In chronic
myeloproliferative disorders (CMPDs) a conflict of opinion exists regarding
therapy-induced bone marrow (BM) changes and the evolution of
myelofibrosis during the lengthy course of the disease. For a more elaborate study of these features
chronic idiopathic myelofibrosis (IMF) seems to be a most suitable condition. Therefore this review is focused on this CMPD and amongst other findings analyzes data from a series of 340 patients with a long follow-up including 893 biopsies (median interval of 32 months). The ensuing results were compared with those communicated in the relevant literature. In addition to a control group of 153 patients with IMF who received only symptomatic treatment,
therapy groups included
busulfan,
hydroxyurea,
interferon and various combinations. In all groups hypoplasia of a varying degree was a frequent finding (6%) and often accompanied by a patchy arrangement of hematopoiesis. Most conspicuous was a gelatinous
edema showing a tendency to develop a discrete
reticulin fibrosis (
scleredema). Aplasia developed in 7.7% of patients, usually at terminal stages of the disease independently of treatment. Minimal to moderate maturation defects of hematopoiesis involved especially megakaryocytes and erythroid precursors, but overt myelodysplastic features were most prominent following
hydroxyurea and
busulfan therapy. Acceleration and blastic crisis were characterized not only by increasing dysplastic changes, but also by the appearance of blasts including CD34+ cells. Semiquantitative grading of the fiber content revealed that 183 patients (54%) without or with moderate
fibrosis at the beginning showed a significant progression and therefore contrasted with the 66 patients with a stable state. Following this calculation no relevant differences in the evolution of
myelofibrosis were evident in the various
therapy groups especially not following
interferon treatment. In a few patients a regression was found which was accompanied by a severe hypoplasia or aplasia compatible with a myelo-ablative effect. In conclusion, peculiar BM changes, in particular conspicuously expressed myelodysplastic features are consistent with
therapy-related lesions. Development of
myelofibrosis in IMF is obviously due to
disease progression unrelated to stage at diagnosis and not significantly influenced by treatment modalities.