Poor lymphocyte recovery following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma

Positive selection of CD34⁺ cells in autologous grafts, designed to deplete tumour cells, also results in T-cell depletion. To assess the reconstitution of the different lymphocyte subsets and of the T-cell repertoire diversity following autologous transplantation of selected CD34⁺ peripheral blood stem cells (PBSC), we analysed sequential blood samples in eight patients autografted for advanced B-cell non-Hodgkin's lymphoma in a phase I–II pilot study. Although natural killer cell recovery was rapid, T- and B-cell recovery was delayed with a median of 110/μl CD4⁺, 175/μl CD8⁺ T cells and 45/μl B cells at 12 months post-transplant. The naive CD45RA⁺ T-cell compartment was profoundly deficient up to 12 months for both CD4⁺ and CD8⁺ subsets. A transient expansion of memory CD8⁺CD45RO⁺ T cells consisting of an increased percentage of CD57⁺CD28⁻ cells occurred within the first 3 months post-transplant, but the memory CD4⁺CD45RO⁺ T cells remained far below the normal value. The CD8⁺CD28⁺ T-cell subset did not recover. Using multiplex PCR analysis of the T-cell receptor γ locus, we found that the repertoire diversity improved at 12 months after being poor and oligoclonal during the first 3 months post-transplant. As shown by monoplex PCRγ analysis of every VJ combination, despite T-cell depletion of the graft, mature T cells were carried over with the selected CD34⁺ PBSC and contributed to the T-cell recovery after transplantation.