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Rapid and effective CD3 T‐cell depletion with a magnetic cell sorting program to produce peripheral blood progenitor cell products for haploidentical transplantation in children and adults
Author(s) -
Dykes Josefina H.,
Toporski Jacek,
Juliusson Gunnar,
Békássy Albert N.,
Lenhoff Stig,
Lindmark Anders,
Scheding Stefan
Publication year - 2007
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2007.01438.x
Subject(s) - progenitor cell , cell sorting , cell , peripheral blood , transplantation , medicine , immunology , stem cell , flow cytometry , biology , microbiology and biotechnology , genetics
BACKGROUND: Effective T‐cell depletion is a prerequisite for haploidentical peripheral blood progenitor cell (PBPC) transplantation. This study was performed to investigate the performance of magnetic cell sorting–based direct large‐scale T‐cell depletion, which is an attractive alternative to standard PBPC enrichment procedures. STUDY DESIGN AND METHODS: PBPCs were harvested from 11 human leukocyte antigen (HLA)‐haploidentical donors. T cells labeled with anti‐CD3–coated beads were depleted with a commercially available magnetic separation unit (CliniMACS, Miltenyi Biotec) with either the Depletion 2.1 (D2.1, n = 11) or the novel Depletion 3.1 (D3.1, n = 12) program. If indicated, additional CD34+ selections were performed (n = 6). Eleven patients received T‐cell‐depleted grafts after reduced‐intensity conditioning. RESULTS: The median log T‐cell depletion was better with the D2.1 compared to the D3.1 (log 3.6 vs. log 2.3, p < 0.05) and was further improved by introducing an immunoglobulin G (IgG)‐blocking step (log 4.5 and log 3.4, respectively). The D3.1 was superior to the D2.1 (p < 0.05) in median recovery of CD34+ cells (90% vs. 78%) and in median recovery of CD3– cells (87% vs. 76%). The median processing times per 10 10 total cells were 0.90 hours (D2.1) and 0.35 hours (D3.1). The transplanted grafts (directly T‐cell–depleted products with or without positively selected CD34+ cells) contained a median of 10.5 × 10 6 per kg CD34+, 0.93 × 10 5 per kg CD3+, and 11.6 × 10 6 per kg CD56+. Rapid engraftment was achieved in 10 patients. The incidences of acute graft‐versus‐host disease were less than 10 percent (Grade I/II) and 0 percent (Grade III/IV). CONCLUSION: The novel D3.1 program with IgG blocking enables highly effective, time‐saving large‐scale T‐cell depletion. Combining direct depletion techniques with standard CD34+ selection enables the composition of grafts optimized to the specific requirements of the patients.