scholarly journals Mediastinal Mass, Triglycerides Level Above 1000mg/Dl and Intensive Dexamethasone and Asparaginase Treatment Are Risk Factors for Cerebral Sinus Venous Thrombosis in Children Treated for Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5163-5163
Author(s):  
Habib El-Khoury ◽  
Khaled M Ghanem ◽  
Yaacoub Mubarak ◽  
Nidale Tarek ◽  
Hassan El Solh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia ◽  
Significant Risk ◽  
Cancer Center ◽  
Group I ◽  
Increased Risk ◽  
Cerebral Sinus Venous Thrombosis ◽  
Risk Patients

Abstract Background: Cerebral sinus venous thrombosis (CSVT) is a serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No universal consensus exists regarding its risk factors due to rarity of cases. The effect of CSVT on outcome is not limited to its own complications but extends to its possible negative impact on ALL therapy. Age above 10 years, T-cell immunophenotype and risk stratification (intermediate/high risk) were previously shown to be statistically significant risk factors for CSVT in our cohort of patients with an odds ratio of 3.56, 2.32 and 3.40 respectively and a P-Value of 0.03, 0.02 and 0.04 respectively (Ghanem et al. 2017). Aims and Methods: This is a prospective study of a pediatric cohort of children between 1 and 18 years of age treated for Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon (CCCL) between 2007 and 2017 with a protocol adopted from St Jude TOT XV. The aim of this analysis is to study the effect of decreasing asparginase and dexamethasone doses on the incidence of CSVT in addition to studying the effect of the following potential risk factors: presence of mediastinal mass at diagnosis, triglycerides level above 1000mg/dL and elevated initial blast count. In 2015, L-asparginase doses were decreased during induction from 10,000IU/m2/dose to 6,000IU/m2/dose and Dexamethasone doses were decreased from 12mg/m2/dose to 8mg/m2/dose for intermediate/high risk patients and from 8mg/m2/dose to 6mg/m2/dose for low risk patients. Patients were divided into two groups: group I for individuals treated between 2007 and 2015 and group I for individuals treated between 2015 and 2017. Results: A total of 202 patients were recruited (Group I, N=126 and Group II, N=76). The incidence of CSVT was 10.3% in group I and 1.3 % in group II. Univariate analysis showed that, treatment with intensive dexamethasone and asparginase in group I was a significant risk factor for CSVT (OR: 9.3, 95% CI: 1.2 - 72, P=0.03). Initial mediastinal mass (OR: 19.3, 95% CI: 5.4 - 68.6, P<0.0001) and triglycerides level above 1000mg/dL (OR: 3.4, 95% CI: 0.98 - 12, P=0.05) were also associated with increased risk of CSVT. Initial peripheral blast count ≥10,000 (OR: 0.57, 95% CI: 0.19 - 1.7, P=0.31), ≥50,000 (OR: 0.7, 95% CI: 0.14-3.35, P=0.66), and ≥100,000 (OR: 1.53, 95% CI: 0.29-7.82, P=0.61) were not risk factors for CSVT in our cohort. Conclusion: Decreasing the doses of dexamethasone and asparginase significantly lowered the risk of CSVT in our patient population. Initial mediatinal mass and triglycerides levels above 1000mg/dL during asaparginase therapy were significantly associated with increased risk of developing CSVT. If future studies confirm our findings, mediastinal mass and elevated triglycerides level may be considered amongst other factors predisposing to CSVT and may help identify candidates for thromboprophylaxis in the future. Disclosures No relevant conflicts of interest to declare.

scholarly journals Treatment Induced Cerebral Sinus Venous Thrombosis in Childhood Acute Lymphoblastic Leukemia: New Risk Factors to Consider

2021 ◽  
Author(s):  
Habib El-Khoury ◽  
Omran Saifi ◽  
Mohamad Chahrour ◽  
Salame Haddad ◽  
Khaled Ghanem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia ◽  
Cerebral Sinus Venous Thrombosis ◽  
Cerebral Sinus ◽  
Sinus Venous Thrombosis

