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

Abstract

It is well known that ABMT in acute myeloid leukemia (AML) often results in delayed hematopoietic engraftment, but the reason behind this has not been resolved. Previous studies have largely dealt with measurements of committed myeloid progenitors as surrogate markers for hematopoiesis. Measurements of Week 5 cobblestone area forming cells (CAFC) and stromal-cell growth in BM autografts from 14 AML patients were compared with those from 10 NHL patients. Grafts achieved from the AML patients contained a significantly lower total number of CAFC than those from the NHL patients. The reason for this was a lower total amount of mononuclear cells (MNC) obtained during harvest 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 groups (mean 1.47, range 0.15-6.33 per 10(4) MNC for AML versus mean 1.47, range 0.53-3.57 per 10(4) MNC for NHL) and compared with that of eight normal donors (mean 1.12, range 0.73-1.73 per 10(4) MNC). An inverse relationship was observed between the total CAFC number in the grafts and the hematopoietic reconstitution of both granulocytes > or = 2.0 x 10(9)/L and thrombocytes > or = 50 x 10(9)/L, in which the level of 9.0 x 10(3) CAFC/kg implied a prompt engraftment for both patient groups. Whereas the stromal cell outgrowth in vitro from 8/10 NHL patients was similar to that of six normal donors, only a few stromal cells appeared in the majority of nine evaluable AML patients. A decreased total CAFC content, as well as an inferior stromal-cell function, may be critical elements for prolonged hematopoietic reconstitution in AML.