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Optimization of individualized graft composition: CD3/CD19 depletion combined with CD34 selection for haploidentical transplantation
Author(s) -
Huenecke Sabine,
Bremm Melanie,
Cappel Claudia,
Esser Ruth,
Quaiser Andrea,
Bonig Halvard,
Jarisch Andrea,
Soerensen Jan,
Klingebiel Thomas,
Bader Peter,
Koehl Ulrike
Publication year - 2016
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/trf.13694
Subject(s) - cd19 , leukapheresis , cd34 , cd3 , transplantation , medicine , stem cell , chemistry , immunology , surgery , antigen , biology , microbiology and biotechnology , cd8
BACKGROUND Excessive T‐cell depletion (TCD) is a prerequisite for graft manufacturing in haploidentical stem cell (SC) transplantation by using either CD34 selection or direct TCD such as CD3/CD19 depletion. STUDY DESIGN AND METHODS To optimize graft composition we compared 1) direct or indirect TCD only, 2) a combination of CD3/CD19‐depleted with CD34‐selected grafts, or 3) TCD twice for depletion improvement based on our 10‐year experience with 320 separations in graft manufacturing and quality control. RESULTS SC recovery was significantly higher (85%, n = 187 vs. 73%, n = 115; p < 0.0001), but TCD was inferior (median log depletion, −3.6 vs. −5.2) for CD3/CD19 depletion compared to CD34 selection, respectively. For end products with less than −2.5 log TCD, a second depletion step led to a successful improvement in TCD. Thawing of grafts showed a high viability and recovery of SCs, but low NK‐cell yield. To optimize individualized graft engineering, a calculator was developed to estimate the results of the final graft based on the content of CD34+ and CD3+ cells in the leukapheresis product. CONCLUSION Finally, calculated splitting of the starting product followed by CD3/19 depletion together with CD34+ graft manipulation may enable the composition of optimized grafts with high CD34+‐cell and minimal T‐cell content.