Background: Cerebral Sinus Venous Thrombosis (CSVT) is one of many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, consensus management, no recommendations exist to target the population at risk. Methods: This is a retrospective chart review of 229 consecutive patients diagnosed with ALL and aged 1–21 years, treated at the Children’s Cancer Institute (CCI) between October 2007 and February 2017. Results: The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high risk disease, maximum Triglyceride (TG) level of > 615 mg/dL, presence of mediastinal mass, and larger body surface area. With multivariate analysis, the only statistically significant risk factors were maximum TG level, body surface area (BSA), presence of mediastinal mass, and risk stratification (intermediate/high risk). Conclusion: Our study was able to unveil TG level of > 615 mg/dL, mediastinal mass, and a larger body surface area as novel risk factors that have not been previously discussed in the literature.

scholarly journals Heterogeneity of presenting features and their relation to treatment outcome in 120 children with T-cell acute lymphoblastic leukemia

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 174-179 ◽  
Author(s):  
CH Pui ◽  
FG Behm ◽  
B Singh ◽  
MJ Schell ◽  
DL Williams ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia ◽  
Patients Âgés ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Leukocyte Counts ◽  
Risk Of Treatment

Abstract Presenting features of 120 consecutive children with T-cell acute lymphoblastic leukemia (ALL), representing 15% of all patients diagnosed as having ALL during the study period, were analyzed to determine relationships with treatment outcome. Patients' ages ranged from 1.7 to 18.8 years (median, 10.3 years) and their leukocyte counts from 1.7 to 1,070 x 10(9)/L (median, 100 x 10(9)/L). Central nervous system (CNS) leukemia was present in 12.5% of the cases, a mediastinal mass in 61%, and L2 lymphoblast morphology in 32%. A relatively high proportion of cases, 26%, had normal karyotypes at presentation. Of the cases tested, membrane CD1 expression was found in 38% of cases, CD3 in 33%, CD4 in 50%, CD5 in 94%, CD8 in 55%, and CD10 in 35%. Four presenting features were found to confer an increased risk of treatment failure: age greater than or equal to 15 years, L2 lymphoblast morphology, abnormal karyotype, and membrane CD3 expression. This study illustrates the heterogeneity of presentations of childhood T-cell ALL and suggests that the relative importance of risk factors in ALL differs according to immunophenotype and treatment strategy.

scholarly journals Homozygous Deletion of the p16/MTS1 Gene in Pediatric Acute Lymphoblastic Leukemia Is Associated With Unfavorable Clinical Outcome

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 4161-4166 ◽  
Author(s):  
Ursula R. Kees ◽  
Paul R. Burton ◽  
Changlong Lü ◽  
David L. Baker
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Clinical Outcome ◽  
Lymphoblastic Leukemia ◽  
Homozygous Deletion ◽  
Cell Phenotype ◽  
P16 Gene ◽  
Childhood All ◽  
Risk Of Death ◽  
Increased Risk

Abstract The p16 gene (MTS1, CDKN2, p16INK4A, CDKI) encoding an inhibitor of cyclin-dependent kinase 4 (cdk4) has been found to be deleted in various types of tumors, including leukemia, and is thought to code for a tumor suppressor gene. Our preliminary findings on eight pediatric patients with acute lymphoblastic leukemia (ALL) suggested that the survival of patients carrying a homozygous p16 gene deletion was significantly inferior to that of those without a deletion. The present study on 48 patients tested the hypothesis that the clinical outcome for pediatric ALL patients is correlated with the presence or absence of the p16 gene. Overall, nine of 48 children (18.3%) carried a homozygous p16 deletion. Such deletions were significantly more common (P = .003) among T-ALL patients (five of eight, 62.5%) than among precursor-B-ALL patients (four of 40, 10.0%). Of nine patients exhibiting p16 deletions, eight (88.9%) were classified as high-risk patients by the recognized prognostic factors of age, white blood cell count, and T-cell phenotype. The 4-year event-free survival in the study population as a whole was 72.7%. Without adjustment for other risk factors (univariate model), the presence of a homozygous p16 deletion was associated with a markedly increased probability of both relapse (P = .0003) and death (P = .002). These findings raise the question of whether the p16 deletion itself confers an increased risk of relapse after adjusting for the known risk factors. In this analysis, the estimated risk multiplier factor for relapse in patients carrying the p16 deletion was 14.0 (P = .0004) and for the risk of death 15.6 (P = .0008). We therefore conclude that the presence of a homozygous p16 deletion may well be an important risk factor for both relapse and death in childhood ALL, and that its prognostic effect is not a consequence of confounding by other factors already known to influence outcome in this disease.

