Publication Date:
2011-11-18
Description:
Abstract 3020FN2 Background: The intensive T-cell depletion of the graft accompanying haploidentical stem cell transplantation (SCT) delays immune reconstitution and results in frequent and rapidly lethal infectious complications. The ability to accelerate immune reconstitution following HLA-haploidentical-SCT would extend safe transplantation to the large number of patients who do not have an HLA-matched donor. Methods: Twenty-seven adults with very high-risk malignancy entered a Phase I clinical trial of haplo-identical T-cell depleted allogeneic SCT followed by an immunotherapeutic strategy consisting of alloreactive T-lymphocyte depleted cells to accelerate immune reconstitution (ATIR) while preventing graft-versus-host disease (GVHD). Selective elimination of host-reactive T cells was achieved using a dibromorhodamine-based photodepletion approach. All stem cell grafts underwent in vitro immunomagnetic T cell depletion using CD34+ positive cell selection (Miltenyi). The myeloablative regimen consisted of TBI (1200 cGy), thiotepa (5 mg/kg), ATG (12.5 mg/kg) and fludarabine (200 mg/m2). No GVHD prophylaxis was administered. Results: Eight patients were enrolled and subsequently removed from the study because of leukemia relapse (n=4) or late identification of an unrelated donor (n=4). All 8 patients died. Nineteen patients (11 M, 8 F) with very high-risk hematologic malignancies (mostly refractory or relapsed acute myeloid leukemia (10) and myelodysplastic syndromes (4), and refractory biphenotypic leukemia (1), CLL (2), CML (1) and NHL (1)) proceeded with the trial. Median age was 54 years (range: 20–62). Patient and disease characteristics were similar between patient cohorts. Patients received incremental doses of ATIR cells, from 1×104 to 5×106 CD3 cells/kg at a median of 30 days (range: 28–39) after SCT. Greater than 90% of activated (CD25+CD44+) CD4 and CD8 T cells (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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