Myelofibrosis in Patients of Chronic Myeloid Leukemia in Chronic Phase at Presentation

Hamid, Ambareen; Ashraf, Sobia; Qamar, Samina; Naveed, Muhammad Asif; Hameed, Asifa; Farooq, Muhammad

doi:10.29271/jcpsp.2019.11.1096

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…However, as the grading of MF seems to vary significantly depending on the individual assessment, another, possibly technology-aided and centralized approach to grade fibrosis in the BM would help to reduce the variations seen in different studies ( Gralnick et al, 1971 ; Kvasnicka et al, 2001 ; Buesche et al, 2003 ; Hamid et al, 2019 ). One major limitation of our study is that in our cohort, only a small number of patients in TFR could be included.…”

Section: Discussionmentioning

confidence: 99%

“…The severity of BM fibrosis is often described with MF grades ranging from lower prefibrotic grade 1 to defined MF with grades 2–3 ( Thiele et al, 2005 ; Swerdlow et al, 2017 ). In CML, the proportion of patients with MF varies widely from 30% to 100% of patients ( Gralnick et al, 1971 ; Kvasnicka et al, 2001 ; Buesche et al, 2003 ; Hamid et al, 2019 ). 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 ).…”

Section: Introductionmentioning

confidence: 99%

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

Jacobi,

Vieri,

Bütow

et al. 2023

Front. Pharmacol.

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The management of patients with chronic myeloid leukemia (CML) has been revolutionized by the introduction of tyrosine kinase inhibitors (TKIs), which induce deep molecular responses so that treatment can eventually be discontinued, leading to treatment-free remission (TFR) in a subset of patients. Unfortunately, leukemic stem cells (LSCs) often persist and a fraction of these can again expand in about half of patients that attempt TKI discontinuation. In this study, we show that presence of myelofibrosis (MF) at the time of diagnosis is a factor associating with TFR failure. Fibrotic transformation is governed by the action of several cytokines, and interestingly, some of them have also been described to support LSC persistence. At the cellular level, these could be produced by both malignant cells and by components of the bone marrow (BM) niche, including megakaryocytes (MKs) and mesenchymal stromal cells (MSCs). In our cohort of 57 patients, around 40% presented with MF at diagnosis and the number of blasts in the peripheral blood and BM was significantly elevated in patients with higher grade of MF. Employing a CML transgenic mouse model, we could observe higher levels of alpha-smooth muscle actin (α-SMA) in the BM when compared to control mice. Short-term treatment with the TKI nilotinib, efficiently reduced spleen weight and BCR::ABL1 mRNA levels, while α-SMA expression was only partially reduced. Interestingly, the number of MKs was increased in the spleen of CML mice and elevated in both BM and spleen upon nilotinib treatment. Analysis of human CML-vs healthy donor (HD)-derived MSCs showed an altered expression of gene signatures reflecting fibrosis as well as hematopoietic support, thus suggesting MSCs as a potential player in these two processes. Finally, in our cohort, 12 patients qualified for TKI discontinuation, and here we observed that all patients who failed TFR had BM fibrosis at diagnosis, whereas this was only the case in 25% of patients with achieved TFR, further supporting the link between fibrosis and LSC persistence.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Jacobi,

Vieri,

Bütow

et al. 2023

Front. Pharmacol.

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“…Among other specific chronic toxicities related to the drug, late occurrence of moderate/severe anemia during long-lasting treatment with imatinib has been reported in a moderate rate of patients and seems to be more common in elderly [5]. It has been recently shown that bone marrow fibrosis is very common in CML patients at diagnosis (65% have grade 1 and 27% grade 2) [6], and that patients with two or more chromosomal abnormalities in Ph'-negative cells (including those that are related to clonal hematopoiesis or myelodysplasia) showed sometimes worse response to TKIs [7]. Thus, several factors could be responsible for developing anemia during imatinib, but its pathogenesis is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin treatment in chronic phase chronic myeloid leukemia patients treated with frontline imatinib who developed late anemia

Cesini

Frieri

Baratè

et al. 2020

European J of Haematology

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Background Role of erythropoietin (EPO) in the treatment of late anemia in patients with Chronic Myeloid Leukemia (CML) is still undefined. Methods Fifty CML patients treated at 14 Institutions with frontline imatinib for at least 12 months and in stable complete cytogenetic response who developed a late chronic anemia treated with EPO were retrospectively evaluated. ResultsMedian time from imatinib start to EPO treatment was 42.2 months [interquartile range (IQR) 20.8 -91.9]. Median Hb value at EPO starting time was 9.9 g/dl (IQR 8.9 -10.3): eleven patients (22.0%) were transfusion dependent. Alpha-EPO (40,000 UI weekly) was employed in 37 patients, beta-EPO (30,000 UI weekly) in 9 patients, zeta-EPO (40,000 UI weekly) in 2 patients and darbopoietin (150 mcg/weekly) in the remaining 2 patients. On the whole, 41 patients (82.0%) achieved an erythroid response, defined as a stable (> 3 months) improvement > 1.5 g/dl of Hb level, and 9 patients (18.0%) indeed resulted resistant. Among responding patients, 10 relapsed after a median time from EPO start of 20.7 months . No EPO-related toxicity was observed.Conclusions Results of EPO treatment for late chronic anemia during long-lasting imatinib therapy are encouraging, with a high rate of response.

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Prognostic Impact of Bone Marrow Fibrosis and Effects of Tyrosine Kinase Inhibitors on Bone Marrow Fibrosis in Chronic Myeloid Leukemia

Pepeler,

Tıglıoglu,

Dagdas

et al. 2024

Clinical Lymphoma Myeloma and Leukemia

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Myelofibrosis in Patients of Chronic Myeloid Leukemia in Chronic Phase at Presentation

Abstract: Objective: To determine the frequency and grading of myelofibrosis in patients of chronic myeloid leukaemia in chronic phase, and the association of cytopenias/cytosis with the degree of fibrosis. Study Design: Descriptive study.

Cited by 3 publications

References 18 publications

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

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

Erythropoietin treatment in chronic phase chronic myeloid leukemia patients treated with frontline imatinib who developed late anemia

Prognostic Impact of Bone Marrow Fibrosis and Effects of Tyrosine Kinase Inhibitors on Bone Marrow Fibrosis in Chronic Myeloid Leukemia

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