scholarly journals Risk Factors for Induction Related Mortality in Adults Patients with Acute Lymphoblastic Leukemia: Report from a Hispanic Population

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5162-5162
Author(s):  
Sergio I Inclan-Alarcon ◽  
Christianne Bourlon ◽  
Oscar Manuel Fierro-Angulo ◽  
Jesus A Garcia-Ramos ◽  
Santiago Riviello-Goya ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Adult Patients ◽  
Hispanic Population ◽  
Increased Risk ◽  
The Impact ◽  
Hispanic Adult

Abstract Introduction Acute lymphoblastic leukemia (ALL) represents 20-30% of acute leukemia in adults. Higher incidence and inferior outcomes in Hispanic population have been described. In Latin Americans induction mortality (IM) is a major cause of death representing 20-50% vs.7-11% in developed countries. Our aim was to determine risk factors (RF) related to IM in ALL Hispanic adult patients. Methods We retrospectively analyzed clinical data of ≥18yo patients with ALL diagnosed and treated at our institution within 2009 and 2016. Results A total of 170 patients were included. Median age was 29 years (16-70), 64% were AYA, 96.8% had B-cell ALL, and 62.3% received Hyper-CVAD. IM rate was 13.4%. In 64.1% IM was related to an infectious cause. The most frequent infection was pneumonia (39.8%). Gram-negative etiology was more prevalent (35.5% vs. 10.2%), however, IM rate was higher in gram-positive infections (26.3% vs .13.6%; p=.028). RF related to IM in univariate analysis were: CNS involvement (OR4.6,95%IC2.8-9.5;p=<.001), tumor lysis syndrome (TLS) (OR 5.6, 95% CI 2.2-14.1; p=<.001), need for dialysis (OR 28.9, 95% CI 5.3-157.1; p=<.001), primary hypertension (OR 3.5, 95% CI 1.0-12.7; p=.052), shock status (OR 10.3, 95% CI 3.9-27.3; p=<.001), ECOG³2 (OR 1.9, 95% IC 1.1-3.4; p=.022), T-ALL (OR 2.2, 95% IC 1.1-4.3; p=.026), Hyper-CVAD (OR 1.9, 95% IC 1.1-3.8; p=0.51), ventilation assistance (OR 7.7, 95% IC 2.8-21; p=<.001), and vasopressor use (OR 7.6, 95% IC 2.8-20.6; p=<.001). In multivariate analysis TLS, need for dialysis and shock, kept statistical significance. Conclusions To our knowledge, this is the largest study that evaluates the impact over IM of biological, social, and economic factors in Hispanic adult patients with ALL. We identified factors not previously described such as hypertension and need for dialysis. Multicenter prospective studies most be urged to asses and validate these RF, and design a bedside prognostic score that can predict an increased risk of IM at ALL diagnosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Risk factors for surgical site infections in neurosurgery

2019 ◽  
Vol 101 (3) ◽  
pp. 220-225 ◽  
Author(s):  
S Patel ◽  
D Thompson ◽  
S Innocent ◽  
V Narbad ◽  
R Selway ◽  
...  
Keyword(s):  
Risk Factors ◽  
Significant Risk ◽  
Surgical Site Infections ◽  
Reoperation Rate ◽  
High Morbidity ◽  
Clinical Notes ◽  
Increased Risk ◽  
Public Data ◽  
Potential Risk Factors ◽  
Risk Patients

