TY - JOUR
T1 - Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation
T2 - A phase 1/2 study
AU - André-Schmutz, Isabelle
AU - Le Deist, Françoise
AU - Hacein-Bey-Abina, Salima
AU - Vitetta, Ellen
AU - Schindler, John
AU - Chedeville, Gaelle
AU - Vilmer, Etienne
AU - Fischer, Alain
AU - Cavazzana-Calvo, Marina
N1 - Funding Information:
The study was supported in part by Assistance Publique-Hopitaux de Paris; INSERM; Amgen, France; and a European grant S14PCT950029. I AndréSchmutz is supported by a fellowship from Association Française contre les Myopathies (THG).
PY - 2002/7/13
Y1 - 2002/7/13
N2 - 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.
AB - 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.
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U2 - 10.1016/S0140-6736(02)09413-8
DO - 10.1016/S0140-6736(02)09413-8
M3 - Article
C2 - 12126823
AN - SCOPUS:0037072113
SN - 0140-6736
VL - 360
SP - 130
EP - 137
JO - Lancet
JF - Lancet
IS - 9327
ER -