Low Serum Cholesterol Level Is a Significant Prognostic Factor That Improves CLL-IPI in Chronic Lymphocytic Leukaemia

Abstract

Hypocholesterolaemia is associated with elevated cancer risk and mortality, yet the relation between chronic lymphocytic leukaemia (CLL) and serum lipid profile remains unclear. Our study aims to evaluate the prognostic value of cholesterol levels in CLL and develop a prognostic nomogram that incorporates lipid metabolism. We enrolled 761 newly diagnosed CLL patients and separated them into either derivation (n = 507) or validation (n = 254) cohorts. The prognostic nomogram was constructed through multivariate Cox regression analyses, with performance evaluated using C-index, the area under the curve, calibration, and decision curve analyses. Decreased total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) at diagnosis were significantly associated with worse time to first treatment (TTFT) and cancer-specific survival (CSS), and simultaneously, low HDL-C with low LDL-C was identified as an independent prognostic indicator for both TTFT and CSS. CLL patients achieving complete or partial remission post-chemotherapy had significantly increased TC, HDL-C, and LDL-C levels compared with the baseline, and post-therapeutic HDL-C and LDL-C elevation correlated with favourable survival. The prognostic nomogram augmenting the CLL international prognostic index with low cholesterol levels yielded higher predictive accuracy and discrimination capacity for both 3-year and 5-year CSS. In conclusion, cholesterol profiles can be used as a cheap and readily accessible tool for predicting prognosis in CLL practice.

Low serum total cholesterol levels predict inferior prognosis of patients with POEMS syndrome

“…Kuliszkiewicz-Janus et al discovered a simultaneous reduction in TC, HDL-C and LDL-C concentrations during disease activity of acute leukemia and non-Hodgkin's lymphoma (NHL) [ 21 ]. Gao et al identified the lipid profiles in CLL and diffuse large B-cell lymphoma (DLBCL), which manifested as reduced concentrations of TC, HDL-C and LDL-C [ 10 , 13 ]. Yavasoglu et al also discovered that newly diagnosed CLL and multiple myeloma (MM) patients had significantly lower TC, HDL-C and LDL-C levels [ 9 , 14 ].…”

“…In DLBCL patients, Gao et al showed that TC was linked to poor PFS and OS [ 13 ]. Additionally, CLL patients with hypocholesterolemia also had a worse time to first treatment (TTFT) and cancer-specific survival (CSS) [ 10 ]. Serum cholesterol has therefore been proposed as a prognostic indicator for POEMS syndrome.…”

“…Hypocholesterolemia has been found in patients with lung [ 5 ], gastrointestinal [ 6 ] and thyroid [ 7 ] cancers. Decreased cholesterol levels have been found in patients with hematological tumors [ 8 ], which is consistent with solid tumors such as chronic lymphocytic leukemia (CLL) [ 9 , 10 ], acute lymphocytic leukemia [ 11 ], lymphoma [ 12 , 13 ], and multiple myeloma [ 14 ], which may be due to increased use of cholesterol as an energy source by tumor cells. Cholesterol production, accumulation, demand and absorption were found to be increased in neoplastic cells, and this was particularly true for hematological tumors, which had a comparatively faster cell renewal rate than solid tumors.…”

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

“…Hypocholesterolemia has been reported in oncohematological disorders. Decreased levels of total cholesterol, HDL-C, and LDL-C were observed in patients with multiple myeloma [ 68 ], lymphoma [ 69 ], and, most recently, in patients with newly diagnosed CLL [ 70 ]. One study [ 67 ] developed a prognostic nomogram including these analytical parameters at the time of diagnosis as a significant predictive predictor.…”

The Role of Cholesterol in Chronic Lymphocytic Leukemia Development and Pathogenesis

“…Another study reported lower serum levels in CLL patients compared to healthy individuals, with CLL patients averaging 151.2 +/− 11.2 mg/dL compared to 195.3 +/− 8.5 mg/dL in healthy, aged-matched controls [ 17 ]. CLL patients with hypocholesterolemia have a shorter overall and treatment-free survival [ 18 ], possibly due to increased catabolism of LDL and impaired hepatic lipoprotein synthesis [ 17 ], or increased expression of the LDL receptor (LDLR) on CLL cells [ 19 ], leading to increased cellular uptake.…”