Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

High-dose chemotherapy with autologous stem cell rescue has been proposed a s an intensive therapy for severe rheumatoid arthritis (RA). In view of pre vious observations of abnormal haemopoiesis in RA patients, the composition and function of peripheral blood stem cell harvests (PBSCH) was investigat ed. Compared with PBSCH from healthy allogeneic donors mobilized with the s ame dose of G-CSF (filgrastim; 10 mu g/kg/d, n = 14). RA PBSCH (n = 9) cont ained significantly fewer mononuclear cells (375 v 569 x 10(6)/kg, P = 0.03 ) and CD34(+) cells (2.7 v 5.8 x 10(6)/kg, P = 0.003). However, there were increased proportions of CD14(+) cells (P = 0.006) and CD14(+)CD15(+) cells (the phenotype of pre previously described 'abnormal' myeloid cells, P = 0 .002) in the RA PBSCH which translated into 3.5- and 7-fold increases respe ctively on a per CD34(+) cell basis. There were no differences in T-cell ac tivation status as judged by proportions of CD4(+) and CD8(+) expressing CD 45RA, CD45RO, HLA-DR and CD28 (RA PBSCH, n = 7, donor PBSCH, n = 5, P = 0.2 -0.7). Phytohaemagglutinin responses determined fluorocytometrically with i nduction of CD69 expression were reduced in CD4(+) and CD8+ cells following filgrastim administration in 3/3 RA patients tested. Compared with bone ma rrow as a potential source of CD34(+) cells, PBSCH contained 11-fold more T cells (P < 0.0005), 8-fold more B cells (P < 0.0005) and 4-fold more monoc ytes (P = 0.02). In short-term methylcellulose culture there were no differ ences in colony counts (CFU-GM, CFU-GEMM, BFU-E) per CD34(+) cell from PBSC H from RA patients (n = 11) and healthy donors (n = 10). Long-term culture initiator cells were cultured successfully from cryopreserved PBSCH from RA patients (n = 9). In conclusion, PBSCH from RA patients differed significa ntly in composition from normal individuals, but in vitro studies support n ormal stem and progenitor cell function, Changes in T-cell function occur d uring mobilization in RA patients. This work provides reassurance for the u se of PBSCH as haematological rescue and baseline data for clinical trials of graft manipulation strategies in patients with RA.