Transplantation of Haploidentical CD34+ Purified Peripheral Blood Stem Cells With NK-Cell Add-Back Following Conditioning With Total Body Irradiation, Thiotepa, Fludarabine and OKT3
- Determine the effect of haploidentical donor CD34+ purified peripheral blood stem cells
and donor natural killer (NK) cells on the risk of developing grades III-IV acute
graft-vs-host disease in patients with leukemia or other hematologic diseases.
- Determine the risk for mortality from infection before day 180 in patients treated with
- Determine the risk for graft rejection in patients treated with this regimen.
- Determine the risk for life-threatening infections in patients treated with this
- Determine the concentration of subsets of NK, NK-T, T cells, and dendritic cells in the
CD34+ NK/NK-T-enriched graft.
- Determine cytomegalovirus-specific T-cells in product and donor graft.
- Determine the genotype and phenotype of donor killer cell immunoglobulin-like receptor
expression according to time after hematopoietic stem cell transplantation (HSCT).
- Determine the reconstitution of NK function according to time after HSCT.
- Determine the expression of NKG2 ligands of leukemic blasts.
OUTLINE: Patients are stratified according to age (≤ 7 years vs > 7 years).
- Conditioning regimen: Patients 7 years of age or younger undergo total-body irradiation
(TBI) twice daily on days -11 to -9. Patients over 7 years of age undergo TBI once on
day -9. All patients receive thiotepa IV over 2 hours on days -8 and -7, fludarabine
phosphate IV on days -6 to -3 and muromonab-CD3 on days -6 to 6. Patients with acute
lymphoblastic leukemia or leukemia in the spinal fluid also receive methotrexate
intrathecally prior to and after donor peripheral blood stem cell (PBSC)
- Donor PBSC transplantation: Patients undergo donor PBSC transplantation comprising
CD34+ purified PBSCs and natural killer (NK) cells on day 0.
Blood samples are collected in weeks 1-4, 6, 8, and 12. Analysis of samples includes
quantitation of NK, NK-T, and T-cell subsets (CD3, CD4, and CD8) by flow cytometry; donor
killer cell immunoglobulin-like receptor genotype and phenotype; interferon-gamma levels;
and NK cytotoxicity. Samples are also analyzed by leukemic blast assay to determine if
ligands that activate NK cells are expressed.
After completion of study therapy, patients are followed periodically.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Risk of developing grades III-IV acute graft-vs-host disease (GVHD)
Ann Woolfrey, MD
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|
|Seattle Cancer Care Alliance||Seattle, Washington 98109|