The impact of bone marrow fibrosis and JAK2 expression on clinical outcomes in patients with newly diagnosed multiple myeloma treated with immunomodulatory agents and/or proteasome inhibitors

Paul, Barry; Zhao, Yue; Loitsch, Gavin; Feinberg, Daniel; Mathews, Parker; Dupuis, Megan; Li, Zhiguo; Rein, Lindsay; Wang, Endi; Kang, Yubin

doi:10.1002/cam4.3265

Cited by 8 publications

(5 citation statements)

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“…Recently, in a study by Paul et al , out of 393 patients, 48.2% (122 patients) had bone marrow fibrosis at presentation and concluded that the patients with bone marrow fibrosis had poor outcome despite proteosome inhibitor therapy and immunomodulatory therapy. 8 In a study by Slany et al , in the multifactorial development of plasma cell myeloma from MGUS, fibroblast like cells are one of the critical factors. Comparative proteome profiling of isolated fibroblast like cells in patients of MGUS, myeloma and control patients were performed and indicated that extracellular matrix remodelling already begins at MGUS and becomes pronounced in myeloma.…”

Section: Discussionmentioning

confidence: 99%

Clinico-pathological profile of patients with plasma cell neoplasms with special reference to bone marrow fibrosis and amyloid deposition

Kannan,

Dass,

Dangudubiyyam

et al. 2023

J Clin Exp Hematopathol

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To clarify the significance of bone marrow fibrosis and amyloid deposition in plasma cell neoplasm, a retrospective cross-sectional study for a period of 3 years was conducted. Patients who underwent bone marrow aspiration and biopsy with suspicion of plasma cell neoplasms were included in the study. The bone marrow findings were correlated with clinical profile of the patient along with biochemical parameters, cytogenetics, Fluorescent in situ hybridization (FISH) wherever available. A total of 273 bone marrow aspirates and biopsies of patients with suspected plasma cell neoplasms were analyzed. There were 181 male patients and 92 female patients (Male: Female = 1.96: 1). There were 245 cases of multiple myeloma (89.7%), 8 cases of primary amyloidosis (2.9%) and 6 monoclonal gammopathy of undetermined significance (MGUS) (2.1%), 5 cases of plasmacytoma (1.8%) and 4 cases of smouldering myeloma (1.4%), 5 cases of POEMS syndrome (1.8%). Bone marrow fibrosis was noted in 12 patients at diagnosis (4.3%). Among the parameters studied, only the mean Hemoglobin was significantly low in patients with marrow fibrosis. Amyloid deposition in various organs including bone marrow, kidney, liver etc., were noted in 17 patients overall (6.2%). In conclusion, the incidence of fibrosis (4.3%) and amyloidosis (6.2%) associated with plasma cell neoplasms were much lower in our study as compared to published studies.

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Section: Discussionmentioning

confidence: 99%

Clinico-pathological profile of patients with plasma cell neoplasms with special reference to bone marrow fibrosis and amyloid deposition

Kannan,

Dass,

Dangudubiyyam

et al. 2023

J Clin Exp Hematopathol

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“…Thus, the assessment of BMF was concluded to have prognostic value in the follow-up of MM patients [ 13 ]. A recent study by Paul et al [ 14 ] showed that the median progression-free survival in patients without BMF was 30.2 months, while in those with BMF, it was 21 months. On the other hand, median OS was 61.2 months and 45.1 months among patients without and with BMF, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, median OS was 61.2 months and 45.1 months among patients without and with BMF, respectively. These findings were statistically significant [ 14 ]. Our results suggested that the pattern of plasma cell infiltration and the degree of fibrosis at diagnosis did not significantly influence survival times, possibly due to the relatively small groups in this study.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Bone Marrow Biopsy and Cytogenetic Findings in Patients with Multiple Myeloma

