Imatinib Mesylate Reduces Bone Marrow Fibrosis and Overwhelms the Adverse Prognostic Impact of Reticulin Formation in Patients with Chronic Myeloid Leukemia

• Published in: Blood 2015-12, Vol.126 (23), p.2783-2783
• Main Authors: Tanrikulu Simsek, Eda, Eskazan, Ahmet Emre, Cengiz, Mahir, Ar, M. Cem, Ekizoglu, Seda, Salihoglu, Ayse, Gulturk, Emine, Elverdi, Tugrul, Ongoren Aydin, Seniz, Demiroz, Ahu Senem, Buyru, Ayse Nur, Baslar, Zafer, Ozbek, Ugur, Ferhanoglu, A. Burhan, Aydin, Yildiz, Tuzuner, Nukhet, Soysal, Teoman
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.2783.2783

Introduction: Imatinib mesylate (IM) is the first tyrosine kinase inhibitor (TKI) licensed for the treatment of chronic myeloid leukemia (CML). Severe bone marrow fibrosis (BMF) has been reported in excess of 40% of the patients with CML at diagnosis. Before TKIs became available, BMF which emerged at diagnosis and/or in the late periods of the disease was defined to be a poor prognostic factor, and it contributed significantly to morbidity and mortality from 10% to 30% in patients with CML. The relationship between BMF and both disease progression and prognosis has been the subject of re-evaluation after the introduction of IM therapy. In patients with CML, it has not been clearly demonstrated yet, whether IM improves the poor prognostic effect of fibrosis, and prevents the new BMF development or not. Aim: The purpose of this study was to evaluate the effects of IM therapy on BMF formation, and the prognostic significance of BMF in patients with CML. Material and Methods: One hundred and thirty-five CML patients were enrolled in the study. Patients' demographics, Sokal risk scores, molecular and cytogenetic responses and follow-up periods were noted from the patients' files retrospectively. All pre- and post-IM bone marrow biopsy samples, which were stained with hematoxylin and eosin, were re-evaluated for the current analysis. Grading of BMF was according to the European consensus decisions, graded as 0-III. The term "last bone marrow biopsy" (LBMB) is referred to a biopsy, which was performed at 18th months or later on during IM treatment. Results: The median age was 44 years (range, 18-92 years), and 78 patients (58%) were male. One hundred and twenty-eight patients (95%) were in chronic phase [CP], 4 patients (3%) were in accelerated phase [AP], and 3 patients (2%) were in blast crisis [BC] at the time of IM initiation. Out of 128 CML-CP patients, one hundred and twenty patients (93%) were in early CP, whereas 8 (7%) were in late CP. The percentage of low, intermediate, and high Sokal risk scores were 35%, 43%, and 22%, respectively. Before IM was initiated, thirty-one patients had received previous treatment modalities (hydroxyurea (HU) in twenty-one, and 10 patients had received interferon plus HU. he median duration of IM treatment was 45 months (range, 2-106 months). The rates of complete hematological response (CHR) at 3rd month, complete cytogenetic response (CCyR) at 12th month, and major molecular response (MMR) at 18th month were 92.4%, 71.6%