Biology of childhood acute lymphoblastic leukemia (ALL) in low/middle-income countries-A case for using age at diagnosis for defining low-risk ALL

2015 ◽  
Vol 62 (10) ◽  
pp. 1687-1688
Author(s):  
Yaddanapudi Ravindranath
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Low Risk ◽  
Age At Diagnosis ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Middle Income ◽  
Middle Income Countries ◽  
Low Middle Income Countries

Infectious complications in children with acute lymphoblastic leukemia treated in low-middle-income countries

2015 ◽  
Vol 8 (5) ◽  
pp. 627-645 ◽  
Author(s):  
Miguela A Caniza ◽  
Carla Odio ◽  
Sheena Mukkada ◽  
Miriam Gonzalez ◽  
Francesco Ceppi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Infectious Complications ◽  
Middle Income ◽  
Middle Income Countries ◽  
Low Middle Income Countries

scholarly journals Randomized, Parallel Group, Open-Label Bioequivalence Trial of Intramuscular Pegaspargase in Patients With Relapsed Acute Lymphoblastic Leukemia

2020 ◽  
pp. 1009-1016
Author(s):  
Manjunath Nookala Krishnamurthy ◽  
Gaurav Narula ◽  
Khushboo Gandhi ◽  
Ankita Awase ◽  
Ruta Pandit ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Reference Product ◽  
Lymphoblastic Leukemia ◽  
High Price ◽  
Maximum Plasma ◽  
Open Label ◽  
Middle Income ◽  
Middle Income Countries ◽  
Parallel Group ◽  
Low And Middle Income

PURPOSE Pegylated asparaginase is comparatively safer than native asparaginase in the management of acute lymphoblastic leukemia (ALL). However, the high price and nonavailability in low- and middle-income countries limits its use. In 2014, the first generic of pegaspargase (Hamsyl) was approved in India for use as a second-line treatment option for ALL. The aim of this study was to assess whether the generic pegaspargase (the test product) was bioequivalent with the reference product (Oncaspar). PATIENTS AND METHODS This study was an open-label, parallel-group, comparative pharmacokinetic study in pediatric patients with relapsed ALL receiving their first dose (1,000 IU/m2) of pegaspargase administered intramuscularly. Patients were randomly assigned 1-to-1 to either the test or the reference product. The 2 formulations were considered equivalent if the 90% CIs for area under the plasma asparaginase activity–time curve (AUC0-t) geometric mean test-to-reference ratio was within 75% to 133%. RESULTS Twenty-nine patients (6-18 years of age) were enrolled in this study, of whom 24 completed the study criteria and were considered for safety analysis (5 patients were ineligible for the assessment). Three patients were excluded from analysis, because of presence of anti-asparaginase antibodies, leaving 21 patients who were considered for bioequivalence pharmacokinetics data. The point estimate of AUC0-t for the test-to-reference ratio was 95.05 (90% CI, 75.07% to 120.33%). Maximum plasma concentration, trough concentrations (day 14), half-life, volume of distribution, drug clearance, and changes in the asparagine and glutamine levels were not significantly different between products. Adverse events were comparable in both groups. CONCLUSION Generic and reference pegaspargase had equivalent pharmacokinetics with comparable safety. This could be a safe and cost-effective alternative for patients with ALL, especially in low- and middle-income countries.

scholarly journals Omics techniques and biobanks to find new biomarkers for the early detection of acute lymphoblastic leukemia in middle-income countries: a perspective from Mexico

2017 ◽  
Vol 74 (3) ◽  
pp. 227-232
Author(s):  
William Alejandro Aguirre-Guillén ◽  
Tania Angeles-Floriano ◽  
Briceida López-Martínez ◽  
Hortensia Reyes-Morales ◽  
Albert Zlotnik ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Early Detection ◽  
Lymphoblastic Leukemia ◽  
Middle Income ◽  
Middle Income Countries ◽  
New Biomarkers

scholarly journals Response Adapted Therapy in ETV6/RUNX1-Positive Childhood Acute Lymphoblastic Leukemia Treated per Modified St Jude Total XV Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Mayada Abu Shanap ◽  
Iyad Sultan ◽  
Amal Abu-Ghosh ◽  
Hasan Hashem ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Low Risk ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Standard Risk

