Combining information on C reactive protein and serum albumin into the Glasgow Prognostic Score strongly discriminates survival of myelofibrosis patients

Lucijanić, Marko; Cicic, David; Štoos‐Veić, Tajana; Pejša, Vlatko; Rahelić, Dario; Lucijanić, Tomo; Vasilj, Tamara; Ivić, Marija; Sedinić, Martina; Kušec, Rajko

doi:10.1016/j.bcmd.2018.06.001

Cited by 4 publications

(4 citation statements)

References 8 publications

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“…In turn, these cytokines are markedly decreased by treatment with ruxolitinib, while HSA levels are increased 15,16 . Recently, HSA level has been suggested as an independent indicator for prognosis in MF patients uncorrelated with cytogenetic or mutation profiles 17,18 . HSA and serum cholesterol levels were used to develop a new cachexia index further enhancing prognostication in MF 19 .…”

Section: Introductionmentioning

confidence: 99%

Ruxolitinib binding to human serum albumin: bioinformatics, biochemical and functional characterization in JAK2V617F+ cell models

Marinis

Ceccherelli

Quattrocchi

et al. 2019

Sci Rep

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Ruxolitinib is a type I JAK inhibitor approved by FDA for targeted therapy of Philadelphia-negative myeloproliferative neoplasms (MPNs), all characterized by mutations activating the JAK2/STAT signaling pathway. Treatment with ruxolitinib improves constitutional symptoms and splenomegaly. However, patients can become resistant to treatment and chronic therapy has only a mild effect on molecular/pathologic remissions. Drugs interaction with plasma proteins, i.e. human serum albumin (HSA), is an important factor affecting the intensity and duration of their pharmacological actions. Here, the ruxolitinib recognition by the fatty acid binding sites (FAs) 1, 6, 7, and 9 of HSA has been investigated from the bioinformatics, biochemical and/or biological viewpoints. Docking simulations indicate that ruxolitinib binds to multiple sites of HSA. Ruxolitinib binds to the FA1 and FA7 sites of HSA with high affinity (Kr = 3.1 μM and 4.6 μM, respectively, at pH 7.3 and 37.0 °C). Moreover, HSA selectively blocks, in a dose dependent manner, the cytotoxic activity of ruxolitinib in JAK2V617F+ cellular models for MPN, in vitro. Furthermore this event is accompanied by changes in the cell cycle, p27Kip1 and cyclin D3 levels, and JAK/STAT signaling. Given the high plasma concentration of HSA, ruxolitinib trapping may be relevant in vivo.

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Section: Introductionmentioning

confidence: 99%

Ruxolitinib binding to human serum albumin: bioinformatics, biochemical and functional characterization in JAK2V617F+ cell models

Marinis

Ceccherelli

Quattrocchi

et al. 2019

Sci Rep

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“…It is therefore of interest to combine them in the CAR or the GPS. For both parameters, a DIPSS-independent prognostic value has already been described in MF [10,11]. A recent report on acute myeloid leukemia patients not eligible for stem-cell transplantation illustrates that a combined assessment of CRP and albumin is of interest in myeloid malignancies in general [19].…”

Section: Discussionmentioning

confidence: 98%

“…Elevated CRP levels have been associated with several adverse disease features and a shorter leukemia-free survival [5,6], and albumin has been consistently shown to add additional prognostic information independently of DIPSS and several DIPSS-based prognostic scoring systems [7][8][9]. Furthermore, indices combining CRP and albumin such as the CRP/albumin ratio (CAR) [10] or the Glasgow Prognostic Score (GPS) [11] provide DIPSS-independent prognostic information in MF.…”

Section: Introductionmentioning

confidence: 99%

CRP/Albumin Ratio and Glasgow Prognostic Score Provide Prognostic Information in Myelofibrosis Independently of MIPSS70—A Retrospective Study

