A phase II study to assess engraftment and engraftment kinetics after double cord blood transplantation with a reduced-intensity conditioning regimen in patients eligible for allogeneic stem cell transplantation lacking a matched unrelated donor.

Background:

Many adult patients with a high risk hematological disease can not proceed to allogeneic stem cell transplantation because they lack a matched unrelated stem cell donor. Cord blood is an important alternative stem cell source in children. In adult patients single cord blood transplantation is associated with a high rate of graft failure and a delayed hematopoietic recovery due to the small number of hematopoietic stem cells in a single cord blood unit. It has been shown that double cord blood transplantation is a safe and promising approach to overcome this problem. Sustained hematopoiesis is usually derived from a single donor after double umbilical cord blood transplantation. So far, the distinct contributing factors which lead to the predominance of the prevailing cord blood graft are not known.



Objective:

Evaluation of engraftment and disease-free survival following double cord blood transplantation after a reduced intensity conditioning regimen in adult patients. In addition to description of clinical parameters biological studies will be performed in order to evaluate whether parameters can be identified that predict which graft ultimately prevails.



Study design:

Prospective phase II study.



Study population:

Patients with high risk haematological disease qualifiying for allogeneic stem cell transplantation but lacking a matched unrelated donor.



End points:

The primary endpoint is the cumulative incidence of graft failure.

The secundary end points are: time to engraftment of different cell lines, incidence of graft vs host disease, incidence of infection, TRM, disease-free survival and overall survival.

N/A

Evaluation of engraftment will take place at 1, 2, 3, 6, 12, and 24 months after transplantation.

Patients eligible for allogeneic stem cell transplantation lacking a matched unrelated donor are transplanted with a double cord blood graft. Transplantation will be preceded by a reduced-intensity conditioning regimen, consisting of cyclophosphamide 60 mg/kg, fludarabine 4x40 mg/kg and TBI 2x2 Gy. Prophylaxis for graft-versus-host disease consists of cyclosporine-A and mycophenolate mofetil.

After transplantation blood and bone marrow samples will be drawn to study the mechanism of engraftment.