Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia

Abstract

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.

Myelofibrosis at diagnosis is associated with the failure of treatment-free remission in CML patients

“…BM fibrosis at diagnosis has been shown to revert in the majority of patients upon TKI treatment (Buesche et al, 2007;Eliacik et al, 2015;Narang et al, 2017) and we likewise observed this in patient 11. Tanrikulu Simsek et al (2016) furthermore confirmed a decrease in fibrosis grades after long-time imatinib treatment. It has to be noted that in a few single patients imatinib treatment was associated with induction of BM fibrosis (Buesche et al, 2007;Shanmuganathan et al, 2019) and interestingly, in patient 3 of our cohort we see development of low-grade fibrosis after 5.5 years of imatinib treatment.…”

“…First, we could observe that in our cohort around 40% of the patients presented with MF at diagnosis and MF grade 2 correlated with higher blast counts in the blood and BM. Although the impact of BM fibrosis on prognosis was considered adverse in the pre-TKI era ( Lazzarino et al, 1986 ; Kvasnicka et al, 2001 ; Buesche et al, 2003 ), it seems to be less relevant nowadays, due to the enormous success of TKIs and the drastic improvements in patient management that were introduced ( Kantarjian et al, 2005 ; Tanrikulu Simsek et al, 2016 ). BM fibrosis at diagnosis has been shown to revert in the majority of patients upon TKI treatment ( Buesche et al, 2007 ; Eliacik et al, 2015 ; Narang et al, 2017 ) and we likewise observed this in patient 11.…”

“…Interestingly, imatinib seems to be able to either slow down or reverse MF ( Beham-Schmid et al, 2002 ; Bueso-Ramos et al, 2004 ; Thiele et al, 2004 ; Buesche et al, 2007 ). An open question is whether the degree of MF at diagnosis has an impact on response to TKI treatment, with different studies showing conflicting results ( Kantarjian et al, 2005 ; Buesche et al, 2007 ; Tanrikulu Simsek et al, 2016 ). Importantly, Buesche et al (2007) showed that MF before start or within the first 3 months of imatinib therapy did not influence the probability of achieving a complete hematologic response during imatinib treatment.…”