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 < .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 < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .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 < .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.

scholarly journals Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age

2020 ◽  
Vol 38 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Cecilie U. Rank ◽  
Benjamin O. Wolthers ◽  
Kathrine Grell ◽  
Birgitte K. Albertsen ◽  
Thomas L. Frandsen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Older Children ◽  
Pediatric Hematology ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Leukemic Relapse ◽  
First Time ◽  
Risk Of Relapse

PURPOSE Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored. PATIENTS AND METHODS We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. RESULTS Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse. CONCLUSION Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.

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 SIGNIFICANCE OF MEDIASTINAL MASS (MM) IN ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

1974 ◽  
Vol 8 (4) ◽  
pp. 408-408
Author(s):  
Yaddanapudi Ravindranath ◽  
Joseph Kaplan ◽  
W W Zuelzer
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia

Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association.

1995 ◽  
Vol 13 (2) ◽  
pp. 352-358 ◽  
Author(s):  
C Uderzo ◽  
M G Valsecchi ◽  
A Bacigalupo ◽  
G Meloni ◽  
C Messina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Pediatric Hematology ◽  
First Relapse

PURPOSE To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized. PATIENTS AND METHODS All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors. RESULTS In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (> 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse). CONCLUSION Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.

Ovarian and multiple lymph nodes recurrence of acute lymphoblastic leukemia: a case report and review of literature

2008 ◽  
Vol 24 (11) ◽  
pp. 1269-1273 ◽  
Author(s):  
Jong Woon Kim ◽  
Moon Kyoung Cho ◽  
Cheol Hong Kim ◽  
Woo Dae Kang ◽  
Hoon Kook ◽  
...  
Keyword(s):  
Case Report ◽  
Acute Lymphoblastic Leukemia ◽  
Lymph Nodes ◽  
Lymphoblastic Leukemia ◽  
Review Of 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.

Obesity and Outcome in Pediatric Acute Lymphoblastic Leukemia

2007 ◽  
Vol 25 (15) ◽  
pp. 2063-2069 ◽  
Author(s):  
Anna M. Butturini ◽  
Frederick J. Dorey ◽  
Beverly J. Lange ◽  
David W. Henry ◽  
Paul S. Gaynon ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Prognostic Variables ◽  
Free Survival ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Cancer Group ◽  
Hazard Ratios ◽  
Nonobese Patients

PurposeTo evaluate the effect of obesity (defined as a body mass index > 95th percentile for age and sex at diagnosis) on outcome of pediatric acute lymphoblastic leukemia (ALL).Patients and MethodsWe retrospectively analyzed data from 4,260 patients with newly diagnosed ALL enrolled from 1988 to 1995 onto five concurrent Children's Cancer Group studies. Results were verified in a second cohort of 1,733 patients enrolled onto a sixth study from 1996 to 2002.ResultsThe 1988 to 1995 cohort included 343 obese and 3,971 nonobese patients. The 5-year event-free survival rate and risk of relapse in obese versus nonobese patients were 72% ± 2.4% v 77% ± 0.6% (P = .02) and 26 ± 2.4 v 20 ± 0.6 (P = .02), respectively. After adjusting for other prognostic variables, obesity's hazard ratios (HRs) of events and relapses were 1.36 (95% CI, 1.04 to 1.77; P = .021) and 1.29 (95% CI, 1.02 to 1.56; P = .04), respectively. The effect of obesity was prominent in the 1,003 patients ≥ 10 years old at diagnosis; in this subset, obesity's adjusted HRs of events and relapses were 1.5 (95% CI, 1.1 to 2.1; P = .009) and 1.5 (95% CI, 1.2 to 2.1; P = .013), respectively. In a second cohort of 1,160 patients ≥ 10 years old, obesity's adjusted HRs of events and relapses were 1.42 (95% CI, 1.03 to 1.96; P = .032) and 1.65 (95% CI, 1.13 to 2.41; P = .009), respectively. The effect of obesity on outcome was unrelated to changes in chemotherapy doses, length of intervals between chemotherapy cycles, or incidence and severity of therapy-related toxicity.ConclusionObesity at diagnosis independently predicts likelihood of relapse and cure in preteenagers and adolescents with ALL.

Investigation of Epidemiologic Factors in Children with Acute Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3948-3948
Author(s):  
Oznur Yilmaz ◽  
Cetin Timur ◽  
Asim Yoruk ◽  
Muferet Erguven ◽  
Elif Aktekin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Ventilatory Support ◽  
Control Group ◽  
Healthy Children ◽  
High Concentration ◽  
Pediatric Hematology ◽  
Epidemiologic Factors ◽  
Significant Difference ◽  
The Mean

Abstract In this study, we aimed to investigate epidemiologic factors in children with Acute Lymphoblastic leukemia (ALL). The parents of 105 children diagnosed and treated as ALL between the years 1997 –2007 in our Clinic of Pediatric Hematology-Oncology were questioned and results were compared with control group that consisted of 102 healthy children with similar age and gender. The mean age of the patients was 8.57 ± 3.95 years. The mean age at diagnosis was 5.87 ± 3.73 years. There was no significant difference between the groups in terms of type of delivery, birth weight, asphyxia at birth, resuscitation with high-concentration oxygen and ventilatory support (p&gt;0.05). There was also no significant difference between the groups in terms of duration of breast feeding. The rate of exposure to infections prior to diagnosis was higher in control group (p:0.003). Besides that, the rate of going to nursery was also significantly higher in control group (p:0.014). There was no difference between the groups in terms of X-ray exposure (p&gt;0.05). In conclusion over-protection from infectious agents in and delay in meeting with some specific agents seems to increase ALL risk. Infections in early infantile period can be protective against leukemia. There has to be more extended studies on this subject.

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