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.
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.
Authors: Scott R Solomon; Stephan Mielke; Bipin N Savani; Aldemar Montero; Laura Wisch; Richard Childs; Nancy Hensel; John Schindler; Victor Ghetie; Susan F Leitman; Thao Mai; Charles S Carter; Roger Kurlander; Elizabeth J Read; Ellen S Vitetta; A John Barrett Journal: Blood Date: 2005-04-07 Impact factor: 22.113
Authors: Stephan Mielke; Katayoun Rezvani; Bipin N Savani; Raquel Nunes; Agnes S M Yong; John Schindler; Roger Kurlander; Victor Ghetie; Elizabeth J Read; Scott R Solomon; Ellen S Vitetta; A John Barrett Journal: Blood Date: 2007-05-03 Impact factor: 22.113
Authors: J Michalek; R H Collins; H P Durrani; P Vaclavkova; L E Ruff; D C Douek; E S Vitetta Journal: Proc Natl Acad Sci U S A Date: 2003-01-16 Impact factor: 11.205