scholarly journals Clinical Characteristics and Outcome After Induction of Chemotherapy in Pediatric Acute Lymphoblastic Leukemia: A Descriptive and Correlational Study From the West Bank of Palestine

2020 ◽  
Author(s):  
Ramzi Shawahna
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Clinical Characteristics ◽  
Lymphoblastic Leukemia ◽  
White Blood Cells ◽  
P Value ◽  
Published Data ◽  
Bone Marrow Biopsies ◽  
Progress Notes ◽  
Pediatric All

Abstract BackgroundPediatric acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer among children. This study was conducted to describe and correlate the clinical characteristics and outcomes of treatment of patients with pediatric ALL in the main referral hospital in Palestine. MethodsIn this single-center, retrospective, observational study, paper-based and electronic medical records of patients with pediatric ALL who received induction chemotherapy were reviewed. The sociodemographic variables, details of patient history, findings of physical examinations, daily progress notes, bone marrow biopsies, flow cytometry, and cytogenetics of patients were collected. ResultsComplete data of 69 patients were included in this analysis. The majority (79.7%) of the patients had B-ALL phenotype, 22 (31.9%) had abdominal pain, 37 (53.6%) had fever, 30 (43.5%) complained of bone pain, 50 (72.5%) had pallor, 9 (13.0%) had anorexia, 34 (49.3%) had hepatomegaly, 34 (49.3%) had splenomegaly, and 15 (21.7%) complained of bleeding symptoms. After induction chemotherapy, remission was experienced by the vast majority of the patients and 5 (7.2%) experienced relapse after receiving chemotherapy. The vast majority of the patients (96%) had CNS status 1, 1.4% had CNS status 2, and 2.9% had CNS status 3. Cytogenetics for patients with B-ALL phenotype indicated that 10 (18.2%) patients had t(12,21) translocation, 5 (9.1%) had hyperdiploidy, 4 (7.3%) had t(1,19) translocation, and 2 (3.6%) had t(9,22) translocation. The initial white blood cells (p value < 0.001), absolute neutrophils (p value = 0.011), and hemoglobin (p value < 0.001) were significantly lower for patients with B-cell ALL. Platelet counts were significantly lower (p value = 0.012) in patients with splenomegaly and those with bleeding symptoms (p value = 0.008). Presence of pollar was positively associated (p value = 0.035) with T-cell ALL. Presence of hepatomegaly was positively associated (p value < 0.001) with splenomegaly.ConclusionOverall, this study provides insights into the clinical characteristics and outcomes of induction chemotherapy in Palestinian patients with pediatric ALL. The characteristics of ALL among Palestinians were comparable to their peers in the region. The outcomes of induction chemotherapy were also comparable to other published data for ALL patients.

scholarly journals Clinical characteristics and outcomes of patients with pediatric acute lymphoblastic leukemia after induction of chemotherapy: a pilot descriptive correlational study from Palestine

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ramzi Shawahna ◽  
Sultan Mosleh ◽  
Yahya Odeh ◽  
Rami Halawa ◽  
Majd Al-Ghoul
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Blood Cells ◽  
Clinical Characteristics ◽  
Lymphoblastic Leukemia ◽  
White Blood Cells ◽  
P Value ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

Abstract Objective Pediatric acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer among children. This study was conducted to describe and correlate the clinical characteristics and outcomes of treatment of patients with pediatric ALL in the main referral hospital in Palestine. Results Complete data of 69 patients were included in this analysis. The majority (79.7%) of the patients had B-ALL phenotype. After induction chemotherapy, remission was experienced by the vast majority of the patients and 5 (7.2%) experienced relapses. Cytogenetics for patients with B-ALL phenotype indicated that 10 (18.2%) patients had t(12, 21) translocation, 5 (9.1%) had hyperdiploidy, 4 (7.3%) had t(1, 19) translocation, and 2 (3.6%) had t(9, 22) translocation. The initial white blood cells (p value < 0.001), absolute neutrophils (p value = 0.011), and hemoglobin (p value < 0.001) were significantly lower in patients with B-cell ALL. Platelet counts were significantly lower (p value = 0.012) in patients with splenomegaly and those with bleeding symptoms (p value = 0.008). Presence of palmar pollar was positively associated (p value = 0.035) with T-cell ALL. Presence of hepatomegaly was positively associated (p value < 0.001) with splenomegaly.

