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Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors.
Open accessAbstract
T-cell and B-cell reconstitution was studied in nine patients who received fluorescence activated cell sorter (FACS)-sorted autologous CD34+ hematopoietic progenitor cells (HPC). The mean numbers of T cells (CD3+), B cells (CD19+) and CD34+ HPC administered to each patient were .004, .002, and 1.8 × 106 cells/kg, respectively. After high-dose myeloablative chemotherapy (busulfan, cyclophosphamide, etoposide) CD34+ HPC were infused and lymphoid reconstitution was monitored using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of VDJ T-cell receptor (TcR) sequences. Restoration of normal numbers of peripheral blood T cells and B cells among recipients of FACS-sorted CD34+ HPC was delayed compared to recipients of non-T-cell–depleted PBSC autografts. In both patient groups, the circulating T cells were primarily CD4−, CD8+, αβ TcR+, and CD45RO+, CD45RA− during the first 2 months after transplant. Subsequent increases in the frequency of CD45RA+ CD45RO− T cells occurred at 2 to 3 months after transplant, suggesting maturation of CD34+hematopoietic progenitors to “naive” T cells. Analysis of the TcR repertoire after hematopoietic reconstitution demonstrated decreased diversity of Vβ TcR expression associated with global decreases in the absolute number of total peripheral blood T cells and most Vβ TcR+ subsets. Three of nine recipients of FACS-sorted CD34+ HPC demonstrated significant increases in the percentage of γδ+ peripheral T cells and CD5+ B cells at 3 to 9 weeks after transplantation, and all patients had transient oligoclonal expansions of T cells expressing specific Vβ TcR. Transplantation with highly purified CD34+ HPC results in reduced diversity of the peripheral T-cell repertoire during the early post-transplant period compared with patients receiving unmanipulated or MoAb-depleted transplants.
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“As a product that is enriched with CD34+ cells, CTX001 may have contributed to the delay in lymphocyte recovery, similar to what has been observed after T-cell-depleted transplantation.33,34”
From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [33]
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Metadata
- Authors
- Bomberger, C., Singh-Jairam, M., Rodey, G., Guerriero, A., Yeager, A. M., Fleming, W. H., Holland, H. K., & Waller, E. K.
- Affiliations
- Emory University (US)
- From the Stem Cell Biology Program, Emory University, Department of Pathology, Emory University, Division of Hematology and Oncology, Atlanta, GA.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1998-04-01
- Volume
- 91
- Issue
- 7
- Pages
- 2588-2600
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2407278011
- Cited by
- 183
- References
- 36
- Citations by year
- 2026: 1 · 2024: 5 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 7 · 2012: 10
- FWCI
- 12.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- lymphoid reconstitution, autologous stem cell transplantation, CD34+ hematopoietic progenitor cells, T cell reconstitution, B cell reconstitution, T cell receptor repertoire, naive T cells, γδ T cells, CD5+ B cells, oligoclonal expansion, myeloablative chemotherapy, T cell depletion
- MeSH terms
- Adult, B-Lymphocytes, Cell Differentiation, Cell Separation, Flow Cytometry, Graft Survival, Humans, Lymphoma, Non-Hodgkin, Middle Aged, T-Lymphocytes, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Antigens, CD34
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