Thymoglobuline in Non-myeloablative Allogeneic Stem-cell Transplantation
Status:
Completed
Trial end date:
2007-11-01
Target enrollment:
Participant gender:
Summary
Allogeneic stem cell transplantation is the treatment of choice for a growing number of
malignant and non-malignant indications. Until recently, myeloablative in conjunction with
immunosuppressive conditioning was considered mandatory for the elimination of malignant
hematopoietic cells and to prevent graft rejection. The aim of allogeneic non-myeloablative
stem cell transplantation (NST) is to induce host-to-graft tolerance with fast and durable
engraftment of donor stem cells, by means of conditioning, which is well-tolerated by
patients. The rationale behind the NST strategy is to induce optimal graft-versus-leukemia
(GVL) effects for the elimination of all malignant cells by alloreactive immunocompetent
cells from a matched donor as an alternative to standard high-dose myeloablative chemo
radiotherapy. The NST protocol is therefore mainly based on immunosuppression and thus
contains fludarabine, low dose busulfan and anti-T-lymphocyte globulin (ATG). Thymoglobuline
is a polyclonal rabbit antiserum specific for human T cells used in organ transplantation for
induction of tolerance and rejection prevention and treatment. It was also used in stem-cell
transplantation (SCT) for the same purposes (e.g. for generation of tolerance and rejection
preclusion) as well as a treatment for graft-versus-host disease (GVHD). Data from
myeloablative protocols suggest that ATG before SCT significantly reduces the risk for grade
III-IV acute GVHD. This does not translate to a reduction in transplant-related mortality
(TRM) because of the increased risk for infections and thus survival is unchanged. Extensive
chronic GVHD was also significantly shown to be reduced in patients receiving ATG in the
myeloablative setting. However, the role of ATG in the NST protocol was never evaluated in a
prospective randomized trial. In view of the preliminary data suggesting of an additive
effect of ATG in these circumstances we, the investigators at Hadassah Medical Organization,
evaluate the effect of ATG in NST by a prospective randomized trial.