scholarly journals Assessment of obesity and hepatic late adverse effects in the Egyptian survivors of pediatric acute lymphoblastic leukemia: single center study

2017 ◽  
Vol 9 (1) ◽  
pp. e2017026 ◽  
Author(s):  
Farida El-Rashedy ◽  
Mahmoud Ahmed El-Hawy ◽  
Sally El Hefnawy ◽  
Mona Mohammed
Keyword(s):  
Hepatitis C ◽  
Acute Lymphoblastic Leukemia ◽  
Adverse Effects ◽  
Liver Enzymes ◽  
Lymphoblastic Leukemia ◽  
Overweight And Obesity ◽  
Direct Bilirubin ◽  
P Value ◽  
Late Adverse Effects ◽  
Pediatric All

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates reaching 80% emphasizes the necessity to determine treatment related long-term effects. The aim of this study is to estimate the prevalence of overweight, obesity and hepatic late adverse effects in a cohort of ALL survivors treated at the Hematology and Oncology Unit, Pediatrics Department, Menoufia University, Egypt.METHODS: In this case control study, height, weight and body mass index (BMI) were assessed for 35 pediatric ALL survivors and 15 healthy children. These parameters were plotted on the growth and WHO standard deviation charts for both males and females. Overweight and obesity were defined by BMI > 85th and 95th percentile respectively. Laboratory investigations were done in the form of iron profile, liver enzymes, total and direct bilirubin levels, serum urea &creatinine and detection of hepatitis C virus antibodies by ELISA.RESULTS: The weight and BMI were significantly higher in the survivors than controls (P value =0.002 and 0.039 respectively). ALT, total & direct bilirubin, serum ferritin and transferrin saturation were significantly higher in the survivors than the controls (P value = 0.03, 0.036, 0.044, 0.006 and 0.03 respectively). Ten (28.6%) of survivors had hepatitis C antibodies with none (0%) of controls (P value =0.02)CONCLUSIONS: Pediatric ALL survivors are at increased risk of overweight/obesity, hepatic dysfunction in the form of elevated liver enzymes, bilirubin levels and C viral hepatitis. Screening of those survivors for such complications should be considered.Key words: ALL- Survivors – Obesity- Liver.

Participation in a Clinical Trial Does Not Impact Outcome in Pediatric Acute Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1318-1318
Author(s):  
Carl Koschmann ◽  
Doug S Hawkins ◽  
Blythe Thomson
Keyword(s):  
Clinical Trial ◽  
Acute Lymphoblastic Leukemia ◽  
Research Study ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Study Participation ◽  
Single Institution ◽  
Home State ◽  
Pediatric All

Abstract Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Over the past four decades, the outcome for pediatric ALL has rapidly improved secondary to the participation of children on clinical trials, resulting in standardization of the treatment. Some have argued that the best outcome results from participation in a pediatric clinical trial. To address the potential benefits and barriers to participation in a clinical trial, we analyzed clinical trial participation in pediatric ALL at a large single institution. Methods: We evaluated 322 ALL patients &lt; 22 years old at diagnosis who receive their initial therapy at Seattle Children’s Hospital Regional Medical Center (S-CHRMC) between January 1997 and December 2005. Using a retrospective chart review, we analyzed the following variables: study participation (SP) or non-participation (NP) in an ALL therapeutic study, gender, race, patient immunophenotype, risk group (standard risk (SR), high risk (HR) or infant), home state, and distance of primary residence from S-CHRMC. S-CHRMC is the largest pediatric cancer center in the Pacific Northwest, with referrals from Washington, Alaska, Montana, Idaho and Wyoming. Events were defined as relapse or death from any cause. Results: The overall 5 year event free survival (EFS) was 78% (+/− 2.5%). 157 patients participated in a treatment research study (49%). Only risk group was associated with EFS. SP and NP had similar EFS. Gender, race, immunophenotype, home state, or distance from primary residence were not associated with outcome. There was no difference in study participation by gender, race, home state, or distance of primary residence. There were trends to increased participation in SR vs HR (54% vs 35%, p value 0.15) and B lineage vs T lineage (50% vs 35%, p value 0.11). Variable n 5 year EFS p value Study participation No 165 76 (+/− 3.9) 0.47 Yes 157 81 (+/− 3.3) Risk group SR 175 85 (+/− 3.0) HR 132 73 (+/− 4.2) (0.038 to SR) Infant 15 59 (+/−12.9) (0.011 to SR) Discussion: Participation in a research study for treatment of pediatric ALL was not associated with improved outcome in our large single institution series. Study participation was not different by clinical features, including distance to the primary residence. Strict standardization of treatment for all patients may contribute to the similar outcome for SP and NP.

Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients

Blood ◽  
2006 ◽  
Vol 108 (7) ◽  
pp. 2216-2222 ◽  
Author(s):  
Vanesa Caruso ◽  
Licia Iacoviello ◽  
Augusto Di Castelnuovo ◽  
Sergio Storti ◽  
Guglielmo Mariani ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Prospective Studies ◽  
Lymphoblastic Leukemia ◽  
Meta Analysis ◽  
Epidemiologic Studies ◽  
Published Data ◽  
Induction Phase ◽  
Thrombotic Risk ◽  
Central Lines ◽  
Pediatric All

AbstractThe risk of thrombosis in children with acute lymphoblastic leukemia (ALL) reportedly ranges between 1% and 37%. Epidemiologic studies have usually been hampered by small numbers, making accurate estimates of thrombosis risk in ALL patients very difficult. The aim of this study was to better estimate the frequency of this complication and to define how the disease, its treatment, and the host contribute to its occurrence. We made an attempt to combine and analyze all published data on the association between pediatric ALL and thrombosis, by using a meta-analytic method. The rate of thrombosis in 1752 children from 17 prospective studies was 5.2% (95% CI: 4.2-6.4). The risk varies depending on several factors. Most of the events occurred during the induction phase of therapy. Lower doses of asparaginase (ASP) for long periods were associated with the highest incidence of thrombosis, as were anthracyclines and prednisone (instead of dexamethasone). The presence of central lines and of thrombophilic genetic abnormalities also appeared to be frequently associated with thrombosis. In conclusion, the overall thrombotic risk in ALL children was significant, and the subgroup analysis was able to identify high-risk individuals, a finding that will hopefully guide future prospective studies aimed at decreasing this risk.

scholarly journals Risk Factors of Acute Pancreatitis in Pediatric Acute Lymphoblastic Leukemia Patients: A Single-Center Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5077-5077 ◽  
Author(s):  
Soyoon MIN ◽  
Hyery Kim ◽  
Juhee Shin ◽  
Jin Kyung Suh ◽  
Sung Han Kang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Pancreatitis ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Induction Chemotherapy ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Pediatric All

Background: Acute pancreatitis during chemotherapy of acute lymphoblastic leukemia (ALL) is an often fatal complication which is mainly associated with asparaginase. Despite of the improvement of supportive care during treatment of ALL, the prediction of acute pancreatitis has not been feasible. The aim of this study was to identify the risk factors of acute pancreatitis in pediatric ALL patients. Patients and methods: This study included total 421 patients under 18 years old of age who were newly diagnosed with ALL and treated at Asan Medical Center Children's Hospital between January 2000 and December 2018. Patients in standard-risk group received a modified COG AALL0331 based treatment, and those in high-risk group received Korean multicenter high-risk ALL treatment. For national insurance coverage, native L-asparaginase was used as a first choice in all patients except patients who accepted the expanses of Pegylated-asparaginase (PEG). Patients who developed hypersensitivities to native asparaginase or PEGs, Erwinia-asparaginase was administered. Fibrinogen, triglyceride, amylase, lipase, and coagulation battery were checked before every asparaginases in all patients. The diagnosis and grading of acute pancreatitis were based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The cases of acute pancreatitis after relapse or allogenic hematopoietic stem cell transplantation were excluded. All the laboratory data were collected and analyzed retrospectively. Results: The incidence of acute pancreatitis in pediatric ALL was 3.3% (14 patients) and asparaginase associated acute pancreatitis was 2.8% (12 patients). Acute pancreatitis occurred in mainly in induction chemotherapy (n=8, 67%). Two patients were developed acute pancreatitis in consolidation chemotherapy, 1 in interim maintenance chemotherapy. Among 8 patients who developed acute pancreatitis in their induction chemotherapy, 1 patient was not associated with asparaginase. Among 14 patients, 2 patients were expired of disease progression and none of patient died of acute pancreatitis. Grade 2, 3 of acute pancreatitis patients were 6 and 8 respectively. There was no grade 5 acute pancreatitis. Eleven out of twelve patients who developed acute pancreatitis associated with asparaginase medication re-challenged asparaginase medication after experiencing acute pancreatitis. Among re-challenged patients, only 1 had second acute pancreatitis and discontinued asparaginase medication. There was no significant difference in incidence of acute pancreatitis with initial BSA, protein C, protein S, and age at diagnosis. Multivariate analysis identified prolonged activated partial thromboplastin time (aPTT) before acute pancreatitis in 1 week was significantly involved with risk factor of acute pancreatitis (p=0.013) Eight patients (67%) received a fresh frozen blood transfusion(FFP) before acute pancreatitis in a week. Conclusions: Prolonged aPTT and FFP transfusion are particularly at risk for acute pancreatitis in pediatric ALL patients. Cautious re-challenging asparaginase medication after experiencing grade 2 and grade 3 acute pancreatitis is needed. Early diagnosis and manage asparaginase-associated acute pancreatitis will contribute patients with sufficient effect of asparaginase medication. Disclosures No relevant conflicts of interest to declare.

