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Lancet. 2002 Jul 13;360(9327):130-7.

Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study.

Author information

1
Laboratoire de Thérapie Cellulaire et Génique, INSERM U 429, Hôpital Necker Enfants Malades, Paris, France.

Abstract

BACKGROUND:

Allogeneic haemopoietic stem-cell transplantation (HSCT) is the treatment of choice for many haematological malignancies and inherited disorders. When stem cells for transplantation come from a human leucocyte antigen matched unrelated donor, or from a partly mismatched related donor, ex-vivo T-cell depletion of the graft can prevent development of graft-versus-host disease, but lead in turn to a delay in immune reconstitution and a concordant increase in incidence of opportunistic infections and leukaemic relapses. We aimed to infuse T cells selectively depleted in allogeneic T cells that cause graft-versus-host disease using an ex-vivo procedure designed to eliminate alloactivated donor T cells, with an immunotoxin that reacts with a cell surface activation antigen, CD25.

METHODS:

We did a phase 1/2 study, in which 1-8 x 10(5) allodepleted T cells/kg were infused between days 15 and 47 into 15 paediatric patients who had acquired or congenital haemopoietic disorders and who received HSCT on day 0. Occurrence of graft-versus-host disease and time to immune reconstitution were assessed. No treatment for graft-versus-host disease was given.

FINDINGS:

Less than 1% residual anti-host alloreactivity was recorded in 12 of 16 procedures. Other immune responses were preserved by the allodepletion procedure in 12 cases. No cases of severe (greater than grade II) graft-versus-host disease arose. Evidence for early T-cell expansion was shown in three patients with continuing viral infections. Specific antiviral responses, such as strong cytolytic activity, were noted.

INTERPRETATION:

Our results show that ex-vivo selective depletion of T cells that cause graft-versus-host disease is efficient and feasible, even in haploidentical settings.

PMID:
12126823
DOI:
10.1016/S0140-6736(02)09413-8
[Indexed for MEDLINE]

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