Reduced total number of cobblestone area forming cells and in vitro stromal-cell growth in autografts from acute myeloid leukemia patients

Background it is well known that ABMT in acute leukemia (AML) often results in delayed hematopoietic engraftment, but the reason behind this has not b een resolved. Previous studies have largely dealt with measurements of comm itted myeloid progenitors as surrogate markers for hematopoiensis. Methods Measurements of week 5 cobblestone area forming cells (CAFC) and st romal-cell growth in BM autografts from 14 AML patients were compared with those from 10 NHL patients. Results Grafts achieved from the AML patients contained a significantly low er total number of CAFC than those from the NHL patients. The reason for th is was a lower total amount of mononuclear cells (MNC) obtained during harv est procedure (mean 0.4 x 10(8)/kg for AML, versus 0.8 x 10(8)/kg for NHL). In contrast, the frequency of CAFC was comparable both between patient gro ups (mean 1.47, range 0.15-6.33 per 10(4) MNC for AML versus mean 1.47 rang e 0.53-3.57 per 10(4) MNC for NHL) and compared with that of eight normal d onors (mean 1.12, range 0.73-1.73 per 10(4) MNC). An inverse relationship w as observed between the total CAFC number in the grafts and the hematopoiet ic reconstitution of both granulocytes greater than or equal to 2.0 x 10(9) /L and thrombocytes greater than or equal to 50 x 10(9)/L, in which the lev el of 9.0 x 10(3) CAFC/kg implied a prompt engraftment for both patient gro ups. Whereas the stromal cell outgrowth in vitro from 8/10 NHL patients was similar tot that of six normal donors, only a few stromal cells appeared i n the majority of nine evaluable AML patients. Discussion A decreased total CAFC content, as well as inferior stromal-cell function, may well be critical elements for prolonged hematopoietic recons titution in AML.