EVOLUTION OF BONE-MARROW FIBROSIS AND STROMAL ANTIGENIC EXPRESSION INCHRONIC MYELOID-LEUKEMIA ON ALPHA-INTERFERON AND ARA-C THERAPY

We conducted a retrospective study to assess the changes in bone marro w (BM) stromal antigenic profile and fibrosis in chronic myeloid leuke mia (CML) under combined interferon-alpha (IFN) and Ara-c therapy. Bon e marrow biopsies were taken before therapy and twice (at 4 and 15 mon ths) during therapy in 10 CML patients and compared with non-CML sampl es. Collagen and reticulin fibrosis was assessed by histochemical meth ods and phenotypic changes were studied by immunohistochemistry (APAAP ) with antibodies directed against endothelial cell antigens, cell adh esion molecules, and HLA-DR. It was found that: (1) BM endothelial cel ls in patient and in control specimens showed a specific pattern of an tigen expression: high expression of FVIII and CD34 (except on sinusoi ds for the latter), variable expression of UEA I, and no expression of HLA-DR and E-selectin. (2) Compared to non-CML controls, CML specimen s at diagnosis showed an increased reticulin fibrosis and a decreased expression of CD61 on megakaryocytes and of CD31 on vessels and hemopo ietic cells. (3) Treatment did nor influence BM fibrosis, the vascular content of the BM, or the expression of the antigens tested except an increase in the number of CD34(+) sinusoids (5/10 patients), an incre ase in the number of HLA-DR(+), and a decrease in the number of CD34() hemopoietic cells (6/10). (4) On therapy difficulty in aspiration an d/or reduced BM fragment numbers were noted in 8 of 10 patients whose bone marrow was still normocellular or slightly hypercellular. In conc lusion, CML samples at diagnosis showed increased fibrosis and decreas ed CD31 and CD61 expression compared to controls. During the period of observation, combined therapy did not modify BM fibrosis; however, an increase in CD34(+) sinusoids and a decrease in CD34(+) hemopoietic c ells were noted.