title: Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia.
abstract: OBJECTIVE
  Before the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy.
  
  
  METHODS
  The study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated.
  
  
  RESULTS
  Severe MF (grade II-III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0-I) and severe (grade II-III) groups (p=0.278).
  
  
  CONCLUSIONS
  According to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Pendik Training and Research Hospital, Marmara University, Istanbul, Turkey.
authors.forename: Eda
authors.initials: E
authors.lastname: Tanrikulu Simsek
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ahmet Emre
authors.initials: AE
authors.lastname: Eskazan
authors.affiliation: Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Mahir
authors.initials: M
authors.lastname: Cengiz
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Muhlis Cem
authors.initials: MC
authors.lastname: Ar
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Ekizoglu
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ayse
authors.initials: A
authors.lastname: Salihoglu
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Gulturk
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Tugrul
authors.initials: T
authors.lastname: Elverdi
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Seniz
authors.initials: S
authors.lastname: Ongoren Aydin
authors.affiliation: Department of Pathology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ahu
authors.initials: A
authors.lastname: Senem Demiroz
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ayse Nur
authors.initials: AN
authors.lastname: Buyru
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Baslar
authors.affiliation: Department of Genetics, Institute of Experimental Medicine (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozbek
authors.affiliation: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Koc University, Istanbul, Turkey.
authors.forename: Burhan
authors.initials: B
authors.lastname: Ferhanoglu
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Yildiz
authors.initials: Y
authors.lastname: Aydin
authors.affiliation: Department of Pathology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Nukhet
authors.initials: N
authors.lastname: Tuzuner
authors.affiliation: Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Teoman
authors.initials: T
authors.lastname: Soysal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012155:Reticulin / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D012155:Reticulin; D000068877:Imatinib Mesylate
keywords: CML; HEMATOPATHOLOGY; MYELOFIBROS