scholarly journals Early Lifestyle Intervention for Obesity Prevention in Pediatric Survivors of Acute Lymphoblastic Leukemia

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2631 ◽  
Author(s):  
Zhang ◽  
Kelly ◽  
Du ◽  
Welch ◽  
Santacruz ◽  
...  
Keyword(s):  
Physical Activity ◽  
Acute Lymphoblastic Leukemia ◽  
Lifestyle Intervention ◽  
Lymphoblastic Leukemia ◽  
Practice Change ◽  
P Value ◽  
Feeding Practice ◽  
Phone Calls ◽  
Pediatric All ◽  
Change In Mean

Patients with pediatric acute lymphoblastic leukemia (ALL) experience rapid weight gain during treatment and increases in weight are maintained throughout treatment and beyond. Without prompt interventions, altered dietary and physical activity behaviors may become difficult to reverse, contributing to obesity risk long-term. Fifteen children, aged 3–9 years, diagnosed with pediatric ALL who were on maintenance therapy or within two years of treatment completion (mean BMI percentile: 70.4th) and one parent from each family, were enrolled into a 12-week lifestyle intervention delivered remotely through web-based sessions and phone calls with a lifestyle coach. Outcomes were assessed at baseline and end of the intervention. Thirteen of the 15 enrolled families (86.7%) completed the intervention. Parents reduced the “pressure to eat” feeding practice (change in mean score: −0.60, 95% CI: −1.12 to −0.07; p-value = 0.03) post intervention. Children increased the consumption of milk (0.54 serving/d, 0.02 to 1.07; p-value = 0.04) and percent of calories from protein (2.54%, 0.22 to 4.87%; p-value = 0.04) and reduced the consumption of potatoes (−0.16 serving/d, -0.30 to −0.03; p-value = 0.02). No significant changes were observed for children’s levels of physical activity, BMI, or waist circumference. Results from this pilot support the feasibility and preliminary efficacy of early lifestyle intervention among pediatric ALL survivors.

Steroid-Induced Hypertension during Induction Chemotherapy for Acute Lymphoblastic Leukemia in US Children's Hospitals

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3651-3651 ◽  
Author(s):  
Ian Bakk ◽  
Sarah O'Brien ◽  
Suzanne Reed ◽  
Terah Koch
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Sensitivity And Specificity ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Age Group ◽  
Pediatric Hospitals ◽  
Induced Hypertension ◽  
Pediatric All ◽  
Data Source

