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

Anna Dodero, Matteo Carrabba, Raffaella Milani, Elena Rizzo, Anna Raganato, Vittorio Montefusco, Lucia Farina, Marco Milanesi, Paolo Longoni, Carmelo Carlo-Stella, Paolo Corradini

Research output: Contribution to journalArticlepeer-review

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+/μL and 500 CD8 +/μL were 6 and 9 months, respectively. Natural killer cells remained between the value of 300/μL and 500/μL throughout the period of follow-up whereas the median time to reach CD19+ blood concentrations of >200 cells/μL 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.

Original languageEnglish
Pages (from-to)920-927
Number of pages8
JournalExperimental Hematology
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 2005

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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