Central Venous Lines in Children With Lesser Risk Acute Lymphoblastic Leukemia: Optimal Type and Timing of Placement

2005 ◽  
Vol 23 (13) ◽  
pp. 3024-3029 ◽  
Author(s):  
Thomas W. McLean ◽  
Christen J. Fisher ◽  
Beverly M. Snively ◽  
Allen R. Chauvenet
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Blood Culture ◽  
Positive Blood Culture ◽  
Odds Ratio ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Complication Rates ◽  
Central Venous ◽  
Increased Risk ◽  
Optimal Type

Purpose In pediatric patients with acute lymphoblastic leukemia (ALL), the optimal time for central venous line (CVL) insertion and the optimal type of CVL (internal v external) is unclear. This study was undertaken to compare complication rates between early versus late line insertion, and between internal versus external lines in children with lesser risk ALL. Patients and Methods We performed a retrospective analysis of patients enrolled onto Pediatric Oncology Group (POG) protocol 9201. Data regarding demographics, CVL types and insertion dates, blood counts, and complications were reviewed through week 25 of therapy. Results Of 697 patients enrolled onto POG protocol 9201, 362 patients had sufficient data for analysis. When compared to late line placement (> day 15 of induction), early CVL placement (≤ day 15 of induction) was associated with an increased risk of having a positive blood culture (odds ratio, 2.2; 95% CI, 1.0 to 5.0; P = .05). When compared with internal CVLs (“ports”), external CVLs were associated with a positive blood culture (odds ratio, 3.1; 95% CI, 1.3 to 7.5; P = .01), thrombosis (odds ratio, 3.9; 95% CI, 1.5 to 10.3; P = .006), and CVL removal (odds ratio, 5.6; 95% CI, 2.7 to 11.6; P < .001). Conclusion In pediatric patients with lesser risk ALL, internal lines (ports) should be the preferred CVL type due to a lower risk of infectious and thrombotic complications. In addition, CVLs placed early in induction are associated with a higher risk of positive blood culture than those placed later in induction.

Validation of a Predictive Model for Indentifying An Increased Risk for Thromboembolism in Children with Acute Lymphoblastic Leukemia: Results of a Multicenter Cohort Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 524-524
Author(s):  
Silke Flege ◽  
Lesley Mitchell ◽  
Gili Kenet ◽  
Christine Heller ◽  
Michael Fruhwald ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Predictive Model ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Low Risk ◽  
Carrier Status ◽  
Central Venous ◽  
Increased Risk ◽  
Genetic Abnormalities

Abstract Children with acute lymphoblastic leukemia (ALL) are at increased risk for venous thromboembolism (VTE), however, not all children experience a VTE. Developing a predictive model for determining children at increased risk would be beneficial in targeting interventional studies to only high risk groups. A recent meta-analysis of studies in VTE in children with ALL identified four potential risk factors: treatment with Escherichia coli asparaginase (CASP), concomitant use of steroids, presence of central venous lines and thrombophilic genetic abnormalities. As VTE in childhood ALL is well recognized as serious clinical problem and due to the lack of studies on prevention, the standard of practice varies and some centres use enoxaparin prophylaxis for these children. However, the risks and benefits of the intervention are unknown. The aim of the study was to develop a simple model for predicting ALL-chemotherapy-associated VTE using baseline clinical and laboratory variables, and to evaluate, on an explorative basis, the increasing off-label use of enoxaparin for VTE prophylaxis in ALL children. For development of the risk model the predictive variables were scored as follows: treatment with CASP (5000–10000/m2) in combination with prednisone or dexamethasone, presence of central venous lines, thrombophilic genetic abnormalities, e.g. positive family history for VTE or identification of a single thrombophilic trait (1 point each), or carrier status of combined thrombophilic traits (2 points). A definition of VTE risk by score was low (1–2) and high (□ 3). The risk score was than prospectively validated in an independent cohort of 136 newly recruited patients enrolled into the German database. Seven patients were excluded (lost to follow-up n=2; death n=2, secondary malignancy, VTE before ALL-onset, infant &lt; 12 months of age: each n=1). The cumulative VTE rates at 3.5 months in the validation cohorts were 3.6% (95% CI 1%–9%) in the low-risk group (4 of 112), and 47% (95%CI 23%–72%) in the high-risk category (8 of 17). In multivariate analysis [Cox regression] the high risk group was significantly associated with VTE when compared to the low risk group even after adjusting for age at ALL-onset, duration of CASP administration, steroid administered (prednisone/dexamethasone), and presence or absence of enoxaparin prophylaxis [hazard/95%CI: 4.16/1.13–15.34]. The negative predictive value for VTE was 96.3% [95%CI: 92.9–99.8]. Early enoxaparin prophylaxis reduced the absolute VTE-risk about 60% [95%CI: 23–96]. Therefore, the model can identify ALL-children with an increased risk for symptomatic VTE.

Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Determinants of Osteonecrosis In Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1033-1033
Author(s):  
Jitesh D. Kawedia ◽  
Sue Kaste ◽  
Deqing Pei ◽  
John C Panetta ◽  
Xiangjun Cai ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Serum Albumin ◽  
Serum Cholesterol ◽  
Odds Ratio ◽  
Lymphoblastic Leukemia ◽  
Elevated Serum ◽  
Systemic Exposure ◽  
Genomic Variation ◽  
Cholesterol Levels ◽  
Increased Risk

Abstract Abstract 1033 Osteonecrosis is a debilitating corticosteroid-induced toxicity in patients treated for acute lymphoblastic leukemia (ALL). Our goal was to ascertain genetic and non-genetic risk factors for this complication. In St. Jude Total XV protocol for children with newly diagnosed ALL, we prospectively screened 365 patients with magnetic resonance imaging of hips and knees, irrespective of symptoms. We determined whether age, race, sex, ALL treatment arm, body mass index, serum lipids, albumin and cortisol levels, dexamethasone pharmacokinetics and genome-wide germline genetic polymorphisms were associated with symptomatic (grade 2–4) osteonecrosis. Sixty-eight patients developed symptomatic osteonecrosis with a cumulative incidence of 17%. Age greater than 10 years (odds ratio 4.8; 95 % confidence interval [CI], 2.5–9.2; p = 0.00001) and treatment arm (standard/high risk vs. low risk) (odds ratio 2.5; 95% CI 1.2–4.9; p = 0.011) were associated with increased risk of osteonecrosis, and were included as covariates in all other analyses. Lower serum albumin (p = 0.04) and higher serum cholesterol levels (p = 0.02) were associated with symptomatic (grade 2–4) osteonecrosis. In addition, higher dexamethasone plasma exposure (area-under-the-curve) was associated with severe (grade 3–4) osteonecrosis (p = 0.0007). After adjusting for clinical features (age and treatment arm), we identified several single nucleotide polymorphisms (SNPs) associated with the risk of developing osteonecrosis. These include: ACP1 (rs12714403, p = 1.03 × 10-5; odds ratio 4.8; 95% CI 2.4–9.6), a gene involved in regulation of lipids and osteoblast differentiation; and SH3YL1 (rs4241316, p = 5.7 × 10-6; odds ratio 5.0; 95% CI 2.5–10.1). These SNPs were also associated with lower albumin and elevated serum cholesterol levels. In conclusion, older age, lower albumin levels, increased dexamethasone systemic exposure, and higher cholesterol levels were associated with osteonecrosis. Inherited genomic variation that predisposes to osteonecrosis may do so via pleiotropic effects on dexamethasone pharmacokinetics, serum cholesterol and serum albumin. Disclosures: Pui: EUSA Pharma: Honoraria; Enzon: Honoraria; Sanofi-Aventis: Honoraria. Relling:St. Jude Children's Research Hospital: Employment, Patents & Royalties; Enzon Pharmaceuticals: Research Funding.

A SERPINE1 (PAI-1) Single Nucleotide Polymorphism Predicts Osteonecrosis in Children Treated for Acute Lymphoblastic Leukemia: Results of the Children’s Oncology Group (COG) Study AALL03B2.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 709-709
Author(s):  
Leo H. Hamilton ◽  
Leonard A. Mattano ◽  
Harland N. Sather ◽  
Mary V. Relling
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Lymphoblastic Leukemia ◽  
Odds Ratio ◽  
Lymphoblastic Leukemia ◽  
Plasminogen Activator Inhibitor ◽  
Serum Levels ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Pai 1

