Bone marrow fibrosis grade is an independent risk factor for overall survival in patients with primary myelofibrosis

Li, B; Zhang, P; Gu, Feng; Xu, Zefeng; Qin, Tiejun; Zhang, Y; Sha, Zhiqiang; Dong, Diansheng; Zhang, H; Fang, Liwei; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang; Cai, Wenyu; Huang, Gang; Xiao, Zhijian

doi:10.1038/bcj.2016.116

Cited by 10 publications

(5 citation statements)

References 14 publications

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“…BMF is a key histopathological feature and major diagnostic criterion of myelofibrosis and is characterized by increased deposition of reticulin and/or collagen fibers secondary to aberrant immature megakaryocytes, which release excessive amounts of inflammatory and fibrogenic cytokines [3,6,[29][30][31]. Bone marrow biopsies are evaluated and scored using updated World Health Organization criteria consisting of 4 escalating grades of severity: grade 0-3 [32].…”

Section: Jak Inhibitors Have Been the Mainstay Of Myelofibrosis Treat...mentioning

confidence: 99%

“…BMF grading, while not incorporated in conventional prognostic score systems (International Prognostic Scoring System [IPSS] or Dynamic International Prognostic Scoring System [DIPSS]), does form part of the more recent Mutation‐Enhanced International Prognostic Scoring System 70 and 70‐plus (MIPPS70 and MIPPS70+) [3, 33]. Clinical studies have associated higher grades of BMF with poor prognosis [29, 34, 35]. Recent studies have reported BMF improvement as evidence of disease modification, and BMF change or reversal has been pursued as an endpoint in clinical trials, including after allogeneic transplantation [4, 36–39].…”

Section: Introductionmentioning

confidence: 99%

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Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis

Oh,

Verstovsek,

Gupta

et al. 2024

eJHaem

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Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor–naive patients from SIMPLIFY‐1 (NCT01969838), a double‐blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of ≥1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with ≥1‐grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.

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Section: Jak Inhibitors Have Been the Mainstay Of Myelofibrosis Treat...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis

Oh,

Verstovsek,

Gupta

et al. 2024

eJHaem

View full text Add to dashboard Cite

show abstract

“…Studies have shown that CALR mutations favour overall survival in PMF patients, while MPL mutations are not detrimental to overall survival [ 33 , 34 ]. In addition to driver mutations, undetected MPN driver mutations and myelofibrosis are independent risk factors for survival in PMF patients [ 35 , 36 ]. On the other hand, with the update of the PMF prognostic system, non-driver mutations such as ASXL1, EZH2, SRSF2, IDH1/2 and other genetic variants in PMF patients are also high-risk factors affecting PMF patients [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Immunophenotype of myeloid granulocytes in Chinese patients with BCR::ABL1-negative myeloproliferative neoplasms

Liang,

Pan

et al. 2024

Clin Exp Med

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Typical BCR::ABL1-negative myeloproliferative neoplasms (MPN) are mainly referred to as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofbrosis (PMF). Granulocytes in MPN patients are involved in their inflammation and form an important part of the pathophysiology of MPN patients. It has been shown that the immunophenotype of granulocytes in MPN patients is altered. We used flow cytometry to explore the immunophenotype of MPN patients and correlate it with clinical parameters. The results showed that PMF patients and PV patients had higher CD15+CD11b+ granulocytes than ET patients and normal controls. When grouped by gene mutation, changes in the granulocyte immunophenotype of MPN patients were independent of the JAK2V617F and CALR mutations. There was no significant heterogeneity in immunophenotype between ET patients and Pre-PMF, and between Overt-PMF and Pre-PMF patients. Granulocytes from some MPN patients showed an abnormal CD13/CD16 phenotype with a significant increase in mature granulocytes on molecular and cytomorphological grounds, and this abnormal pattern occurred significantly more frequently in PMF patients than in ET patients. CD15–CD11b– was negatively correlated with WBC and Hb and positively correlated with DIPSS score, whereas high CD10+ granulocytes were significantly and negatively associated with prognostic system IPSS and DIPSS scores in PMF patients. In conclusion, this study demonstrates the landscape of bone marrow granulocyte immunophenotypes in MPN patients. MPN patients, especially those with PMF, have a significant granulocyte developmental overmaturation phenotype. CD10+ granulocytes may be involved in the prognosis of PMF patients.

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“…The bone marrow brosis grade 2 to grade 4 was associated with worse overall survival in our study. The accurate evaluation of bone marrow brosis has been highlighted to be a key point to predict prognosis in PMF [33]. Guglielmelli et al showed that there was a correlation between the higher grades of brosis and survival despite the IPSS variables and mutational status [34].…”

Section: Discussionmentioning

confidence: 99%

The mortality outcomes and survival pattern of patients of Myeloproliferative Neoplasms in Malaysia

Yap¹,

Sathar²,

Law

et al. 2021

Preprint

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Background: The prognostication of myeloproliferative neoplasm (MPN) has always been challenging even in the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of MPN in a developing country such as Malaysia is still undetermined.Materials and Methods: This was a retrospective study using information from 774 patients from the National MPN Registry conducted from the year 2009 to 2015 in Malaysia. Patients with the diagnosis of essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U) were included. Survival data were traced until December 2018. Results: The cohort consisted of 42.0% ET, 41.0% PV, 8.9% PMF and 8.1% MPN-U, with 48.8% Malay, 39.1% Chinese, 7.1% Indian, 5.0% Others. The subtypes analysis revealed that male MPNs was more than female MPNs except in ET. The Chinese ethnicity was associated with the highest incidence of ET. The mortality rate was the highest in PMF followed by MPN-U then PV and ET (p<0.0001). Survival analysis revealed that the overall survival differed significantly according to characteristics such as sex, sub-types, JAK2 V617F mutation, bone marrow fibrosis, presence of splenomegaly, diabetes mellitus, hypertension, and bleeding manifestation. Cox regression analysis identified age, haemoglobin level, sex, and subtype as a significant risk factor for mortality outcome. Conclusion: Patients with ET had the slightly better OS while PMF had the worst OS. This is in conjunction with low haemoglobin, worsening bone marrow fibrosis, splenomegaly, diabetes mellitus, hypertension and bleeding. JAK2 V617F mutation was seemingly resulting in inferior overall survival especially in ET and PMF. The survival outcome of the MPN registry is instrumental for future policy development of effective healthcare in Malaysia.

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Bone marrow fibrosis grade is an independent risk factor for overall survival in patients with primary myelofibrosis

Cited by 10 publications

References 14 publications

Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis

Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis

Immunophenotype of myeloid granulocytes in Chinese patients with BCR::ABL1-negative myeloproliferative neoplasms

The mortality outcomes and survival pattern of patients of Myeloproliferative Neoplasms in Malaysia

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