Prophylactic infusion of CD4 positive donor lymphocytes early after T-cell depleted stem cell transplantation

Allogeneic hematopoietic stem-cell transplantation (allo-SCT) regimens using
the CD52 antibody alemtuzumab for T cell depletion demonstrate efficient
engraftment and reduced graft-versus-host disease (GVHD). However,
alemtuzumab-containing regimens result in decreased post-transplant
anti-infection immunity. Due to poor T cell immune reconstitution, particularly
of the CD4+ T-cell subset, T cell dependent anti-tumor effects are also
impaired, requiring the administration of donor lymphocyte infusions (DLI)
early after transplantation. Although unmanipulated DLI can induce considerable
anti-tumor responses and immune reconstitution, morbidity and mortality due to
GVHD occur frequently.
Several studies have shown the capacity of CD8 depleted DLI to improve immune
reconstitution. In a small randomized trial, infusion of CD8 depleted DLI six
months after T-cell depleted SCT was associated with considerable less severe
GVHD than infusion of unmanipulated DLI with no difference in relapse rates.
However, CD8 depletion appears not to be able to completely eliminate GVHD,
possibly due to residual low numbers of CD8+ cells. DLI based on selection of
CD4+ positive donor cells may be more effective in preventing GVHD and may
improve immune reconstitution.

In this phase II study, the toxicity and treatment effects of early donor
derived CD4+ lymphocyte infusion, three months after SCT, will be evaluated

Randomized open label single centre intervention study.

The intervention is the infusion of a subset of donor lymphocytes (the CD4+
cells), three months after stem cell transplantation.

Participating patients will visit the outpatient clinic once every two weeks
for physical examination and blood sampling, which is at this moment the
standard care for patients during the first six months after allogeneic stem
cell transplantation at our institution. The total amount of blood which will
be taken for study purposes will be maximally 250 cc in a three months period.
One extra bone marrow examination will be performed (six weeks after CD4+
infusion). Theoretically, the risk of CD4+ donor lymphocyte infusion is acute
GVHD, as is seen in patients receiving total donor lymphocyte infusion after
allogeneic stem cell transplantation.