National Cancer Institute's Criteria Research Articles

Effectiveness and safety of bortezomib-dexamethasone regimen in patients with multiple myeloma: A prospective observational study

Background: Bortezomib and dexamethasone (BD) regimen offers a promising therapeutic approach in multiple myeloma (MM) by inhibiting the proteolytic pathway of tumor cells. Aims and Objectives: This study aims to assess the safety profile and treatment outcomes of MM patients undergoing the BD regimen. Materials and Methods: This prospective observational study included MM patients who received BD regimen. Patients received bortezomib (1.3 mg/m2 intravenous) weekly for 4 weeks along with dexamethasone (40 mg orally) weekly for 4 weeks. Clinical assessments were performed after each cycle, and adverse drug reactions were graded according to National Cancer Institute criteria. Treatment outcomes were evaluated after the 4th cycle based on specific parameters. Results: Thirty-seven patients, with a mean age of 56.2 years, predominantly male (56.8%), were included. Common symptoms included bone pain, fatigue, weight loss, and appetite loss. Toxicities were mainly grade 1 and 2, with peripheral neuropathy (PN) being the most prevalent. The BD regimen exhibited a response rate of 65%, accompanied by significant improvements in bone marrow plasma cells, β2 microglobulin, immunoglobulin assay, and erythrocyte sedimentation rate. In addition, treatment improved performance status, in 51.4% of patients achieving scores above 90 on the Karnofsky scale. Conclusion: The BD regimen demonstrated notable efficacy and tolerability in MM treatment. However, it is associated with a higher risk of PN.

Prevalence and factors influencing anemia recovery after intensive care

BackgroundAnemia is associated with adverse outcomes and prolonged hospitalizations in critically ill patients. Regarding the recent adoption of restrictive transfusion protocols in intensive care unit (ICU) management, anemia remains highly prevalent even after ICU discharge. This study aimed to investigate the prevalence of anemia following ICU discharge and factors affecting recovery from anemia. MethodsIn this retrospective cohort study involving 3969 adult ICU survivors, we assessed anemia severity using the National Cancer Institute criteria at six time points: ICU admission, ICU discharge, hospital discharge, and at 3-, 6-, and 12-month post-hospital discharge. In addition, baseline characteristics, including age, sex, comorbidities, and recent iron supplementation or erythropoietin administration, were evaluated. ResultsOur findings revealed an in-hospital mortality rate of 28.6%. The median hospital and ICU stays were 20 and 5 days, respectively, with common comorbidities including hypertension, and diabetes mellitus (DM). Among the patients, the hemoglobin levels of 3967 patients were confirmed at the time of discharge from the ICU, representing 99.95% of the total. The prevalence of anemia persisted post- ICU discharge; less than 30% of patients recovered, whereas 13.6% of them experienced worsening of anemia post-ICU discharge. Factors contributing to anemia severity were female sex, DM, chronic renal failure, malignant solid tumors, and administration of iron supplements. ConclusionsThis study highlighted the need for targeted interventions to manage anemia post-ICU discharge and suggested potential factors that influence recovery from anemia.

Biological Markers of High-Risk Childhood Acute Lymphoblastic Leukemia.

Childhood acute lymphoblastic leukemia (ALL) has witnessed substantial improvements in prognosis; however, a subset of patients classified as high-risk continues to face higher rates of relapse and increased mortality. While the National Cancer Institute (NCI) criteria have traditionally guided risk stratification based on initial clinical information, recent advances highlight the pivotal role of biological markers in shaping the prognosis of childhood ALL. This review delves into the emerging understanding of high-risk childhood ALL, focusing on molecular, cytogenetic, and immunophenotypic markers. These markers not only contribute to unraveling the underlying mechanisms of the disease, but also shed light on specific clinical patterns that dictate prognosis. The paradigm shift in treatment strategies, exemplified by the success of tyrosine kinase inhibitors in Philadelphia chromosome-positive leukemia, underscores the importance of recognizing and targeting precise risk factors. Through a comprehensive exploration of high-risk childhood ALL characteristics, this review aims to enhance our comprehension of the disease, offering insights into its molecular landscape and clinical intricacies in the hope of contributing to future targeted and tailored therapies.

Real-world overall survival (OS) of patients (pts) with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic therapy (tx): Results from IMPACT UC II.

