Comparative Effects of Interferon and Hydroxyurea on Bone Marrow Fibrosis in Chronic Myelogenous Leukemia

Abstract

Therapy-related changes of the bone marrow fiber content remain a controversial issue in hematopathology. This conflict of opinion firstly depends on difficulties to determine the quantity of fibers exactly (semiquantitative grading, morphometry, reference to cellularity). Secondly, the appropriate selection of patients with specific monotherapies including hydroxyurea (HU) and interferon-α (IFN) seems to present some problems. Finally, assessment of myelofibrosis is further biased by the different endpoints of sequential examinations. The latter shortcoming can be improved upon by the calculation of the myelofibrosis progression/regression index which describes the ratio between difference of fiber density and observation time. Using strictly defined therapeutic regimens and intervals between sequential trephine biopsies a stimulating effect of IFN administration on bone marrow fibrosis in Ph¹⁺-chronic myelogenous leukemia (CML) has been found. This result is comparable with the failure of this agent to improve myelofibrosis (and splenomegaly) in a considerable number of patients with allied subtypes of chronic myeloproliferative disorders. This is in contrast to the effect HU exerts which is a more fibrolytic or even stabilizing influence on bone marrow fibrosis. This phenomenon is readily demonstrable by the assessment of dynamic features (myelofibrosis progression index). In addition, patients showing a rapid progression of myelofibrosis during IFN and HU treatment of Ph¹⁺-CML are generally associated with a poor risk outcome and a significant worsening of survival.

Key Words:

• chronic myelogenous leukemia
• myelofibrosis
• interferon
• hydroxyurea
• dynamics of fibrosis