Summary:ABMT may contribute to an improved clinical outcome. Further, patients receiving a PSCT may be more A majority of patients with intermediate or high-grade responsive to adjuvant immunotherapy following transnon-Hodgkin's lymphoma (NHL) who are treated with plantation. high-dose chemotherapy (HDT) and hematopoietic stem Keywords: PSCT; BMT; immunity; T cell; NHL; NK cell transplantation subsequently relapse. Until recently, cell F 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 successfully reduced High-dose chemotherapy (HDT) supported by hematopotreatment mortality to less than 5%. Therefore, new ietic stem cell transplantation and growth factor adminisstrategies need to be developed to eliminate the growth tration is increasingly used for patients with cancer. 1-3 Leuof any occult tumor cells reinfused with the stem cell kocyte and platelet recovery is more rapid following products and the tumor cells remaining in the patient.peripheral blood stem cell transplantation (PSCT) as comOne approach is to improve the immune function of the pared to bone marrow autografts (ABMT), if the peripheral patients by a more rapid immune reconstitution and stem cells (PSC) are collected after mobilization with hemaugmentation of effector cell function. We report studatopoietic growth factors, chemotherapy, or both. [4][5][6][7][8] In ies comparing immune recovery following HDT and addition, one retrospective study suggested an increase in autologous peripheral stem cell transplantation (PSCT) the progression-free interval following PSCT with steady as compared to autologous bone marrow transplanstate PSC as compared to ABMT, 9 although this obsertation (ABMT). These studies examined patients with vation requires confirmation as well as demonstration in a intermediate and high-grade non-Hodgkin's lymphoma prospectively randomized trial. 4,10,11 (NHL) who were treated with HDT and PSCT (n = 56) PSCT 6,12 may result in an earlier reconstitution of or ABMT (n = 60). The PSCT patients had a signifiimmune function following HDT as compared to cantly faster recovery of circulating monocytes (CD14 + ABMT 13,14 perhaps due to the lymphocytes that are trans- cells), natural killer ((NK) CD56 + ) cells, T helper (CD4 + )fused in the PSC product. To date, there have been limited cells, TCR␥/␦ cells, and naive T lymphocytes and conflicting studies on immune reconstitution following (CD45RA + ). Following ABMT there was a significantly PSCT and ABMT in humans. [15][16][17][18] Overall, there appears to more rapid increase in the frequency of T be wide phenotypic variability of cells in the suppressor/effector (CD8 + ) cells, B (CD19 + ) cells, CD34 + apheresis/transplant products themselves. 14 A significant cells, polymorphonuclear leukocytes (PMN) and memincrease in the frequency of CD8 + cells in the peripheral ory T lymphocytes (CD45RO + ). The CD4:CD8 and blood (PB) following both f...
The expansion of T and natural killer (NK) cells in growth factormobilized peripheral blood stem cell (PSC) products with interleukin-2 (IL-2) requires a reduction in monocyte frequency. Monocytes are enriched with stem cells during apheresis and, in this series of growth factor-mobilized PSC products from breast cancer patients, represented 36 f 6% of the cells in the product. Immunophenotyping studies revealed that monocytes inhibited the proliferation of NK cells (CD56' and CD3-CD8' CD56' cells) and T cells (CD3', CD4' , and CD8' cells) during IL-2 co-culture for 7, 14, or 21 days. A reduction in monocytes resulted in 61-fold expansion of CD3-CD8' CD56' cells compared with a 3.7-fold increase of CD3' cells by day 21. In addition, following IL-2 co-culture, cells from PSC products with a reduced frequency of monocytes had a significantly increased T cell mitogenic response and NK cell activity in PSC products compared with intact products. We suggest that monocytes inhibit the IL-2-dependent proliferation and augmented function of NK and T cells from growth factor-mobilized PSC products.
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