529 Background: Urothelial cancer (UC) is the most common urinary system cancer. The IMPACT UC II study aimed to assess tx patterns and clinical outcomes in pts with mUC treated with platinum-based chemotherapy or immuno-oncology monotherapy (IO-mono) in 1L. Methods: This was a retrospective claims analysis of pts diagnosed with mUC from July 2015 to June 2020 and continuously enrolled for 6 mo before and ≥6 mo after index date (ie, date of first claim) using Optum Research Database, which represents ≈8% of commercially insured and 18% of Medicare Advantage (MAPD) populations. Pts were followed up until disenrollment, study end in August 2021, or death. Analyses examined OS and time to 2L tx (TT2L) in three tx cohorts: cisplatin (cis)-based, carboplatin (carbo)-based, or IO-mono. Results: Of 3,006 pts diagnosed with mUC, 1,037 received 1L tx: 365 (35.2%) with cis-based tx; 337 (32.5%) with carbo-based tx, and 335 (32.3%) with IO-mono. Among treated pts, mean age was 72.5 years (SD, 9.9 years), 72.3% were male, and 77.4% were MAPD insured. At baseline, pts receiving cis-based tx had a lower percentage of ≥3 comorbidities (defined by National Cancer Institute criteria): cis-based, 22.2%; carbo-based, 39.5%; and IO-mono, 45.1%. Among 290 pts (27.9%) receiving 2L tx, carbo-based tx had the shortest median TT2L (5.7 mo). Pts receiving cis-based tx had the longest median OS (27.4 mo). Relative to cis-based tx, multivariable–adjusted mortality risk was 2 times higher with IO-mono (hazard ratio [HR], 2.0; 95% CI, 1.6-2.5) and 1.5 times higher with carbo-based tx (HR, 1.5; 95% CI, 1.3-1.9) (Table). Conclusions: This study shows that, before avelumab 1L maintenance approval, the majority of pts did not receive any systemic anticancer tx. following mUC diagnosis. In 1L, after multivariable adjustment (including for baseline comorbidities), real-world OS was lower in pts receiving carbo-based tx and IO-mono compared with cis-based tx. Future research should examine outcomes with newer standard of care.[Table: see text]

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

1120. Descriptive Analysis of Monoclonal Antibody Administration for Pregnant Patients with SARS-CoV-2 Infection

Abstract Background We studied the safety and efficacy of the use of monoclonal antibodies (MAB) against SARS-CoV-2 in pregnant women who developed COVID-19 infection. Methods We conducted a cross-sectional descriptive multi-center study of pregnant patients who developed SARS-CoV-2 infection from January 2021 to January 2022 and received MAB therapy. Primary outcomes assessed were infusion-related adverse events and pregnancy outcomes within one month of MAB infusion. The secondary outcomes assessed were hospitalization and ICU admission for COVID19 infection and thirty-day all-cause mortality. Results 141 patients were included in the study (median age 33 +/- 5.3 SD, median BMI 28.9 +/- 8.42 SD). In terms of COVID vaccination status, 49.6% received one dose, 36.1% were fully vaccinated, and 7% received the booster dose. Most patients received casirivimab/imdevimab (105, 74.5%) followed by sotrovimab (33, 23.4%). Four patients developed adverse reactions to MAB infusion (two grade-2 reactions and two grade-1 reactions as per the National cancer institute infusion reaction grading criteria). Only one patient (0.7%) was hospitalized for COVID-19 infection, however, she was not hypoxic nor required ICU admission. Five patients delivered within four weeks of MAB administration, however, four of those patients were of gestational age &amp;gt; 37 weeks. Data for 30-day all-cause mortality was available on 88.7% (125) of the patients and data for 30-day pregnancy adverse outcomes was available on 86.5% (122) of the patients due to lack of follow-up within the Health System. There was no reported 30-Day all-cause mortality within the cohort. Two patients (1.4%) had premature rupture of the membrane and one patient (0.7%) had premature delivery within 30 days of receiving MAB. Two patients had preeclampsia (1.4%) and one patient (0.7%) was admitted for evaluations of decreased fetal movements. Conclusion Administration of monoclonal antibodies against SARS-CoV-2 was well tolerated during pregnancy. Only 4 out of 141 (2.8%) had mild to moderate infusion-related reactions. The 30-day pregnancy adverse outcomes observed were well below the mean background rate. There was no reported mortality among MAB recipients and only one patient was hospitalized for mild COVID19 infection. Disclosures All Authors: No reported disclosures.

