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.

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.

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.

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.

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.

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.

Role of Matrix Metalloproteinase MMP-2, MMP-9 and Tissue Inhibitor of Metalloproteinase (TIMP-1) in Clinical Progression of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Maha Saleh ◽  
Mohamed Khalil ◽  
Mona S. Abdellateif ◽  
Emad Ebeid ◽  
Eman Z. Kandeel
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Count ◽  
Cancer Progression ◽  
Lymphoblastic Leukemia ◽  
Multivariate Logistic Regression Analysis ◽  
Blast Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

Abstract Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- CSCs were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, P<0.001], and CSCs CD84+CD38- [1 (0.03-18.6) versus 0.3 (0.01-1.1), P<0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, AUC of MMP-2 were (80.3%, 53.3% and 0.568, P=0.404), and that of MMP-9 were (53.9%, 40% and 0.660, P=0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, P<0.001), and that of CSCs CD34+ CD38- were (78.9%, 73.3% and 0.855, P<0.001). There was a significant association between MMP-2 overexpression and MRD at day-15, increased BM blast cell count at diagnosis and at day-15, (P=0.020, P=0.047 and P=0.001). Increased TIMP-1 expression associated with the high-risk disease (P<0.001), increased BM blast cell count at diagnosis and at day-15 (P=0.033 and P=0.001), as well as MRD at day 15 and day 42 (P<0.001 for both). CD34+CD38- CSCs associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (P=0.015, P=0.005 and P=0.003). TIMP-1 overexpression associated with shorter DFS and OS rates (P=0.009 and P=0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, P=0.046], and CD34+CD38- CSCs [OR: 6.873, P=0.005] are independent diagnostic factors for pediatric ALL.Conclusion: TIMP-1 and CD34+CD38- CSCs could be useful independent diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

scholarly journals “SOCIOECONOMIC FACTORS AFFECTING SURVIVAL IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA FROM NORTH-EAST INDIA”

2020 ◽  
pp. 1-3
Author(s):  
Partha Sarathi Roy ◽  
Munlima Hazarika ◽  
Rakesh Kumar Mishra ◽  
BhargabJyoti Saikia ◽  
Gaurav Kumar
Keyword(s):  
Overall Survival ◽  
Developing Countries ◽  
Acute Lymphoblastic Leukemia ◽  
Socioeconomic Factors ◽  
Lymphoblastic Leukemia ◽  
Childhood All ◽  
Female Ratio ◽  
Risk Of Death ◽  
Lower Socioeconomic ◽  
Pediatric All

Acute lymphoblastic leukemia (ALL) is a highly curable childhood cancer with a survival rate of nearly 80% in developed countries but is around 45% in developing countries. This retrospective study analyzed the association between demographic and socioeconomic factors with survival in pediatric ALL. All confirmed cases of pediatric ALL (age <18 years) registered at Dr. B Borooah Cancer Institute between 2010 to 2017 were analyzed using data collected from hospital-based cancer registry and case records. Seventy-five confirmed cases of pediatrics ALL were eligible for the study. The median age of presentation was six years with a male: female ratio 1.9:1. Overall survival at 4-years was 43.8%, with a median survival of 25 months. A trend for higher 4-year overall survival was seen in female children (54.1% versus 37.9%, p=0.097). Patients from rural areas (44% versus 39.5%, p=0.308), with higher maternal education (83.3% versus 41.1%, p=0.161) and patients who did not abandon treatment (49.1% versus 31.2%, p=0.497) had better survival, but the differences were not significant. Four years overall survival in upper-middle, lower-middle, upper-lower, and lower class were 85.7%, 74.9%, 38.1%, and 7.7% respectively (upper-middleversus lower socioeconomic class, p=0.0001).Multivariate analyses confirmed a statistically significant relationship between socioeconomic status and survival, with the upper-middle group had a 90% decreased risk of death compared to the lower socioeconomic group. There is an urgent need for a proper definition of the problems of childhood ALL to introduce appropriate policies for improving survival in developing countries.

