1. ¹Institut für Pathologie, Medizinische Hochschule, Hannover, Germany
2. ²Klinik für Hämatologie, Hämostaseologie und Onkologie, Medizinische Hochschule, Hannover, Germany
3. ³Institut für Zell- und Molekularpathologie, Medizinische Hochschule, Hannover, Germany
4. ⁴Institut für Biometrie, Medizinische Hochschule, Hannover, Germany

Correspondence: Dr G Buesche, Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. E-mail: guntram.buesche@arcor.de

Received 19 April 2006; Revised 7 July 2007; Accepted 20 July 2007; Published online 6 September 2007.

Abstract

In chronic myeloid leukemia (CML), imatinib may reverse bone marrow fibrosis (MF). Whether the unfavorable prognosis of MF is also reversed and whether imatinib guarantees against evolution of MF are unclear as yet. Fifty-nine patients with Ph⁺ CML treated with 400 mg imatinib/day were examined for MF in 6- to 12-month intervals. Imatinib effectively reversed initial MF (P<0.0005). However, during a follow-up period of up to 4.8 years, small foci with abnormal fiber increase (FFI) emerged in 8 of 30 pretreated and 6 of 29 non-pretreated patients. Patients with FFI showed a significantly lower probability of achieving a complete cytogenetic or major molecular response (36 versus 81%; P<0.007). During the further follow up, 57% of patients with FFI but none of the other patients suffered from full-blown MF (P=0.00005). None of the patients with FFI or MF showed a Janus kinase-2 mutation (V617F). Evolutions of FFI and MF were independent significant predictors of imatinib failure (P=0.0031), accelerated phase and death of patients (P=0.0001; multivariate analyses). Imatinib effectively reverses initial MF in CML, but neither eliminates its unfavorable prognosis nor guarantees completely against new evolution of MF.