Lymphoid Reconstitution After Autologous PBSC Transplantation With FACS-Sorted CD34+ Hematopoietic Progenitors

Abstract

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.

Influence of ex vivo purging with CliniMACS CD34+ selection on outcome after autologous stem cell transplantation in non‐Hodgkin lymphoma

“…In our study we showed that CD34 + selection as a purging method did not compromise the time needed for ANC recovery compared with the unpurged group. This finding correlates with the results in previous studies documenting similar neutrophil recovery between unmanipulated and CD34 + -selected autologous grafts (Bomberger et al, 1998;Vescio et al, 1999). However, it is noteworthy that most patients who developed CMV DNAemia in the immediate post-transplantation period had received a graft with CD34 + cell selection, indicating delayed T-cell reconstitution compared with that in non-manipulated grafting.…”

Long-term results of CD34+ cell transplantation in children with neuroblastoma

“…Depletion of substantial numbers of T cells from the grafts and a persistent decrease in CD4 + lymphocytes following CD34 + cell transplants may have predisposed these patients to viral infections. Highly purified CD34 + grafts may also result in a posttransplant reduction of the diversity of the peripheral T-cell repertoire compared to unmanipulated graft [26].…”

Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation

“…[1][2][3][4][5][6][7][8][9][10] Associated risks of high-intensity regimens, however, preclude broader use of this approach in spite of its capacity to dramatically diminish new focal inflammatory disease activity in the central nervous system (CNS) of MS patients, who are otherwise treatment refractory. [11][12][13][14][15] Hence, elucidating the immune mechanisms underlying the therapeutic effect of high-intensity HSCT could guide development of more selective treatments with a more favorable risk/benefit profile.…”