Hyperlipidemia is a risk factor for osteonecrosis in children and young adults with acute lymphoblastic leukemia

Mogensen, Signe Sloth; Schmiegelow, Kjeld; Grell, Kathrine; Albertsen, Birgitte Klug; Wehner, Peder Skov; Kampmann, Peter; Frandsen, Thomas Leth

doi:10.3324/haematol.2016.160507

Cited by 47 publications

(62 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The extensive use of asparaginase in the NOPHO ALL2008 protocol may influence GC pharmacokinetics [43][44][45] and also aggravate hyperlipidemia, 44,46,47 which has been proposed to be a risk factor for ON. 17,48 Considering the high incidence of symptomatic ON, randomized interventions could be considered investigating possible steps for preventing ON by changes in both doses and timing of dexamethasone as well as asparaginase. This hypothesis is being tested in the NOPHO ALL2008 randomized trial using PEG-ASP every 2 weeks versus every 6 weeks (clinicaltrials.gov no.…”

Section: Discussionmentioning

confidence: 99%

Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

Mogensen

Harila‐Saari

Mäkitie

et al. 2018

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

Mogensen

Harila‐Saari

Mäkitie

et al. 2018

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pritchett et al 35 reported that the preemptive long-term use of statin drugs reduces the later development of ON in adults receiving steroids compared with published incidences of adults receiving highdose steroids. Mogensen et al 45 recently reported hyperlipidemia as a significant risk factor for the development of ON in children and adolescents with ALL, while Bhojwani et al 46 reported no association between very elevated triglycerides and the development of ON. Until now, no data on the safety and efficacy of statin use for prevention and/or treatment of early-stage ON in children with ALL have been available.…”

Section: Pharmacological Interventionsmentioning

confidence: 99%

Osteonecrosis in children and adolescents with acute lymphoblastic leukemia: a therapeutic challenge

et al. 2017

View full text Add to dashboard Cite

Osteonecrosis (ON) represents one of the most common and debilitating sequelae of antileukemic treatment in children and adolescents with acute lymphoblastic leukemia (ALL). Systematic screening strategies can focus on early detection and intervention to prevent ON from progressing to stages associated with pain and functional impairment.These strategies hold promise for reducing ON-associated morbidity without the risk of impairing leukemia control. Herein, we critically reviewed clinical data on pharmacological, nonpharmacological/nonsurgical, and surgical (including cellular) treatment options for ON, which are covered in the literature and/or are conceivable based on the supposed underlying ON pathophysiology. Prevention of ON progression is of paramount importance, and attempts seem to be more effective in early (precollapse) disease status than in late-stage (collapse) ON. Based on the results of ongoing prospective magnetic resonance imaging screening studies, which will hopefully identify those patients with a high risk of ON progression and debilitating sequelae, prospective interventional studies are urgently needed. Although there is still a lack of high-quality studies, based on currently available data, core decompression surgery combined with cellular therapies (eg, employing mesenchymal stem cells) appears most promising for preventing joint infraction in children at high risk of developing late-stage ON.

show abstract

“…The association between hypertriglyceridemia and other toxicities (thrombosis, osteonecrosis, and pancreatitis) has been previously studied. 6,[14][15][16][17] It has been suggested that hypertriglyceridemia may be associated with osteonecrosis and thrombosis, although the associations were not maintained in multivariate analyses. 6 However, there are few large-scale studies to support hypertriglyceridemia as an independent risk factor.…”

Section: Introductionmentioning

confidence: 99%

Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia

Finch

Smith

Yang

et al. 2019

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Background Glucocorticoids and asparaginase, used to treat acute lymphoblastic leukemia (ALL), can cause hypertriglyceridemia. We compared triglyceride levels, risk factors, and associated toxicities in two ALL trials at St. Jude Children's Research Hospital with identical glucocorticoid regimens, but different asparaginase formulations. In Total XV (TXV), native Escherichia coli l‐asparaginase was front‐line therapy versus the pegylated formulation (PEG‐asparaginase) in Total XVI (TXVI). Procedure Patients enrolled on TXV (n = 498) and TXVI (n = 598) were assigned to low‐risk (LR) or standard/high‐risk (SHR) treatment arms (ClinicalTrials.gov identifiers: NCT00137111 and NCT00549848). Triglycerides were measured four times and were evaluable in 925 patients (TXV: n = 362; TXVI: n = 563). The genetic contribution was assessed using a triglyceride polygenic risk score (triglyceride‐PRS). Osteonecrosis, thrombosis, and pancreatitis were prospectively graded. Results The largest increase in triglycerides occurred in TXVI SHR patients treated with dexamethasone and PEG‐asparaginase (4.5‐fold increase; P <1 × 10−15). SHR patients treated with PEG‐asparaginase (TXVI) had more severe hypertriglyceridemia (>1000 mg/dL) compared to native l‐asparaginase (TXV): 10.5% versus 5.5%, respectively (P = .007). At week 7, triglycerides did not increase with dexamethasone treatment alone (LR patients) but did increase with dexamethasone plus asparaginase (SHR patients). The variability in triglycerides explained by the triglyceride‐PRS was highest at baseline and declined with therapy. Hypertriglyceridemia was associated with osteonecrosis (P = .0006) and thrombosis (P = .005), but not pancreatitis (P = .4). Conclusion Triglycerides were affected more by PEG‐asparaginase than native l‐asparaginase, by asparaginase more than dexamethasone, and by drug effects more than genetics. It is not clear whether triglycerides contribute to thrombosis and osteonecrosis or are biomarkers of the toxicities.

show abstract

Hyperlipidemia is a risk factor for osteonecrosis in children and young adults with acute lymphoblastic leukemia

Cited by 47 publications

References 14 publications

Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia

Osteonecrosis in children and adolescents with acute lymphoblastic leukemia: a therapeutic challenge

Asparaginase formulation impacts hypertriglyceridemia during therapy for acute lymphoblastic leukemia

Contact Info

Product

Resources

About