RAPID IMMUNOLOGICAL RECONSTITUTION FOLLOWING TRANSPLANTATION WITH MOBILIZED PERIPHERAL-BLOOD STEM-CELLS AS COMPARED TO BONE-MARROW

A majority of patients with intermediate of high-grade non-Hodgkin's l ymphoma (NHL) who are treated with high-dose chemotherapy (HDT) and he matopoietic stem cell transplantation subsequently relapse. Until rece ntly, transplantation was associated with high morbidity and mortality and the focus was on improving the safety of this procedure. However, the use of growth factors and other supportive measures has successfu lly reduced treatment mortality to less than 5%. Therefore, new strate gies need to be developed to eliminate the growth of any occult tumor cells reinfused with the stem cell products and the tumor cells remain ing in the patient. One approach is to improve the immune function of the patients by a more rapid immune reconstitution and augmentation of effector cell function. We report studies comparing immune recovery f ollowing HDT and autologous peripheral stem cell transplantation (PSCT ) as compared to autologous bone marrow transplantation (ABMT). These studies examined patients with intermediate and high-grade non-Hodgkin 's lymphoma (NHL) who were treated with HDT and PSCT (n = 56) or ABMT (n = 60). The PSCT patients had a significantly faster recovery of cir culating monocytes (CD14(+) cells), natural killer ((NK) CD56(+)) cell s, T helper (CD4(+)) cells, TCR gamma/delta cells, and naive T lymphoc ytes (CD45RA(+)). Following ABMT there was a significantly more rapid increase in the frequency of T suppressor/effector (CD8(+)) cells, B ( CD19(+)) cells, CD34(+) cells, polymorphonuclear leukocytes (PMN) and memory T lymphocytes (CD45RO(+)). The CD4:CD8 and CD45RA:CD45RO ratios were consistently higher in the PSCT group as compared to ABMT sugges ting an improved ratio of T helper to T effector/suppressor cells and naive T cells. The differences in cellular phenotype translated into i mproved T cell function (PHA mitogenesis) and T cell help (pokeweed mi togenesis). In addition, there was an accelerated reconstitution of NK cell activity following PSCT as compared to ABMT. The more rapid reco nstitution of NK and T cells in patients rescued with PSCT as compared to ABMT may contribute to an improved clinical outcome. Further, pati ents receiving a PSCT may be more responsive to adjuvant immunotherapy following transplantation.