LYMPHOID RECONSTITUTION AFTER AUTOLOGOUS PBSC TRANSPLANTATION WITH FACS-SORTED CD34(+) HEMATOPOIETIC PROGENITORS

T-cell and B-cell reconstitution was studied in nine patients who rece ived 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 patien t 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 u sing flow cytometry and reverse transcriptase-polymerase chain reactio n (RT-PCR) amplification of VDJ T-cell receptor (TcR) sequences. Resto ration of normal numbers of peripheral blood T cells and B cells among recipients of FACS-sorted CD34(+) HPC was delayed compared to recipie nts of non-T-cell-depleted PBSC autografts, In both patient groups, th e circulating T cells were primarily CD4(-), CD8(+), alpha beta TcR+, and CD45RO(+), CD45RA(-) during the first 2 months after transplant. S ubsequent increases in the frequency of CD45RA(+) CD45RO(-) T cells oc curred at 2 to 3 months after transplant, suggesting maturation of CD3 4(+) hematopoietic progenitors to ''naive'' T cells. Analysis of the T cR repertoire after hematopoietic reconstitution demonstrated decrease d diversity of V beta TcR expression associated with global decreases in the absolute number of total peripheral blood T cells and most V be ta TcR+ subsets, Three of nine recipients of FACS-sorted CD34(+) HPC d emonstrated significant increases in the percentage of gamma delta(+) peripheral T cells and CD5(+) B cells at 3 to 9 weeks after transplant ation, and all patients had transient oligoclonal expansions of T cell s expressing specific V beta TcR. Transplantation with highly purified CD34(+) HPC results in reduced diversity of the peripheral T-cell rep ertoire during the early post-transplant period compared with patients receiving unmanipulated or MoAb-depleted transplants. (C) 1998 by The American Society of Hematology.