Messerich

Uda

Volken³

et al. 2023

Cancers

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In myelofibrosis, the C-reactive protein (CRP)/albumin ratio (CAR) and the Glasgow Prognostic Score (GPS) add prognostic information independently of the Dynamic International Prognostic Scoring System (DIPSS). Their prognostic impact, if molecular aberrations are considered, is currently unknown. We performed a retrospective chart review of 108 MF patients (prefibrotic MF n = 30; primary MF n = 56; secondary MF n = 22; median follow-up 42 months). In MF, both a CAR > 0.347 and a GPS > 0 were associated with a shorter median overall survival (21 [95% CI 0–62] vs. 80 months [95% CI 57–103], p < 0.001 and 32 [95% CI 1–63] vs. 89 months [95% CI 65–113], p < 0.001). Both parameters retained their prognostic value after inclusion into a bivariate Cox regression model together with the dichotomized Mutation-Enhanced International Prognostic Scoring System (MIPSS)-70: CAR > 0.374 HR 3.53 [95% CI 1.36–9.17], p = 0.0095 and GPS > 0 HR 4.63 [95% CI 1.76–12.1], p = 0.0019. An analysis of serum samples from an independent cohort revealed a correlation of CRP with levels of interleukin-1β and albumin with TNF-α, and demonstrated that CRP was correlated to the variant allele frequency of the driver mutation, but not albumin. Albumin and CRP as parameters readily available in clinical routine at low costs deserve further evaluation as prognostic markers in MF, ideally by analyzing data from prospective and multi-institutional registries. Since both albumin and CRP levels reflect different aspects of MF-associated inflammation and metabolic changes, our study further highlights that combining both parameters seems potentially useful to improve prognostication in MF.

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“…In the same study, increased RDW was associated with survival (p = 0.039). In MF, high CRP is associated with features of more advanced disease and a trend toward worse clinical outcomes as part of individual parameters or different prognostic scores [30][31][32] . In this study, no correlation was found between CRP and NLR and survival.…”

Section: Discussionmentioning

confidence: 99%

Systemic inflammatory indices for predicting prognosis of myelofibrosis

Ersal

Özkocaman

Pınar

et al. 2023

Sci Rep

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The impact of inflammatory markers such as systemic immune-inflammation (SII) index and systemic inflammation response index (SIRI) on myelofibrosis (MF) prognosis was evaluated for the first time in this study. Data from 60 patients diagnosed with MF between March 2011 and September 2022 were retrospectively analyzed. In addition to disease-related markers, the impact of SII and SIRI on prognosis was evaluated. In our study, the overall median survival (OS) was 64 months. OS was significantly shorter in patients older than 65 years, with high ferritin and lymphocyte levels, transfusion dependence at diagnosis, platelet count below 100 × 109/L, Hb level below 8 g/dl, and high risk according to the dynamic international prognostic scoring system (DIPSS)-Plus score. When these variables were included in the multivariate Cox regression model, it was found that being older than 65 years, having a high ferritin value, being at high risk according to the DIPSS-plus score and Hb values below 8 increased the risk of death. Platelet-to-lymphocyte ratio (PLR) and SII index were lower in patients with a fatal outcome. No statistically significant relationship was found between SIRI and mortality. The findings of this study showed that low PLR and high ferritin were associated with poor prognosis in MF. Elevated SII and SIRI, evaluated for the first time in patients with myelofibrosis, did not predict prognosis. Since non-inflammatory variables play a role in the pathogenesis of MF, bone marrow indicators and systemic inflammation indicators derived from hematologic parameters may not be accurate.

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Combining information on C reactive protein and serum albumin into the Glasgow Prognostic Score strongly discriminates survival of myelofibrosis patients

Cited by 4 publications

References 8 publications

Ruxolitinib binding to human serum albumin: bioinformatics, biochemical and functional characterization in JAK2V617F+ cell models

Ruxolitinib binding to human serum albumin: bioinformatics, biochemical and functional characterization in JAK2V617F+ cell models

CRP/Albumin Ratio and Glasgow Prognostic Score Provide Prognostic Information in Myelofibrosis Independently of MIPSS70—A Retrospective Study

Systemic inflammatory indices for predicting prognosis of myelofibrosis

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