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.
|Titolo:||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|
|Autori interni:||CARLO STELLA, CARMELO (Penultimo)|
CORRADINI, PAOLO (Ultimo)
CARRABBA, MATTEO GIOVANNI (Secondo)
|Parole Chiave:||T lymphocyte; adult; allogeneic peripheral blood stem cell transplantation; article; clinical article; concentration (parameters); dose response; female; follow up; graft versus host reaction; human; incidence; kinetics; lymphoid cell; male; mortality; natural killer cell; pilot study; priority journal; probability; survival; CD19 antigen; T lymphocyte receptor; alemtuzumab; cyclophosphamide; fludarabine; leukocyte antigen; thiotepa|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
Settore MED/06 - Oncologia Medica
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||10.1016/j.exphem.2005.05.009|
|Appare nelle tipologie:||01 - Articolo su periodico|
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