scholarly journals Effects of TPMT, NUDT15, and ITPA Genetic Variants on 6-Mercaptopurine Toxicity for Pediatric Patients With Acute Lymphoblastic Leukemia in Yunnan of China

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoyan Mao ◽  
Runxiu Yin ◽  
Gaoyuan Sun ◽  
Yan Zhou ◽  
Chunhui Yang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Yunnan Province ◽  
Medical Center ◽  
Lymphoblastic Leukemia ◽  
Free Survival ◽  
Ethnic Populations ◽  
Significant Difference ◽  
Pediatric All ◽  
Medical University ◽  
Tolerable Dose

Background: 6-Mercaptopurine (6-MP) is the cornerstone of current antileukemia regimen and contributes greatly to improve the survival of pediatric acute lymphoblastic leukemia (ALL) patients. However, 6-MP dose-related toxicities limit its application. TPMT, NUDT15, and ITPA are pharmacogenetic markers predicting 6-MP-related toxicities, but their genetic polymorphisms differ from those of ethnic populations. In Yunnan province, a multiethnic region of China, we had no genetic data to predict 6-MP toxicities. In this study, we evaluated the most common variants involved in 6-MP metabolism—TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) variants—in our cohort of pediatric ALL patients.Methods: A total of 149 pediatric ALL patients in the Affiliated Children's Hospital of Kunming Medical University (Yunnan Children's Medical Center) from 2017 to 2019 were enrolled in this retrospective study. We assessed the TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) frequencies and evaluated association between genotypes and 6-MP toxicities, 6-MP dose, and event-free survival (EFS) in these ALL patients.Results: The allele frequencies of TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) were 1.34%, 14.43%, and 18.79%, respectively. Only NUDT15 c.415C&gt;T (rs116855232) was strongly associated with 6-MP toxicity and 6-MP tolerable dose. NUDT15 c.415C&gt;T was related to leukopenia, p = 0.008, OR = 2.743 (95% CI: 1.305–5.768). The T allele was significantly correlated with 6-MP tolerable dose, dose of NUDT15 c.415C&gt;T wild genotype CC 39.80 ± 1.32 mg/m2, heterozygotes CT 35.20 ± 2.29 mg/m2, and homozygotes TT 18.95 ± 3.95 mg/m2. 6-MP tolerable dose between CC and TT had a significant difference, p = 0.009. Between CC and CT, and CT and TT, they had no significant difference. EFS showed no significant difference among NUDT15 c.415C&gt;T genotypes.Conclusion:NUDT15 c.415C&gt;T (rs116855232) was an optimal predictor for 6-MP toxicity and tolerable dose in pediatric ALL patients from Yunnan province, a multiethnic region in China, and would play an important role in precise therapy for ALL.

scholarly journals Emerging Pharmacotherapies for Adult Patients with Acute Lymphoblastic Leukemia

2012 ◽  
Vol 6 ◽  
pp. CMO.S7262 ◽  
Author(s):  
Lydia Lee ◽  
Adele K. Fielding
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Sustained Remission ◽  
The Novel ◽  
Durable Response ◽  
Treatment Regimes ◽  
The Face ◽  
Pediatric All ◽  
Relapsed Disease ◽  
Failure Of Induction

Acute lymphoblastic leukemia (ALL) treatment regimes are amongst the longest, most intensive and complex used in hemato-oncology. Despite this, while treatment of pediatric ALL is a success story, we are far from being able to ensure a durable response in adult ALL. This is not due to failure of induction therapy as a complete remission (CR) is achieved in over 90% of patients. However the challenge remains in ensuring a sustained remission. Furthermore in the face of relapsed disease, salvage therapies currently offer a poor chance of a good outcome. This article reviews the novel agents which show the most promise in the treatment of adult ALL.

Sign in / Sign up

Export Citation Format

Share Document