Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases

Trial Information

Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases

OBJECTIVES:

- Determine the efficacy and toxicity of stem cell-enriched, T-cell-depleted,
haplocompatible allogeneic hematopoietic stem cell transplantation in children with
high-risk myelodysplastic syndromes, high-risk leukemia, severe acquired or congenital
cytopenias, or primary immunodeficiency diseases.

- Determine the toxicity of a fludarabine and thiotepa-containing regimen in combination
with lower doses of antithymocyte globulin in these patients.

- Determine the engraftment rate in patients treated with this regimen.

- Define T-cell reconstitution in these patients.

- Determine the toxicity and effects of administering stem cell and T-cell boosts after
transplantation on hematopoiesis and immune reconstitution in these patients.

OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin
(ATG).

- Cytoreductive regimen: Patients undergo total body irradiation twice daily on days -9
to -7. Patients also receive fludarabine IV on days -6 to -2, thiotepa IV every 12
hours on day -6, and ATG IV on days -5 to -2.

- Transplantation: Patients undergo CD34-enriched, T-cell-depleted, haplocompatible
allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.

- Donor T-cell infusion:Patients with no active graft-vs-host disease and evidence of
engraftment but low absolute CD34+ lymphocyte count at 12 weeks post transplant may
receive donor CD3+ cells at 4-week intervals.

- Donor stem cell boost: Patients with engraftment but either cytokine or transfusion
dependent at 12 weeks post transplant may receive a boost of donor CD34+ cells.

Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the
optimum is determined. The optimum dose is defined as the dose at which both engraftment and
T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.

After the completion of study treatment, patients are followed periodically for 5 years and
then every 5 years thereafter.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.