THE IMPACT OF INTERFERON VERSUS BUSULFAN THERAPY ON THE RETICULIN STAIN-MEASURED FIBROSIS IN CML - A COMPARATIVE MORPHOMETRIC STUDY ON SEQUENTIAL TREPHINE BIOPSIES

To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph(1+)-CML, a clinicopathological study was performed on s equential trephine biopsies of the bone marrow following either interf eron (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver i mpregnation method, number of megakaryocytes and density of ar gyrophi lic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who h ad received BU. In both groups, repeated bone marrow biopsies (total 1 25) revealed a significant increase in the fiber content, as well as i n the number of megakaryocytes during treatment. To assess the dynamic s of myelofibrosis more precisely, computation of differences in the d egree of fiber density between the first and last examination was carr ied out. Regarding the considerable variations in the biopsy intervals , a so-called myelofibrosis progression index (MPI) was calculated. Fo llowing this rationale, we were able to demonstrate that, in compariso n to the BU-group, speed of progression of bone marrow fibrosis was si gnificantly increased in CML patients treated with IFN. Preliminary st atistical analysis indicated a relationship between myelofibrosis on a dmission, which was always associated with increased growth of megakar yocytes, and the MPI with survival. Even when these parameters were re garded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelof ibrosis may be related to several conversely acting pathomechanisms. A mong others, the inability of both therapeutic agents to reduce the nu mber of megakaryocytes more effectively should be taken into considera tion.