D'Sa, S.P.; (2007) Immune reconstitution of B cell and T cell compartments following reduced intensity allogeneic stem cell transplantation for myeloma. Doctoral thesis , University of London.

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Abstract

Immune reconstitution following conventional allogeneic transplantation is a major determinant of survival. A detailed investigation of T and B cell immune reconstitution and clinical outcome in 19 patients with myeloma undergoing reduced intensity stem cell transplantation using in vivo T cell-depletion with alemtuzumab was undertaken. The rate of recovery of lymphocyte numbers and function following transplant was studied using immunophenotyping with 3-colour flow cytometry and intracellular cytokine staining. In addition, T and B cell spectratyping were used to study the repertoire of immune recovery. The patients in this study experienced delayed T cell recovery and T cell receptor spectratype analysis showed a reduced repertoire diversity, which improved rapidly following the administration of DLI and subsequent conversion to full donor T cell chimerism. Post transplant recovery of B cells was also significantly delayed. Spectratype analysis of IgH CDR3 repertoire revealed a gradual normalisation in spectratype complexity by 6- 12 months post transplant. There was a high incidence of viral infection, particularly CMV reactivation but the regimen related mortality was low, perhaps due to the very low incidence of severe acute graft-versus-host disease (GVHD). A total of 10 patients experienced GVHD. Of these patients, 8 eventually demonstrated a disease response alongside clinical evidence of GVHD, demonstrating that the graft-versus-myeloma effect is frequently obtained at the expense of GVHD. Over 80% of all patients have relapsed at a median of 9 months following transplant, suggesting that the initially low rate of GVHD has been achieved at the expense of the desired graft-versus-myeloma effect.

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