In CML, Marrow Fibrosis Relapses or Emerges in 5 - 6 % of Patients Per Year Independently Indicating Imatinib Failure and Shortened Survival Time of Patients.

Imatinib may reverse bone marrow fibrosis (MF) in chronic myeloid leukemia (CML). The risk of emergence or relapse of MF and its prognostic relevance are not known as yet. 110 patients with Ph+ CML recruited in two trials and treated with 400 mg imatinib / day were examined for the risk of MF and its prognostic significance.

Imatinib effectively reversed pretreatment MF (P = 0.0002), and pretreatment fiber increase did not significantly reduce the probability of achieving a hematologic, cytogenetic and major molecular response. However, during a follow-up period of 4 years, small foci with fiber increase (FFI) and MF relapsed in 13 % (5 / 38) of patients, and among patients with an initial normal fiber content (n = 72), FFI emerged in 26 % with transformation to full-blown MF in 38 % of them. FFI occurred in 3 / 27 cases with a major molecular response. The risk of emergence or relapse of FFI amounted to 13.7 % and of full-blown MF to 5.9 % per year, and the risk of acceleration and death increased to 90 % two years after occurrence of MF. FFI could be predicted neither by the risk score (Sokal, Hasford) nor the hematologic, cytogenetic and molecular response, nor by clonal evolution during imatinib treatment. In multivariate analysis, emergence or relapse of FFI and MF turned out to be a significant independent predictor of imatinib failure (P = 0.0003) as well as of acceleration and death of patients (P < 0.0009).

CONCLUSION: Although imatinib reverses initial MF in CML, it does not guarantee against relapse or emergence of MF which affects ~ 6 % of patients per year and therefore, may become a major problem during long-term therapy of CML. Focal evolution of MF should be included in the definitions of imatinib failure and accelerated phase, and continuing imatinib treatment at the current dose is no longer appropriate for patients with emergence of FFI or MF during therapy - regardless of the degree of hematologic, cytogenetic and molecular response.