Abstract As intensity of glucocorticoid use has increased, osteonecrosis has become an increasingly frequent complication of modern intensive chemotherapy for pediatric patients with acute lymphoblastic leukemia (ALL). Although patient age &gt; 10 years is a well-known risk factor, other host risk factors that may predispose to this complication are not well described. We tested whether 12 polymorphisms in 11 candidate genes were associated with osteonecrosis among up to 344 patients ≥ 10 years old treated on the Children’s Cancer Group protocol CCG 1882 for newly diagnosed high-risk ALL, adjusting for gender, age, and treatment arm (augmented versus standard treatment). Genes tested (TYMS, ER, MTHFR, ABCB1, BGLAP (osteocalcin), ACP5, LRP5, ESR, SERPINE1, VDR, PTH, and PTHR) were chosen because they are candidates based on the putative mechanisms underlying osteonecrosis risk, including involvement in antifolate pharmacodynamics, drug pharmacokinetics, thrombosis risk, and possible hormonal influence on glucocorticoid effects. All children received dexamethasone during the delayed intensification phase of therapy, with doses varying by treatment arm (one dexamethasone pulse in the standard chemotherapy arm vs. two dexamethasone pulses in the augmented chemotherapy arm). Of the 11 candidate polymorphisms, a single nucleotide polymorphism (dbSNP rs6092) in the SERPINE1 gene (plasminogen activator inhibitor type 1 or PAI-1) was the only polymorphism associated with an increased risk of osteonecrosis in both univariate (p=0.0039) and multivariate (p=0.0019) analyses (adjusting for gender, age, and treatment arm), with an odds ratio of 2.51 (95% CI 1.32 to 4.74). Overall, 23.9% of the 88 children heterozygous or homozygous for the SERPINE1 T allele, versus 11.1% of the 234 children homozygous for the C allele, developed osteonecrosis. The combined CT or TT genotypes were present in a greater percentage (27%) of whites than in blacks (12%, p = 0.016), consistent with a higher risk (p = 0.003) of osteonecrosis in whites than blacks that was originally reported for CCG-1882 (J Clin Oncol18:3262–72, 2000). In a multivariate analysis, only the SERPINE1 polymorphism and sex predicted AVN, with the incidence of osteonecrosis lower in boys (odds ratio 0.49, 95% confidence interval 0.25 to 0.96, p = 0.034). No statistically significant gene-gene interactions between SERPINE1 and any other tested genotype were noted. SERPINE1 polymorphisms and PAI-1 serum levels have previously been associated with a clinical pro-thrombotic state. We conclude that polymorphisms in SERPINE1 may contribute to the risk of osteonecrosis in patients treated with glucocorticoids.

Gut bacterial gene changes following pegaspargase treatment in pediatric patients with acute lymphoblastic leukemia

2021 ◽  
pp. 1-12
Author(s):  
Katherine A. Dunn ◽  
Zara Forbrigger ◽  
Jessica Connors ◽  
Mushfiqur Rahman ◽  
Alejandro Cohen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Bacterial Gene

Screening for asymptomatic diabetes and metabolic comorbidities in pediatric patients during therapy for acute lymphoblastic leukemia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Valerie Larouche ◽  
Caroline Bellavance ◽  
Pauline Tibout ◽  
Sebastien Bergeron ◽  
David Simonyan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Fasting Blood Glucose ◽  
Metabolic Disturbances ◽  
Metabolic Complications ◽  
Glucose Levels ◽  
Oncology Unit ◽  
Hba1c Levels

Abstract Objectives Chronic metabolic disturbances related to cancer treatment are well reported among survivors of pediatric acute lymphoblastic leukemia (ALL). However, few studies have investigated the incidence of these complications during the phase of chemotherapy. We evaluated the incidence of acute metabolic complications occurring during therapy in our cohort of patients diagnosed with ALL. Methods A prospective study involving 50 ALL pediatric patients diagnosed and treated between 2012 and 2016 in our oncology unit. We collected weight, blood pressure, fasting plasma glucose and hemoglobin A1C (HBA1c) levels during the two years of therapy. Results Obesity and overweight occurred in 43 and 25%, respectively among patients and have been reached at 12 months of chemotherapy. About 26% of the patients developed high blood pressure and 14% experienced hyperglycemias without meeting diabetes criteria. There was a significant decrease of HBA1c levels between the beginning and the end of therapy (p<0.0001). Conclusions Increase of body mass index in our ALL pediatric patients occurred during the first months of therapy and plateaued after a year of treatment. We should target this population for early obesity prevention. HbA1c levels measured during therapy did not reveal diabetes criteria. Hence, fasting blood glucose levels are sufficient to monitor ALL pediatric patients’ glycemia.

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