Introduction Surgical site infections (SSIs) are of profound significance in neurosurgical departments, resulting in high morbidity and mortality. There are limited public data regarding the incidence of SSIs in neurosurgery. The aim of this study was to determine the rate of SSIs (particularly those requiring reoperation) over a seven-year period and identify factors leading to an increased risk. Methods An age matched retrospective analysis was undertaken of a series of 16,513 patients at a single centre. All patients who required reoperation for suspected SSIs within a 7-year period were identified. Exclusion criteria comprised absence of infective material intraoperatively and patients presenting with primary infections. Clinical notes were reviewed to confirm presence or absence of suspected risk factors. Results Of the 16,513 patients in the study, 1.20% required at least one further operation to treat a SSI. Wound leak (odds ratio [OR]: 27.41), dexamethasone use (OR: 3.55), instrumentation (OR: 2.74) and operative duration >180 minutes (OR: 1.85) were statistically significant risk factors for reoperation. Conclusions This is the first UK study of such a duration that has documented a SSI reoperation rate in a cohort of this size. Various risk factors are associated with the development of SSIs, making it essential to have robust auditing and monitoring of high risk patients to ensure excellent standards of healthcare. Departmental and public registers to record all SSIs may be beneficial, particularly for those treated solely by general practitioners, allowing units to address potential risk factors prior to surgical intervention.

scholarly journals Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years

Blood ◽  
2018 ◽  
Vol 131 (22) ◽  
pp. 2475-2484 ◽  
Author(s):  
Cecilie Utke Rank ◽  
Nina Toft ◽  
Ruta Tuckuviene ◽  
Kathrine Grell ◽  
Ove Juul Nielsen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymph Nodes ◽  
Mediastinal Mass ◽  
Absolute Risk ◽  
Lymphoblastic Leukemia ◽  
Aged Patients ◽  
Pediatric Hematology ◽  
Hazard Ratios ◽  
Cerebral Sinus Venous Thrombosis ◽  
Age Range

Abstract Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N = 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P &lt; .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P &lt; .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P &lt; .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P = .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged lymph nodes, 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P &lt; .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P = .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P = .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P ≤ .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.

The Development Of Venous Thromboembolism May Increase The Risk Of Osteonecrosis In Children With Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3864-3864
Author(s):  
Badhiwala H. Jetan ◽  
Trishana Nayiager ◽  
Uma H. Athale
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Older Age ◽  
Regression Analyses ◽  
Female Ratio ◽  
Increased Risk ◽  
The Impact

Abstract Background Osteonecrosis (ON) is a severely disabling complication of anti-leukemic therapy, specifically long-term corticosteroid use. A hypercoagulable state is thought to underlie corticosteroid-related ON. Children with acute lymphoblastic leukemia (ALL) are also at increased risk of venous thromboembolism (VTE), indicating underlying hypercoagulability in this disease entity. Hence, we explored the relationship between ON and VTE, along with the association of ON with other variables, including age and asparaginase (ASP) therapy, in children with ALL. Methods Health records of children (< 18 yrs.) with de novo ALL treated at McMaster Children’s Hospital from 1992 to 2010 were reviewed. Patients were treated according to Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols. Data regarding demographics, leukemia diagnosis and therapy, development and characteristics of ON and VTE, and thrombophilia work-up, if any, were collected from computer records and chart review. Osteonecrosis was diagnosed by plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging, and/or technetium-99m (99mTc) bone scan. We included ON diagnosed during therapy and/or at any point during post-treatment follow-up. Standard radiological measures, including venous Doppler ultrasound and/or venography (conventional, CT, MR), confirmed VTE. We included only clinically significant thromboembolic events, defined as symptomatic VTE, or asymptomatic VTE requiring anticoagulation, developing during ALL therapy. Logistic regression analyses were performed to identify possible predictors of ON. Odds ratios (ORs) with 95% confidence intervals (CIs) and corresponding p-values were determined. Results Mean age of the study cohort (n = 208) was 5.4 years and male/female ratio 1.2:1. Seventy-eight (37.5%) patients had high-risk (HR) ALL and 127 (61.1%) received dexamethasone (DEX) as post-induction steroid. One hundred and sixty-two (77.9%) patients received E. coli ASP, 19 (9.1%) Erwinia ASP, and 27 (13.0%) PEG ASP. Twenty-one (10.1%) children developed ON. Joints affected by ON included the ankle in 11 subjects, knee in 10, hip in 8, and heel in one. Fourteen of the 21 patients (66.7%) had involvement of more than one joint. All patients were diagnosed with ON during ALL treatment, with the average being 69.2 weeks following ALL diagnosis. Forty-two (20.2%) subjects had a VTE while receiving therapy at an average of 29.4 weeks after ALL diagnosis. Nine patients had cerebral sinovenous thrombosis, 7 deep vein thrombosis (DVT), and one pulmonary embolism (PE). Twenty-six patients developed a central venous line (CVL)-related VTE. Results of univariate logistic regression analyses for osteonecrosis are presented in Table 1. VTE strongly predicted development of ON – OR 8.85 (95% CI 3.37–23.25, p< 0.001). Thirteen (31.0%) patients with VTE developed ON compared to 8 (4.8%) of 166 subjects without VTE. In 10 of 13 (76.9%) patients who developed both VTE and ON, the diagnosis of VTE preceded that of ON. Given that older age is a known risk factor for both VTE and ON, we conducted a multivariate analysis, which confirmed that age, ASP type, and VTE were independent, significant risk factors for ON (Table 2). Conclusion In addition to the known impact of older age, we identified VTE and type of ASP as independent risk factors for ON in children with ALL. These observations suggest overlap in the etiopathogenesis of ON and VTE. We recommend larger, prospective studies to confirm the association of VTE and PEG ASP with ON and to assess the impact of hypercoagulability on the development of ON. This in turn may help develop preventive strategies (e.g., thromboprophylaxis) for ALL-associated ON. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Asparaginase Discontinuation on Outcome in Childhood Acute Lymphoblastic Leukemia: A Report From the Children’s Oncology Group

