Development of a prognostically relevant cachexia index in primary myelofibrosis using serum albumin and cholesterol levels

Tefferi, Ayalew; Nicolosi, Maura; Penna, Domenico; Mudireddy, Mythri; Szuber, Natasha; Lasho, Terra L.; Hanson, Curtis A.; Ketterling, Rhett P.; Gangat, Naseema; Pardanani, Animesh

doi:10.1182/bloodadvances.2018018051

Cited by 18 publications

(15 citation statements)

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“…Detection of unexpected hypertriglyceridemia with hypocholesterolemia may bring into question the above-mentioned pathologies and, in the absence of these pathologies, the possibility of chronic disease or malignancy should be investigated. It was stated that dyslipidemia can be used as a prognostic marker in some hematological neoplasms 21 . Therefore, it may be necessary to determine different cut-off values for triglyceride, total cholesterol, LDL, and HDL so as to use them as diagnostic or prognostic markers in patients with a malignancy.…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between Hematological Neoplasms and Lipid Profile

Öztürk¹

2021

MMJ

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Objective: Hypocholesterolemia is a metabolism disorder that may be seen in chronic diseases and malignancies. Various dyslipidemia profiles have been shown in adult and pediatric hematological malignancies. We aimed to evaluate the lipid profile properties in patients diagnosed with a hematological malignancy compared to a healthy control group. Method: Out of 1213 patients diagnosed with hematologic malignancy, the data of 98 patients whose pretreatment lipid profiles had already been studied, were reviewed. Forty healthy individuals were selected as the control group. The levels of total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were compared. Results: Triglyceride values were significantly higher (p=0.02), and the total cholesterol, LDL and HDL levels were lower in the study group compared to the control group. Triglyceride values were higher (p=0.013), and HDL levels were lower (p=0.022) in parallel with increases in uric acid levels. There was a significant correlation between the International Prognostic Index (IPI) score and TG (p=0.003) in those diagnosed with non-Hodgkin lymphoma (NHL). Whereas no significant correlation was found between TG, total cholesterol, and LDL values in the limited (early) and advanced stage NHL, while a significant negative correlation was found with HDL (p=0.027). Conclusion: Hypertriglyceridemia, as well as low LDL and HDL values may be seen in hematological malignancies. It should be kept in mind that there may be chronic diseases and malignancies in the etiology of incidental hypocholesterolemia and hypertriglyceridemia. Further studies are needed on this subject to determine the effects of dyslipidemia on the pathogenesis and prognosis of the disease in hematological malignancies.

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Section: Discussionmentioning

confidence: 99%

The Relationship Between Hematological Neoplasms and Lipid Profile

Öztürk¹

2021

MMJ

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“…Cachexia is a multifactorial syndrome, with several triggering causes including low nutritional intake due to bothersome splenomegaly [ 84 ], which might be a plausible explanation of the high level of “early satiety” reported by the underweight MPN patients in the present study. Besides splenomegaly, it is currently assumed that both the metabolic disturbances and the constitutional symptoms in MF, at least partly, are a result of a cytokine-driven systemic inflammatory state induced by the dysregulation of the JAK-STAT pathway [ 84 , 86 ]. The JAK-STAT pathway is vital in the regulation of pro-inflammatory cytokines such as IL-6 and TNF-α of which both have been shown to be involved in the modulation of cachexia [ 84 , 87 ].…”

Section: Discussionmentioning

confidence: 99%

Body Mass Index and Total Symptom Burden in Myeloproliferative Neoplasms Discovery of a U-shaped Association

