No abstract

A critical factor limiting the availability of histocompatible platelet transfusions for alloimmunized, thrombocytopenic patients is the large pool of HLA-typed donors needed to procure platelets perfectly matched for HLA antigens. We have, therefore, investigated the effectiveness of platelets obtained from donors having lesser degrees of histocompatibility. In 421 transfusions administered to 59 alloimmunized patients who were refractory to "random donor" platelets, it was found that platelets mismatched for 1 or 2 "cross-reactive" HLA antigens were in most instances as effective in increasing circulating platelet levels as perfectly matched platelets. A significant number of patients also responded to platelets from donors selectively mismatched for non-cross-reactive HLA antigens. The latter group had a significantly reduced frequency of the antigen HLA-A2 (13%) in comparison to the total patient population (49%). Use of donors whose HLA antigens are serologically cross-reactive with those of alloimmunized patients provides approximately 10 times as many prospective donors as does selection based on matching for HLA and simplifies the procurement of hemostatically effective platelets for such patients.

No 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.

No abstract