Abstract Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The induction phase of chemotherapy, including high-dose corticosteroids, is critical and effective as 98% of patients achieve remission after induction. It is generally understood that most non-life threatening side effects of chemotherapy during induction should be tolerated and treated with additional medication (if necessary) rather than reducing or discontinuing chemotherapeutic medication. Although hypertension (HTN) is a known possible complication of high-dose corticosteroids, the actual incidence and risk factors for this adverse event are poorly understood. Our objective was to utilize a national administrative data source to begin to answer these uncertainties. Methods: The Pediatric Health Information System (PHIS) database consists of inpatient information from 43 US free-standing pediatric hospitals representing 25% of US pediatric centers and the majority of tertiary care pediatric hospitals. The PHIS database includes de-identified demographic data, discharge diagnoses, and medications prescribed among other data. Our study examined all new cases of ALL from age 0 to 28 years from Jan 1, 2009 to Dec 31, 2013. We defined our population of ALL patients receiving induction chemotherapy as those who: 1) had a non-relapse ALL ICD-9 code (204.0, 204.00, 204.01) and 2) received induction chemotherapy medications within the first 14 days of admission. Patients receiving antihypertensive medication before or on the date of chemotherapy initiation were excluded from our population. Due to the unknown sensitivity and specificity of ICD-9 codes for hypertension in this patient population, we elected to define hypertension based on recorded use of anti-hypertensive medications rather than diagnostic codes. Results: We identified 4,917 unique patients who received induction chemotherapy for ALL. Of these patients, 13.0% received anti-hypertensive drugs during their admission. Adjusted logistic regression demonstrated increased odds of developing steroid-induced hypertension in obese patients [2.3; 95% CI: (1.42-3.71)] and those receiving anthracycline drugs [1.3; 95% CI: (1.004-1.67)]. Decreased odds of developing steroid-induced hypertension were independently associated with the 5 to 9 year age group [0.61; 95% CI: (0.49-0.76)] as compared to the 0 to 4 year age group. To assess the reliability of using ICD-9 codes to identify patients with hypertension, sensitivity and specificity were calculated. Using receipt of anti-hypertensive drugs as the gold standard, the sensitivity of ICD-9 codes to detect hypertension was 0.60 [95% CI: (0.56-0.64)] and specificity was 0.96 [95% CI: (0.96-0.97)]. Conclusion: To our knowledge, this was the first study of steroid-induced HTN in pediatric ALL patients using a national data source. We found that HTN is a common complication of induction ALL therapy. Increased risk for HTN was independently associated with obesity and anthracycline use. Although ICD-9 codes are very useful in ruling out hypertension, they are significantly less accurate in detecting those patients with hypertension. The lack of sensitivity of the HTN ICD-9 codes was notable and suggests underreporting of HTN by physicians. This study is limited as patient information is from a single inpatient admission. As cure rates of pediatric ALL approach 85%, the long-term effects of steroid-induced HTN deserves further study. Disclosures No relevant conflicts of interest to declare.

Higher Incidence of Treatment-Related Toxicities in Non-Hispanic Patients Undergoing Therapy for Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia on Dana-Farber Cancer Institute ALL Consortium Protocol 05-001

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 248-248 ◽  
Author(s):  
Justine Kahn ◽  
Sergio Barrera ◽  
Randy Davila ◽  
Emily Roberts ◽  
ZheZhen Jin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Newly Diagnosed ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Dana Farber Cancer Institute ◽  
Significant Difference ◽  
Hispanic Patients ◽  
Pediatric All

