Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia

Abstract

As survival of acute lymphoblastic leukemia (ALL) exceeds 90%, limiting therapy-related toxicity has become a key challenge. Cardio-metabolic dysfunction is a challenge during and after childhood ALL therapy. In a single center study, we measured triglycerides (TG), total cholesterol (TC), high (HDL) and low density lipoproteins (LDL) levels at diagnosis and assessed the association with BMI, early therapy response, on-therapy hyperlipidemia and the toxicities; thromboembolism, osteonecrosis and pancreatitis. We included 127 children (1.0-17.9 years) all treated according to the NOPHO ALL2008 protocol. Dyslipidemia was identified at ALL-diagnosis in 99% of the patients, dominated by reduced HDL levels (98%) and mild hypertriglyceridemia (61%). Hypertriglyceridemia was not associated with body mass index (P = 0.71). Five percent of patients had mild hypercholesterolemia, 14% had mild hypocholesterolemia, 13% had decreased and 1% elevated LDL-levels. Increased TG and TC levels at ALL-diagnosis were not associated with any on-therapy lipid levels. Lipid levels and BMI were not associated to MRD after induction therapy; However, BMI and hypercholesterolemia were associated with worse risk group stratification (P<0.045 for all). The cumulative incidence of thromboembolism was increased both for patients with hypo-(20.0%) and hypercholesterolemia (16.7%) compared to patients with normal TC levels (2.2%) at diagnosis (P = 0.0074). In conclusion, dyslipidemic changes were present prior to ALL-therapy in children with ALL but did not seem to affect dysmetabolic traits during therapy and were not predictive of on-therapy toxicities apart from an association between dyscholesterolemia at time of ALL-diagnosis and risk of thromboembolism. However, the latter should be interpreted with caution due to low number in the groups.

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells

“…Even without obesity, children with ALL have metabolic derangements that increase lipid availability. In one cohort, 99% of children with newly diagnosed ALL had dyslipidemia, with most exhibiting hypertriglyceridemia, irrespective of BMI (52). Current ALL chemotherapy regimens, specifically those c o n t a i n i n g L -a s p a r a g i n a s e , a r e k n o w n t o c a u s e hypertriglyceridemia and hypercholesterolemia (53,54).…”

SOHO State of the Art Updates and Next Questions: Management of Asparaginase Toxicity in Adolescents and Young Adults with Acute Lymphoblastic Leukemia

“…Apart from Asp therapy and older age, established risk factors for AAP are few 6,113 . Thus, neither corticosteroid-and Asp-induced hypertriglyceridemia 37,73,[81][82][83][114][115][116][117] or high body mass index have been confirmed as risk factors 118,119 . Although several SNPs have been found to be associated with alcoholic or familial pancreatitis, only rs13228878 and rs10273639 have been validated in a childhood ALL setting leading to elevated expression of the gene PRSS1 encoding for trypsinogen 110 .…”

“…Additional risk factors include concurrent infections, non-O blood group, physical inactivity, obesity, and use of oral contraceptives, whereas the impact of corticosteroid-and Asp-induced hypertriglyceridemia remains unclear [81][82][83] .…”

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

“…Hypocholesterolaemia, possibly due to increased demand and uptake of cholesterol esters, has been reported in patients with lung [ 12 , 13 ], gastrointestinal [ 14 ], thyroid [ 15 ], breast [ 16 ], ovarian [ 17 ], and prostate [ 18 ] cancers. In addition to solid tumours, decreased cholesterol levels have also been observed in haematological cancers [ 19 ], such as CLL [ 20 ], acute lymphocytic leukaemia [ 21 ], lymphomas [ 22 ], and multiple myeloma [ 23 ]. However, the prognostic significance of hypocholesterolaemia in these malignancies is less investigated.…”