Seyhanli

Yavuz

Akşit

et al. 2021

Tjh

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Objective: Multiple myeloma (MM) is a malignant condition characterized by the accumulation of malignant plasma cells. Although MM remains incurable, the survival of MM patients has improved considerably due to the application of autologous stem cell transplantation, novel agents, and advanced treatment strategies. This study aimed to determine the cytogenetic characterization and bone marrow (BM) features of Turkish patients with MM. Materials and Methods: Eighty-five MM patients were admitted to Dokuz Eylül University Hospital in Turkey. BM samples of these MM patients were subjected to cytogenetic analyses at diagnosis and during therapy as a part of therapeutical and clinical evaluation. A complete cytogenetic study was performed using the G-banding technique. Fluorescence in situ hybridization (FISH) analysis was performed using cytoplasmic immunoglobulin. The degree of BM fibrosis was determined using reticulin histochemical staining. We determined the percentage of BM plasma cells based on the extent of CD38 staining. Results: Eighty-five MM patients were retrospectively identified between 2015 and 2021. The median age was 63 (38-90) years. Of the 85 patients, 60 (70.6%) were male and 25 (29.4%) were female. Seventy-two (84.7%) cases had BM fibrosis at the time of diagnosis. The most common was grade 2 fibrosis, recorded in 35 cases (41.2%). About 72.9% of the patients showed more than 50% plasma cells. FISH analysis indicated the presence of abnormal chromosomes in 37% (32/85) of the patients. The most frequent abnormality was Immunoglobulin heavy-chain (IGH) translocation (21.3%). Conclusion: Subgroup analysis of IGH mutations is crucial in the identification of high-risk MM patients. We believe that our study will contribute to the determination of BM biopsy and cytogenetic features of MM patients in our country.

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“…When the effects of BMF on MDS were investigated, it was found that overall survival and leukemia‐free survival were significantly shorter with an increase in BMF level 10 . Similarly, median progression‐free survival and median overall survival were found to be shorter in multiple myeloma patients with high BMF degree 11 . However, the effect of the degree of fibrosis in bone marrow biopsy on prognosis in DLBCL patients is not clear.…”

Section: Introductionmentioning

confidence: 99%

“…10 Similarly, median progression-free survival and median overall survival were found to be shorter in multiple myeloma patients with high BMF degree. 11 However, the effect of the degree of fibrosis in bone marrow biopsy on prognosis in DLBCL patients is not clear.…”

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confidence: 99%

Prognostic significance of bone marrow fibrosis in diffuse large B‐cell lymphoma

Cetintepe,

Ozkan,

Kucukzeybek

et al. 2024

Int J Lab Hematology

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IntroductionDiffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphomas. The aim of this study is to determine the relationship between the increase in the degree of fibrosis in the bone marrow and prognosis and mortality in newly diagnosed DLBCL.MethodsBone marrow biopsy of 153 newly diagnosed DLBCL patients was determined by staining with reticulin, Masson's trichrome histochemical stain, and the degree of fibrosis was determined.ResultsIn the bone marrow biopsy performed at the time of diagnosis, bone marrow fibrosis (BMF) was observed in 70 patients. While BMF‐1 was detected in 42 patients (60%), BMF‐2 was detected in 25 patients (35%) and BMF‐3 was detected in 3 patients (4%). As the degree of BMF increased, the median overall survival and median progression‐free survival times were significantly shorter (p: 0.008), (p < 0.001). In patients with an increased degree of BMF, a significant decrease in leukocyte and neutrophil counts was observed after chemotherapy (p: 0.004).According to the results of the multivariate Cox regression model, it was determined that high NCCN‐IPI risk (HR: 8.25; %95 CI: 1.09–62.52; p = 0.041) and being BMF ≥ 2 (HR: 3.75; %95 CI: 1.65–8.51; p = 0.002), increased the risk of death (p = 0.002, −2 loglikelihood = 392,553).ConclusionWhen the literature was reviewed, it was seen that this study was the first to define that bone marrow fibrosis grade 2 and above in DLBCL is a prognostic marker associated with worse survival. In the bone marrow pathology, which is examined to detect advanced disease in DLBCL, besides lymphomatous involvement, the detection of fibrosis grade is very important.

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The impact of bone marrow fibrosis and JAK2 expression on clinical outcomes in patients with newly diagnosed multiple myeloma treated with immunomodulatory agents and/or proteasome inhibitors

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 8 publications

References 40 publications

Clinico-pathological profile of patients with plasma cell neoplasms with special reference to bone marrow fibrosis and amyloid deposition

Clinico-pathological profile of patients with plasma cell neoplasms with special reference to bone marrow fibrosis and amyloid deposition

Assessment of Bone Marrow Biopsy and Cytogenetic Findings in Patients with Multiple Myeloma

Prognostic significance of bone marrow fibrosis in diffuse large B‐cell lymphoma

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