Abstract Background: Risk-adapted treatment strategies have contributed to excellent outcomes in pediatric acute lymphoblastic leukemia (ALL); however, treatment-associated acute and long-term toxicities persist. Therapy-associated toxicities of note in pediatric ALL are related to a treatment backbone that relies heavily on corticosteroids (prednisone and dexamethasone) and asparaginase (ASP). The most frequently observed toxicities include, but are not limited to, serious infection, pancreatitis, thrombosis and bony morbidities including osteonecrosis (ON) and fracture. Previous studies suggest that children of racial and ethnic minorities are at higher risk for treatment-associated toxicities. We assessed the incidence of treatment-related toxicities in Hispanic and non-Hispanic patients undergoing treatment for pediatric ALL. Patients and Methods: Retrospective cohort study investigating the incidence of treatment-related toxicities including infection, allergy to ASP, pancreatitis, thrombosis and bony morbidities in Hispanic and non-Hispanic children and adolescents with newly diagnosed ALL undergoing therapy on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 05-001. The ethnicity of each patient was designated at the time of study enrollment by research coordinators. Descriptive statistics were calculated, mean +/- SD for continuous variables and frequency and percentages for categorical variables. Toxicity rates were based on number of patients. Comparison between groups was done by Chi-square test or FisherÕs exact test and p -value < 0.05 was considered significant. Results: Between 2005 and 2011, 794 children and adolescents (ages 1 - 18 years) were enrolled on Protocol 05-001, 730 of whom were evaluable for this investigation: 150 Hispanic (18%), 580 non-Hispanic (73%). Sixty-four patients did not have ethnicity documented. There was no significant difference in disease-risk group, age or gender between the two groups. Weight was significantly higher in Hispanic patients (31.9 ± 24.4 kg in Hispanic and 26.9 ± 18.7 kg in non-Hispanic, p = 0.021). There was no significant difference in the incidence of ASP-related toxicities (allergy, pancreatitis, thrombosis) between Hispanic and non-Hispanic patients. There was no significant difference in the overall incidence of infection between the two groups (42% in Hispanic and 50% in non-Hispanic, p = 0.081). Non-Hispanic patients had significantly higher rates of opportunistic infection (Pneumocystis pneumonia) than Hispanic patients (0.7% in Hispanic and 4% in non-Hispanic, p = 0.041). A similar difference in the incidence of bacteremia between the two groups approached, but did not reach statistical significance (p = 0.052). The overall incidence of fracture in all patients was 14.5% and was significantly higher in non-Hispanic patients (6% in Hispanic and 16.7% in non-Hispanic, p < 0.001). The overall incidence of ON was 8.9% and was significantly higher in non-Hispanic patients (3.3% in Hispanic and 10.3% in non-Hispanic, p = 0.007). (Table 1) Conclusion: The incidence of opportunistic infections and bony morbidities was significantly higher in non-Hispanic patients undergoing treatment for pediatric ALL on the DFCI ALL Consortium Protocol 05-001. The risk for, and impact of therapy-related toxicities varies by a patientÕs treatment tolerance, perhaps as a function of age and gender or as a result of disease biology or genetic polymorphisms affecting drug metabolism. Additionally, non-biologic factors such as medication adherence and nutritional status may also contribute to toxicity incidence in patients undergoing treatment for pediatric ALL. Prospective studies to further investigate our findings are warranted. Table. All Patients, (N = 730) Non-Hispanic, (N = 580) Hispanic, (N = 150) p -value Overall Infection 353/730 (48.4%) 290/580 (50%) 63/150 (42%) 0.081 Bacteremia 289/730 (39.6%) 240/580 (41.4%) 49/150 (9.3%) 0.052 Opportunistic Infection 24/730 (3.3%) 23/580 (4%) 1/150 (0.7%) 0.041 Fracture 106/730 (14.5%) 97/580 (16.7%) 9/150 (6%) <0.001 Osteonecrosis 65/730 (8.9%) 60/580 (10.3%) 5/150 (3.3%) 0.007 Thrombosis* 36/730 (4.9%) 26/580 (4.5%) 10/150 (6.7%) 0.271 Pancreatitis* 78/730 (10.7%) 60/580 (10.3%) 18/150 (12%) 0.559 ASP Allergy* 76/730 (10.4%) 57/580 (9.8%) 19/150 (12.7%) 0.310 *ASP-related toxicity Disclosures No relevant conflicts of interest to declare.

Targeting Kinase-activating Genetic Lesions to Improve Therapy of Pediatric Acute Lymphoblastic Leukemia

2018 ◽  
Vol 25 (24) ◽  
pp. 2811-2825 ◽  
Author(s):  
Raffaella Franca ◽  
Natasa K. Kuzelicki ◽  
Claudio Sorio ◽  
Eleonora Toffoletti ◽  
Oksana Montecchini ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Hematologic Malignancy ◽  
Lymphoblastic Leukemia ◽  
Point Of View ◽  
Lymphoid Cells ◽  
Gene Encoding ◽  
Pediatric All ◽  
Blast Cells ◽  
Tk Inhibitors

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients’ lymphoblasts may harbor in fact several chromosomal alterations, some of which have prognostic and therapeutic value. Of particular importance is the translocation t(9;22)(q34;q11.2) that leads to the formation of the BCR-ABL1 fusion gene, encoding a constitutively active chimeric tyrosine kinase (TK): BCR-ABL1 that is present in ~3% of pediatric ALL patients with B-immunophenotype and is associated with a poor outcome. This type of ALL is potentially treatable with specific TK inhibitors, such as imatinib. Recent studies have demonstrated the existence of a subset of BCR-ABL1 like leukemias (~10-15% of Bimmunophenotype ALL), whose blast cells have a gene expression profile similar to that of BCR-ABL1 despite the absence of t(9;22)(q34;q11.2). The precise pathogenesis of BCR-ABL1 like ALL is still to be defined, but they are mainly characterized by the activation of constitutive signal transduction pathways due to chimeric TKs different from BCR-ABL1. BCR-ABL1 like ALL patients represent a group with unfavorable outcome and are not identified by current risk criteria. In this review, we will discuss the design of targeted therapy for patients with BCR-ABL1 like ALL, which could consider TK inhibitors, and discuss innovative approaches suitable to identify the presence of patient’s specific chimeric TK fusion genes, such as targeted locus amplification or proteomic biosensors.

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