Impact of alemtuzumab pharmacokinetics on T-cell dynamics, graft-versus-host disease and viral reactivation in patients receiving allogeneic stem cell transplantation with an alemtuzumab-based T-cell-depleted graft.
Transpl Immunol
; 57: 101209, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31207283
ABSTRACT
Administration of alemtuzumab (targeting the CD52 antigen) to the patient (in-vivo) or to the graft (in-vitro) before allogeneic stem cell transplantation (alloSCT) decreases the incidence of graft-versus-host disease (GvHD). Effectiveness of this treatment relies on depletion of donor T cells. Currently, no data are available on alemtuzumab pharmacokinetics and pharmacodynamics in patients who received combined in-vivo and in-vitro alemtuzumab-based T-cell depletion. In this prospective study, we analyzed alemtuzumab pharmacokinetics and its effect on the circulating T cells in 36 patients who received an allogeneic T-cell-depleted graft by addition of 20â¯mg alemtuzumab "to the bag" with or without prior alemtuzumab (30â¯mg cumulative dose intravenously) as part of the conditioning regimen. Effective T-cell depletion was shown for all patients, even though alemtuzumab plasma levels varied considerably. Peak alemtuzumab levels were observed directly after graft infusion and were not associated with the number of circulating T cells pre-infusion, but with plasma volumes of the patients. All patients engrafted, confirming feasibility of this transplantation protocol. Only three patients with low alemtuzumab levels developed acute GvHD (grade II in 2 patients and grade III in 1 patient). Persistence of circulating alemtuzumab at 3â¯weeks after transplantation had prevented reconstitution of CD52-positive T cells when alemtuzumab plasma levels were above 0.7⯵g/mL. However, overall T-cell reconstitution did not correlate with the levels of alemtuzumab exposure, due to early reconstitution of CD52-negative alemtuzumab-resistant T cells. The protective effect of these cells likely explains the low incidence of Epstein-Barr-virus- and cytomegalovirus-related disease despite circulating alemtuzumab.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Infecções por Citomegalovirus
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Herpesvirus Humano 4
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Transplante de Células-Tronco Hematopoéticas
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Infecções por Vírus Epstein-Barr
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Citomegalovirus
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Aloenxertos
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Alemtuzumab
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Doença Enxerto-Hospedeiro
Tipo de estudo:
Guideline
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Transpl Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
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TRANSPLANTE
Ano de publicação:
2019
Tipo de documento:
Article