2020 ◽  
Vol 38 (17) ◽  
pp. 1897-1905 ◽  
Author(s):  
Sumit Gupta ◽  
Cindy Wang ◽  
Elizabeth A. Raetz ◽  
Reuven Schore ◽  
Wanda L. Salzer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Early Response ◽  
Oncology Group ◽  
Increased Risk ◽  
Risk Patients ◽  
Landmark Analyses ◽  
The Impact

PURPOSE Asparaginase (ASNase) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued because of toxicity. Erwinia chrysanthemi ASNase ( Erwinia) substitution was approved in 2011 for allergic reactions. Erwinia has, however, been intermittently unavailable because of drug supply issues. The impact of Erwinia substitution or complete ASNase discontinuation is unknown. METHODS Patients aged 1-30.99 years in frontline Children’s Oncology Group trials for B-cell acute lymphoblastic leukemia between 2004 and 2011 (National Cancer Institute [NCI] standard risk [SR]: AALL0331; NCI high risk: AALL0232) were included. The number of prescribed pegaspargase (PEG-ASNase) doses varied by trial and strata. Maintenance therapy did not contain ASNase. Landmark analyses at maintenance compared disease-free survival (DFS) among those receiving all prescribed PEG-ASNase doses versus switching to Erwinia but receiving all doses versus not receiving all ASNase doses. RESULTS We included 5,195 AALL0331 and 3,001 AALL0232 patients. The cumulative incidence of PEG-ASNase discontinuation was 12.2% ± 4.6% in AALL0331 and 25.4% ± 0.8% in AALL0232. In multivariable analyses, NCI high-risk patients not receiving all prescribed ASNase doses had inferior DFS (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.9; P = .002) compared with those receiving all prescribed PEG-ASNase doses. Patients with Erwinia substitution who completed subsequent courses were not at increased risk (HR, 1.1; 95% CI, 0.7 to 1.6; P = .69). NCI SR patients who discontinued ASNase were not at elevated risk (HR, 1.2; 95% CI, 0.9 to 1.6; P = .23), except when restricted to those with slow early response, who were prescribed more ASNase because of therapy intensification (HR, 1.7; 95% CI, 1.1 to 2.7; P = .03). CONCLUSION Discontinuation of ASNase doses is associated with inferior DFS in higher-risk patients. Our results illustrate the severe consequences of Erwinia shortages.

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