Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using a Positive Stem Cell Selection Technique for T Cell Depletion, Followed by Delayed T Cell Add-Back
Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on
transplant techniques designed to decrease graft versus host disease (GVHD), increase the
graft-versus-leukemia (GVL) effect and reduce the risk of post-transplant graft rejection.
We have found that by controlling the stem cell (CD34+ cell) and T lymphocyte (CD3+ cell)
dose severe GVHD can be reduced whilst beneficial GVL effects can be preserved by postponed
donor lymphocyte infusion (DLI). We found that T cell depleted transplants using the
Nexell/Baxter Isolex 300i system to obtain high CD34+ doses depleted of lymphocytes were
safe to administer and associated with less severe acute GVHD and promising response rates
and overall survival, when combined with a delayed T cell add-back (DLI). This protocol is
designed to evaluate safety and efficacy of an improved T cell depletion procedure using the
Miltenyi CliniMACs system (CD34 reagent system) with a delayed T cell add back in the
HLA-matched peripheral blood stem cell transplant setting.
The protocol will accrue up to 68 subjects ages 10-75 with a hematological malignancy, in
whom allogeneic stem cell transplantation from an HLA-matched sibling would be routinely
indicated. 68 sibling donors will also be recruited. Diagnostic categories will include
acute and chronic leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma and
Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine
and total body irradiation, followed by an infusion of a stem cell product prepared using
the Miltenyi CliniMacs system for CD34 selection, and a delayed T-cell add back as donor
lymphocyte infusion (DLI) at day 90. Older subjects will receive a lower dose of
irradiation to reduce the regimen intensity.
Primary endpoint will be overall survival at day +200. Non-relapse mortality at day +200
will be monitored for safety. Secondary endpoints will be standard transplant outcome
variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD
and relapse of disease.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Increased rate of survival at day +200. Non-relapse mortality at day +200 will be monitored for safety.
Minocher M Battiwalla, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
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