Introduction: ETV6-RUNX1 is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a precursor-B phenotype. The presence of ETV6-RUNX1 has been associated with a relatively low rate of relapse in multiple studies. Relapses tend to occur late and have a better salvage rate than other ALL subtypes. Moreover, conflicting data in literature regarding the prognostic significance of ETV6-RUNX1 after accounting for age, initial count and treatment intensity. We sought to study the clinical features, therapy response in newly diagnosed ETV6-RUNX1-positive treated at King Hussein Cancer Center. Methods: Patients were treated per modified St Jude Total (XV) study, risk stratification was further refined by including minimal residual disease (MRD)measurements on day 15 and day 46 of remission induction therapy. Patients with the ETV6- RUNX1 fusion or hyperdiploidy without CNS or testicular disease and a satisfactory early MRD decline (<1% on day 15 and <0.01% on day 46) were classified as being low-risk for relapse and were treated on lower -risk arm regardless of age and leukocyte count. Results: Seventy patients (n=70) with ETV6-RUNX1-positive treated at our institution between May 2006 to October 2017. The median age at diagnosis, 5.8 years (range, 1.5-10.8). ETV6-RUNX1 was associated with favorable age between 1- and 6-years in 55 patients (79%), male gender in 41 patients (59%), initial leukocyte count <10 in 39 patients (56%), CNS status 1 in 100% of patients. The majority, n= 58 (83%) of patients had NCI standard risk (SR) and n=12 (17%) had NCI high risk (HR). Sixty-six patients (94%) had MRD <1% at day 15 and all patients achieved remission with MRD<0.01% at day 46 of remission induction. All patients were treated as LR ALL per modified St Jude total XV protocol. At median follow up of (36 months; range, 26 to 154), in the subgroups of ETV6-RUNX1-positive patients classified as NCI standard risk (SR)and NCI high risk (HR) the 5-year EFS estimates were 94.1% ± 3.2 and 82%±1(P=.13), 5-year OS estimates were 100% and 92% ± 8 (p=0.31) respectively. Conclusion: MRD treatment schema in ETV6/RUNX1 -positive patients have excellent outcomes if they achieved favorable response at day 15 and end of remission induction regardless of the age and Initial leukocyte count. Treatment reduction is feasible and declared safe for children with NCI-HR who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD post remission induction therapy. Disclosures No relevant conflicts of interest to declare.

Treatment-related mortality in children with acute lymphoblastic leukemia in a low-middle income country

2021 ◽  
Author(s):  
Rahat-Ul-Ain ◽  
Mahwish Faizan ◽  
Wasila Shamim
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Tumor Lysis Syndrome ◽  
Infection Prevention And Control ◽  
Middle Income ◽  
Female Ratio ◽  
Low Middle Income Countries ◽  
Treatment Related Mortality ◽  
Related Mortality

Objective: To determine the proportion of treatment-related mortality (TRM) among mortalities of Pediatric Acute Lymphoblastic Leukemia (ALL), to identify probable causes and risk factors. Methods: An observational; retrospective, cohort study. Pediatric patients of ALL who expired during treatment were enrolled. Death due to relapse and deaths before treatment were excluded. Retrospective data was collected from ward record and analyzed in SPSS 16. Results: Total 247 patients of ALL expired while 144 patients were enrolled as per inclusion criteria. The proportion of TRM was 58.3%. Median age was 5 years. Male-to-female ratio was 1.3:1. Commonest cause of TRM was sepsis (n=126, 87.5%), followed by hemorrhagic complications (n=11, 7.6%), drug toxicity (n=4, 2.8%), tumor lysis syndrome (n=2, 1.4%) and thromboembolism (n=1, 0.7%). Significant factors associated with TRM were weight-for-age, immunophenotype, reason for admission and absolute neutrophil count. Conclusion: Treatment-related mortality though potentially avoidable is still a major cause of death among pediatric patients of ALL in low-middle income countries. Sepsis is the most common cause and infection prevention and control is vital in improving survival. Best supportive care must be made available for the patients on induction chemotherapy, with concomitant malnutrition, high-risk immunophenotype and profound neutropenia. Continuous...

scholarly journals Longitudinal Assessment of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated on a Contemporary Chemotherapy Protocol

2016 ◽  
Vol 34 (11) ◽  
pp. 1239-1247 ◽  
Author(s):  
Lisa M. Jacola ◽  
Kevin R. Krull ◽  
Ching-Hon Pui ◽  
Deqing Pei ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Neurocognitive Function ◽  
Attention Problems ◽  
Elevated Risk ◽  
Age At Diagnosis ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Neurocognitive Outcomes ◽  
Age Appropriate ◽  
Prospective Longitudinal

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) treated with CNS-directed chemotherapy are at risk for neurocognitive deficits. Prospective longitudinal studies are needed to clarify the neurodevelopmental trajectory in this vulnerable population. Methods Patients enrolled in the St. Jude Total Therapy Study XV, which omitted prophylactic cranial radiation therapy in all patients, completed comprehensive neuropsychological assessments at induction (n = 142), end of maintenance (n = 243), and 2 years after completion of therapy (n = 211). We report on longitudinal change in neurocognitive function and predictors of neurocognitive outcomes 2 years after completing therapy. Results Neurocognitive function was largely age appropriate 2 years after completing therapy; however, the overall group demonstrated significant attention deficits and a significantly greater frequency of learning problems as compared with national normative data (all P ≤ .005). Higher-intensity CNS-directed chemotherapy conferred elevated risk for difficulties in attention, processing speed, and academics (all P ≤ .01). The rate and direction of change in performance and caregiver-reported attention difficulties differed significantly by age at diagnosis and sex. End-of-therapy attention problems predicted lower academic scores 2 years later, with small to moderate effect sizes (│r│= 0.17 to 0.25, all P ≤ .05). Conclusion Two years after chemotherapy-only treatment, neurocognitive function is largely age appropriate. Nonetheless, survivors remain at elevated risk for attention problems that impact real-world functioning. Attention problems at the end of therapy predicted decreased academics 2 years later, suggesting an amplified functional impact of discrete neurocognitive difficulties. Age at diagnosis and patient sex may alter neurocognitive development in survivors of childhood ALL treated with chemotherapy-only protocols.

Sign in / Sign up

Export Citation Format

Share Document