Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors

被引:154
作者
Bomberger, C [1 ]
Singh-Jairam, M [1 ]
Rodey, G [1 ]
Guerriero, A [1 ]
Yeager, AM [1 ]
Fleming, WH [1 ]
Holland, HK [1 ]
Waller, EK [1 ]
机构
[1] Emory Univ, Sch Med, Div Hematol & Oncol, Dept Pathol,Stem Cell Biol Program, Atlanta, GA 30322 USA
关键词
D O I
10.1182/blood.V91.7.2588.2588_2588_2600
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 x 10(6) 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(+), alpha beta 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 V beta TcR expression associated with global decreases in the absolute number of total peripheral blood T cells and most V beta TcR+ subsets, Three of nine recipients of FACS-sorted CD34(+) HPC demonstrated significant increases in the percentage of gamma delta(+) 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 V beta 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. (C) 1998 by The American Society of Hematology.
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页码:2588 / 2600
页数:13
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