Stroma-supported progenitor production as a prognostic tool for graft failure following autologous stem cell transplantation

To analyse the involvement of a possible numerical or qualitative stem cell defect in the development of sustained graft failure after autologous tran splantation, we have determined the graft content of CD34(+) nucleated cell s, colony-forming cells and cobblestone area-forming cell subsets, as well as transplant ability to produce progenitors using the long-term culture co lony-forming cell (LTC-CFC) assay. We evaluated material from the graft ref erence ampoules of 13 graft failure patients after bone marrow transplantat ion (BMT), four graft failure patients and four isolated thrombocytopenia p atients after peripheral blood stem cell transplantation (PBSCT). We compar ed these data with those from six successfully engrafted BMT patients and 2 0 engrafted PBSCT patients respectively. In the BMT setting, the LTC-CFC 6- week assay represented a highly significant graft failure predictor. In the PBSCT setting, the total number of 2-week and 6-week LTC-CFCs transplanted per kg bodyweight (BW) showed the highest significant difference between t he engrafted and the graft failure patients, as well as between the engraft ed patients and the patients suffering from isolated thrombocytopenia after transplantation. These data show that the ability of a graft to generate p rogenitors in vitro rather than the number of primitive progenitors transpl anted can have prognostic value for post-transplant haematological reconsti tution.