[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: We studied the outcome of 24 peripheral blood stem cell (PBSC) graft recipients, who were T-cell depleted (TCD) with either 20 mg (n = 14) or 10 mg (n = 10) Campath-1H in vitro, in comparison with a retrospective cohort of 23 unmanipulated (UM) PBSC recipients. While the neutrophil engraftment was similar, the platelet engraftment occurred earlier in the TCD group (d 11 vs 14). The incidence of acute and chronic graft-versus-host-disease (GVHD) was 8.7% and 4.4% in the TCD group, respectively, compared with 47.7% and 56.3% in UM group (P < 0.001). In the TCD group, 5/6 chronic myeloid leukaemia (CML) and 4/18 non-CML patients relapsed (vs 0/6 and 3/17 in UM group, P = 0.06). All four molecular or cytogenetic relapses of CML were disease-free survivors following donor lymphocyte infusion. There was no difference in the incidence of serious infection between the TCD and UM groups and the lymphocyte recovery at 100 d was comparable. In the TCD cohort, the lymphocyte recovery was quicker in the 10 mg Campath-1H group. The non-relapse mortality (19.1%vs 66.3%) and 3 year survival (73.1 vs 19.2) were improved in the TCD group (P = 0.05). Thus elimination of late mortalities related to chronic GVHD and a rapid immune reconstitution, limiting either infection or relapse related deaths, contributed to an improved outcome following T-cell depletion with Campath-1H "in the bag".
British Journal of Haematology 05/2003; 121(1):109-18. · 4.94 Impact Factor