Christensen

Scherber

Brochmann

et al. 2020

Cancers

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Elevated body mass index (BMI) is a global health problem, leading to enhanced mortality and the increased risk of several cancers including essential thrombocythemia (ET), a subtype of the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). Furthermore, evidence states that BMI is associated with the severity of symptom burden among cancer patients. MPN patients often suffer from severe symptom burden. The purpose of this study was to examine whether deviations from a normal BMI in an MPN population are associated with higher symptom burden and reduced quality of life (QoL). A combined analysis of two large cross-sectional surveys, the Danish Population-based Study, MPNhealthSurvey (n = 2044), and the international Fatigue Study (n = 1070), was performed. Symptoms and QoL were assessed using the validated Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF). Analysis of covariance was used to estimate the effects of different BMI categories on symptom scores while adjusting for age, sex, and MPN subtype. A U-shaped association between BMI and Total Symptom Burden was observed in both datasets with significantly higher mean scores for underweight and obese patients relative to normal weight (mean difference: underweight 5.51 (25.8%), p = 0.006; obese 5.70 (26.6%) p < 0.001). This is an important finding, as BMI is a potentially modifiable factor in the care of MPN patients.

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“…At the same time, it is reasonable to question added value, in the context of a more comprehensive risk model, such as MIPSS70+ version 2.0 . In this regard, the possible prognostic interaction with constitutional symptoms requires a prospective evaluation, including analysis of the recently unveiled cachexia index for PMF . Whether or not the JAK2 46/1 haplotype influences survival or thrombosis risk in other MPN, or for that matter in the general population, remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

The germline JAK2 GGCC (46/1) haplotype and survival among 414 molecularly‐annotated patients with primary myelofibrosis

et al. 2018

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JAK2 mutations in myeloproliferative neoplasms (MPNs) are associated with the germline GGCC (46/1) haplotype. In 2010, we reported an association between shortened survival in primary myelofibrosis (PMF) and nullizygosity for the JAK2 46/1 haplotype. In the current study, we have increased the number of informative cases from 130 to 414 (median age 63 years; 63% males), in order to revisit with the phenotypic and prognostic relevance of the JAK2 46/1 haplotype in PMF. JAK2 46/1 haplotype was documented in 69% of the study patients, including 25% in homozygous and 44% in heterozygous state. Driver mutation frequency in patients homozygous/heterozygous/nullizygous for the 46/1 haplotype was 78%/60%/56% JAK2, 10%/20%/18% type 1‐like CALR, 3%/2%/5% type 2‐like CALR, 4%/8%/7% MPL, and 6%/10%/14% triple‐negative (P = .02). In univariate analysis, nullizygosity for the JAK2 46/1 haplotype was associated with inferior overall survival (HR 1.5, 95% CI 1.1‐1.9), most pronounced in JAK2 (P <.001), as opposed to CALR/MPL mutated (P = .48) or triple‐negative cases (P = .27). Multivariable analysis that included karyotype, driver mutational status and high‐molecular risk mutations confirmed the independent prognostic contribution of nullizygosity for the 46/1 haplotype (P = .02; HR 1.4, 95% CI 1.1‐1.8). Nullizygosity for 46/1 also remained significant in the context of the genetically‐inspired GIPSS risk model (P = .04), but not in the context of the integrated genetics‐clinical MIPSS70+ version 2.0 model (P = .4). Leukemia‐free survival was not affected by the 46/1 haplotype (P = .6). The current study confirms the association of nullizygosity for the JAK2 GGCC (46/1) haplotype with inferior survival in JAK2‐mutated PMF.

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Development of a prognostically relevant cachexia index in primary myelofibrosis using serum albumin and cholesterol levels

Abstract: Key Points Serum albumin and cholesterol levels predict survival in primary myelofibrosis, independent of each other and contemporary risk models. The cachexia index, determined by serum albumin and cholesterol levels, might further refine current prognostic models in myelofibrosis.

Cited by 18 publications

References 18 publications

The Relationship Between Hematological Neoplasms and Lipid Profile

The Relationship Between Hematological Neoplasms and Lipid Profile

Body Mass Index and Total Symptom Burden in Myeloproliferative Neoplasms Discovery of a U-shaped Association

The germline JAK2 GGCC (46/1) haplotype and survival among 414 molecularly‐annotated patients with primary myelofibrosis

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