Therapy-related changes of the bone marrow in chronic idiopathic myelofibrosis

Histol Histopathol. 2004 Jan;19(1):239-50. doi: 10.14670/HH-19.239.

Abstract

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.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biopsy
  • Bone Marrow / drug effects
  • Bone Marrow / pathology*
  • Busulfan / therapeutic use
  • Chronic Disease
  • Drug Therapy, Combination
  • Follow-Up Studies
  • Humans
  • Hydroxyurea / therapeutic use
  • Interferons / therapeutic use
  • Primary Myelofibrosis / drug therapy*

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Interferons
  • Busulfan
  • Hydroxyurea