HIGH-DOSE THERAPY WITH PERIPHERAL-BLOOD PROGENITOR-CELL SUPPORT IN PATIENTS WITH NON-HODGKINS-LYMPHOMA

Between September 1991 and April 1995, high-dose therapy with peripher al blood progenitor cell(PBPC) support was administered to 105 patient s with non-Hodgkin's lymphoma (NHL). Thirty-three patients had high-gr ade NHL, while 72 patients had different forms of low- or interme diat e-grade NHL. Except for three patients who received G-CSF during stead y-state hematopoiesis, PBPCs were collected following cytokine-support ed cytotoxic chemotherapy. This included G-CSF or the sequential admin istration of interleukin 3 (IL-3) and GM-CSF, Assessing bone marrow (B R3) samples before the start of chemotherapy and leukapheresis (LP) pr oducts collected during cytokine-enhanced marrow recovery, a 2.3-fold greater mean concentration of CD34(+) cells was found in peripheral bl ood (p < 0.005), The blood-derived progenitor cells were enriched with a particular subset of more primitive progenitors, as the mean propor tion of CD34(+)/Thy-1(+) cells in LP products was three-fold greater i n comparison to premobilization BM samples, respectively (p < 0.001), In contrast, the mean proportion of CD34(+)/CD19(+) and CD19(+) cells in LP products was 8.8- and 80-fold smaller compared to BM samples, re spectively (p < 0.001). Following high-dose conditioning therapy inclu ding TBT in 74 patients, reinfusion of PBPC resulted in rapid and sust ained engraftment in the majority of patients, while in seven patients an unsubstituted platelet count of greater than 20 x 10(9)/l was reac hed between 31 and 51 days, Five patients died of treatment-related co mplications between 13 and 188 days following transplantation. The pro bability of long-term disease-free survival at 30 months in patients a utografted while they were in first remission was 70% in high-grade an d 83% in low-grade NHL, respectively. The data may provide the rationa le for the use of PBPC-supported high-dose regimens as first-lint trea tment for patients at high risk of treatment failure.