Heavy Chains, Immunoglobulins, Immunophenotyping, Killer Cells, Natural, Lymphocyte Count, Lymphocyte Depletion, Lymphocyte Transfusion, Male, Middle Aged, Multiple Myeloma, Stem Cell Transplantation, T-Lymphocyte Subsets, Transplantation Chimera, Transplantation Conditioning, Treatment Outcome