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

Isabelle André-Schmutz, Françoise Le Deist, Salima Hacein-Bey-Abina, Ellen Vitetta, John Schindler, Gaelle Chedeville, Etienne Vilmer, Alain Fischer, Marina Cavazzana-Calvo

Research output: Contribution to journalArticle

185 Scopus citations

Abstract

Background: Allogeneic haemopoietic stem-cell transplantation (HSCT) is the treatment of choice for many haemological 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 1-8×105 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.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalLancet
Volume360
Issue number9327
DOIs
StatePublished - Jul 13 2002

ASJC Scopus subject areas

  • Medicine(all)

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    André-Schmutz, I., Le Deist, F., Hacein-Bey-Abina, S., Vitetta, E., Schindler, J., Chedeville, G., Vilmer, E., Fischer, A., & Cavazzana-Calvo, M. (2002). Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: A phase 1/2 study. Lancet, 360(9327), 130-137. https://doi.org/10.1016/S0140-6736(02)09413-8