Objectives: 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.
Keywords: Bone marrow fıbrosis; TKI drugs.