title: Bone marrow fibrosis may be an effective independent predictor of the 'TKI drug response level' in chronic myeloid leukemia.
abstract: OBJECTIVE
  The aim of this study was to assess bone marrow (BM) fibrosis and dysplasia in chronic myeloid leukemia (CML) patients receiving the first-generation tyrosine kinase inhibitor (TKI), imatinib, or second-generation TKIs, dasatinib, and nilotinib. We further investigated whether CML under TKI is associated with dysplastic BM changes during the clinicopathological course of the disease.
  
  
  METHODS
  In total, pre-treatment BM paraffin blocks of biopsy specimens were available for 41 adult patients diagnosed with chronic phase CML. Post-treatment BM aspirate clot and core biopsy samples were reviewed for fibrosis and dyshematopoiesis.
  
  
  RESULTS
  Overall, 13 (31.7%) patients achieved a complete cytogenetic response with imatinib treatment, with no events. In 25 patients, imatinib was discontinued owing to primary or secondary resistance. In patients with initial dysmyelopoiesis, the rate of BM fibrosis was 82.4 versus 47.6% for other patient groups (P = 0.02). Overall, 24 patients with newly diagnosed CML showed marrow fibrosis, among which 19 (79.1%) had imatinib resistance. However, only 5 out of 15 patients (33.5%) without marrow fibrosis had imatinib resistance (P = 0.08). Discussion Our findings indicate that BM fibrosis is an independent predictor of the 'TKI drug response level' in CML and support its inclusion as a critical pathobiological parameter for decision-making with regard to TKI drug selection de novo, calculation of prognosis at the onset of disease, and monitoring response to TKI in the long-term disease course of CML.
authors.forename: Eylem
authors.initials: E
authors.lastname: Eliacik
authors.forename: Ayse
authors.initials: A
authors.lastname: Isik
authors.forename: Cisel
authors.initials: C
authors.lastname: Aydin
authors.forename: Aysegul
authors.initials: A
authors.lastname: Uner
authors.forename: Salih
authors.initials: S
authors.lastname: Aksu
authors.forename: Nilgun
authors.initials: N
authors.lastname: Sayinalp
authors.forename: Haluk
authors.initials: H
authors.lastname: Demiroglu
authors.forename: Hakan
authors.initials: H
authors.lastname: Goker
authors.forename: Yahya
authors.initials: Y
authors.lastname: Buyukasik
authors.forename: Osman
authors.initials: O
authors.lastname: Ozcebe
authors.forename: Ibrahim C
authors.initials: IC
authors.lastname: Haznedaroglu
mesh_terms: D000328:Adult; D000368:Aged; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage* / Q000009:adverse effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D038042:Myelopoiesis / Q000187:drug effects*; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000068877:Imatinib Mesylate
keywords: Bone marrow fıbrosis; TKI drugs