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.
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.


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.


CONCLUSIONS
We have shown that low-dose alemtuzumab is effective for GVHD prevention, but its use still impairs the immune reconstitution.
Dodero
Anna
A
Division of Hematology, Istituto Nazionale Tumori and University of Milan, Milan, Italy. anna.dodero@istitutotumori.mi.it
Carrabba
Matteo
M
Milani
Raffaella
R
Rizzo
Elena
E
Raganato
Anna
A
Montefusco
Vittorio
V
Farina
Lucia
L
Milanesi
Marco
M
Longoni
Paolo
P
Carlo-Stella
Carmelo
C
Corradini
Paolo
P
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016516:CD4-CD8 Ratio; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D010865:Pilot Projects; D020127:Recovery of Function / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab