HLA-Matched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T Cell Add-Back for Hematological Malignancies
One of the most effective ways of preventing lethal graft-versus-host disease (GVHD) after
allogeneic bone marrow transplantation (BMT) for leukemia is to remove T-lymphocytes from
the transplanted marrow. The reduced early mortality from T cell depletion is however
offset by an increased risk of leukemic relapse and infection. We have shown that bone
marrow transplants for leukemia depleted of T cells by elutriation and followed by delayed
add-back of donor T cells reduces GVHD while preserving an immune response to the
hematologic malignancy (the so-called graft-versus-leukemia (GVL) or graft-versus-myeloma
effect). The study highlighted a possible benefit of large doses of marrow progenitor cells
on transplant outcome. GVHD was reduced but not prevented by T cell depletion of the
marrow. The first objective of our BMT studies is to prevent GVHD from the transplant while
conserving GVL reactivity. This is a prerequisite to our second objective of determining
the risk of GVHD and the benefit from GVL from add-back of donor lymphocytes. These studies
will provide the basis for a planned trial adding back donor lymphocytes selected in vitro
to confer immunity against infectious agents and residual leukemia without causing GVHD.
In this study we will evaluate the use of T cell depleted peripheral blood progenitor cells
(PBPC) (instead of bone marrow) to optimize the stem cell and lymphocyte dose. Donors will
be given G-CSF and their mobilized PBPC harvested by leukapheresis. To minimize acute GVHD,
the transplant will be T cell depleted, using a new technique developed in normal volunteers
which improves T cell depletion and reduces stem cell loss (protocol 96-H-0049). The study
has two phases: The first phase evaluates engraftment and GVHD following T cell depleted
PBPC transplants. Stopping rules will be used to make modifications to the protocol in the
event of graft failure. Cyclosporine will be withdrawn from the protocol if the incidence
of acute GVHD is low or absent. In the second phase patients will receive add-back of donor
lymphocytes on day 45 and day 100 post transplant to prevent relapse and confer donor-immune
function. The risk of acute GVHD following this procedure will be determined. It is
planned to treat up to 55 patients aged between 10 and 60 years. The end points of the
study are graft take; acute and chronic GVHD, leukemic relapse, transplant-related and all
causes of mortality, cytomegalovirus reactivation and leukemia-free survival. Patients will
be followed for 5 years.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the feasibility of using G-CSF mobilized donor blood to transplant a predetermined dose of stem cells and T lymphocytes to recipients with hematologic malignacies.
A. John Barrett, M.D.
Principal Investigator
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
970099
NCT00001623
March 1997
January 2008
Name | Location |
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National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |