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+/microL and 500 CD8+/microL were 6 and 9 months, respectively. Natural killer cells remained between the value of 300/microL and 500/microL throughout the period of follow-up whereas the median time to reach CD19+ blood concentrations of >200 cells/microL 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.
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+/microL and 500 CD8+/microL were 6 and 9 months, respectively. Natural killer cells remained between the value of 300/microL and 500/microL throughout the period of follow-up whereas the median time to reach CD19+ blood concentrations of >200 cells/microL 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.
Authors: Rebecca A Marsh; Mi-Ok Kim; Chunyan Liu; Denise Bellman; Laura Hart; Michael Grimley; Ashish Kumar; Sonata Jodele; Kasiani C Myers; Sharat Chandra; Tom Leemhuis; Parinda A Mehta; Jack J Bleesing; Stella M Davies; Michael B Jordan; Alexandra H Filipovich Journal: Biol Blood Marrow Transplant Date: 2013-09-10 Impact factor: 5.742
Authors: A Spyridonidis; M Liga; E Triantafyllou; M Themeli; M Marangos; M Karakantza; N Zoumbos Journal: Bone Marrow Transplant Date: 2010-12-20 Impact factor: 5.483
Authors: Jonathan P Lane; Philippa T G Evans; Zohreh Nademi; Dawn Barge; Anthony Jackson; Sophie Hambleton; Terry J Flood; Andrew J Cant; Mario Abinun; Mary A Slatter; Andrew R Gennery Journal: Biol Blood Marrow Transplant Date: 2013-11-10 Impact factor: 5.742