Significance of Marrow Fibrosis in Chronic Phase Chronic Myelogenous Leukemia (CML) Post Interferon-A Failure Treated with Imatinib Mesylate Therapy.

Background. Myelofibrosis in the setting of CML has been historically associated with poor prognosis and with transformation. Its significance in the context of imatinib therapy is unknown.

Study Aims. To evaluate the prognostic relevance of myelofibrosis in patients with chronic phase CML post interferon-a failure treated with imatinib.

Patients and Methods. 110 patients with Philadelphia chromosome (Ph)-positive CML were analyzed. Imatinib was given at 400 mg orally daily. Marrow biopsies obtained prior to imatinib were subjected to Snook’s reticulin staining and graded on a scale of 1 to 4 for the degree of reticulin fibrosis as previously reported (Dekmezian.Cancer 59:1739, 1987). Severe fibrosis included grades 3–4.

Results. Patients’ median age was 57 years (24 to 81). Median duration of chronic phase was 31 months (range 6–148). Reticulin fibrosis was grade 1 in 4%, grade 2 in 35%, grade 3 in 28% and grade 4 in 33%. Splenomegaly was more frequent with grade 3–4 fibrosis (p=0.04). However, patients with severe fibrosis had a similar incidence of complete cytogenetic response and survival as those with lesser degrees of fibrosis.

Conclusions. Imatinib, being a highly effective therapy in CML, may have reduced or eliminated the previously known prognostic impact of myelofibrosis in CML.