Objective. In vivo administration of alemtuzumab (an anti-CD52 antibody) is effective to decrease the incidence of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). However, posttransplant immune reconstitution is impaired, increasing the infection risk. We investigated the effect of in vivo administration of a low-dose alemtuzumab on GVHD prevention and kinetics of immune reconstitution. Patients and Methods. Twenty-seven patients entered a pilot study employing reduced-intensity conditioning and low-dose alemtuzumab (15 or 7.5 mg/m2) before peripheral blood allo-SCT from human leukocyte antigen-identical or one antigen-mismatched sibling donors. All lymphoid subsets were longitudinally studied at 1-3, 6, 9, 12 months after transplantation. T-cell receptor (TCR) spectratyping and T-cell receptor excision circles (TRECs) were also analyzed at various time points after allo-SCT. Results. All patients but one were engrafted. The probability of nonrelapse mortality at 100 days and 1 year were 7 and 11%, respectively; the overall survival at 2 years was 77%. The cumulative incidence of grade II-IV acute GVHD at day 100 was 11%. The overall incidence of chronic GVHD was 28%. The median time to achieve more than 200 CD4+/(mu)L and 500 CD8 +/(mu)L were 6 and 9 months, respectively. Natural killer cells remained between the value of 300/(mu)L and 500/(mu)L throughout the period of follow-up whereas the median time to reach CD19+ blood concentrations of >200 cells/(mu)L was 9 months. The normalization of TCR repertoire and increase of TREC counts began at 6 months after allo-SCT. Conclusion. We have shown that low-dose alemtuzumab is effective for GVHD prevention, but its use still impairs the immune reconstitution. (copyright) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.
Reduced-intensity conditioning containing low-dose alemtuzumab before allogeneic peripheral blood stem cell transplantation: graft-versus-host disease is decreased but T-cell reconstitution is delayed
C. Carlo-Stella;
2005-01-01
Abstract
Objective. In vivo administration of alemtuzumab (an anti-CD52 antibody) is effective to decrease the incidence of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). However, posttransplant immune reconstitution is impaired, increasing the infection risk. We investigated the effect of in vivo administration of a low-dose alemtuzumab on GVHD prevention and kinetics of immune reconstitution. Patients and Methods. Twenty-seven patients entered a pilot study employing reduced-intensity conditioning and low-dose alemtuzumab (15 or 7.5 mg/m2) before peripheral blood allo-SCT from human leukocyte antigen-identical or one antigen-mismatched sibling donors. All lymphoid subsets were longitudinally studied at 1-3, 6, 9, 12 months after transplantation. T-cell receptor (TCR) spectratyping and T-cell receptor excision circles (TRECs) were also analyzed at various time points after allo-SCT. Results. All patients but one were engrafted. The probability of nonrelapse mortality at 100 days and 1 year were 7 and 11%, respectively; the overall survival at 2 years was 77%. The cumulative incidence of grade II-IV acute GVHD at day 100 was 11%. The overall incidence of chronic GVHD was 28%. The median time to achieve more than 200 CD4+/(mu)L and 500 CD8 +/(mu)L were 6 and 9 months, respectively. Natural killer cells remained between the value of 300/(mu)L and 500/(mu)L throughout the period of follow-up whereas the median time to reach CD19+ blood concentrations of >200 cells/(mu)L was 9 months. The normalization of TCR repertoire and increase of TREC counts began at 6 months after allo-SCT. Conclusion. We have shown that low-dose alemtuzumab is effective for GVHD prevention, but its use still impairs the immune reconstitution. (copyright) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