Central Nervous System Toxicity of Voriconazole: Risk Factors and Threshold - A Retrospective Cohort Study.

Voriconazole (VRC) is an antifungal agent which is used for treatment and prophylaxis of invasive fungal infections. The common clinical adverse reactions mainly include central nervous system (CNS) toxicity and abnormal liver function. These adverse reactions limit the clinical use of voriconazole to a certain extent. Therefore, the aim of this study was to analyze the risk factors of voriconazole neurotoxic side effects and to determine the plasma trough concentration (C min) threshold of voriconazole-induced CNS toxicity, so as to improve the safety of voriconazole treatment. This study retrospectively collected the clinical data of 165 patients who received voriconazole and underwent therapeutic drug monitoring (TDM). CNS toxicity was defined using the National Cancer Institute (NCI) criteria, logistic regression was used to analyze the risk factors of CNS toxicity, classification and Regression tree (CART) model was used to determine the C min threshold for CNS toxicity. Voriconazole-related CNS toxicity occurred during treatment in 34 of 165 patients (20.6%) and the median time from administration to onset of CNS toxicity was 6 days (range, 2-19 days). The overall incidence of CNS toxicity was 20.6% (34/165), including visual disturbances in 4.8% (8/165) and nervous system disorders in 15.8% (26/165). C min significantly affects the occurrence of CNS toxicity and the threshold of C min for voriconazole CNS toxicity was determined to be 4.85 mg/L, when C min >4.85 mg/L and ≤4.85 mg/L, the incidence of CNS was 32.9% and 11.6%, respectively. Voriconazole trough concentration of C min is an independent risk factor for CNS toxicity, and the threshold of C min for CNS toxicity is 4.85mg/L. TDM should be routinely performed in patients with clinical use of voriconazole to reduce the occurrence of CNS toxicity of voriconazole.

Addressing Health Disparities Across the Cancer Continuum-a Los Angeles Approach to Achieving Equity.

IntroductionDifferent models have been developed to address inequities across the cancer care continuum. However, there remains a scarcity of best practices on understanding and responding to the burden of cancer in a defined catchment area.As such, the National Cancer Institute (NCI) recently provided a framework to maximize the impact on cancer burden, including a greater focus on community outreach and engagement. In this paper, we describe how Cedars Sinai Cancer (CSC), a health system that serves one of the most diverse counties in the US, implemented the framework to define its catchment area, characterize its population, identify high risk priority groups, and make decisions to address health disparities.MethodsWe provide a review of the methods used to assess socio-ecological levels of influence. Data were reviewed from numerous national, statewide, and county sources and supplemented by locally administered questionnaires, heat maps, and community profile summaries to gain more localized snapshots of cancer disparities in Los Angeles County. Lastly, feedback was solicited from external peer groups, community stakeholders, and key decision-makers, and the proposed catchment area was aligned with the State’s Cancer Plan and the NCI Catchment Area and Community Outreach and Engagement Mandate.ResultsThe selected CSC catchment area meets NCI criteria and has potential to demonstrate impact both at the population level and within specialty populations. As a result, strategies are being developed to organize community outreach and engagement, as well as research across basic, clinical, and population sciences to guide cancer control and prevention efforts.DiscussionTo maintain a high level of cultural inclusion and sensitivity, multiple layers of data are needed to understand localized pictures of cancer disparities and underlying causes. Community engagement remains essential to implementing policy, best practice, and translational science for broader impact.ImpactThe clinical and translation work conducted at any cancer center requires an understanding of the determinants of health that contribute to the differences in cancer incidence and mortality among different groups. The NCI-aligned approach that we highlight is critical to support the design of future cancer control strategies that address and possibly reduce local health inequities.

Alterations in Bone Turnover during Chemotherapy in Children with Acute Lymphoblastic Leukemia.

Background Disturbances of bone metabolism frequently occur in children with acute lymphoblastic leukemia (ALL), leading to increased risk of osteopenia and osteoporosis at diagnosis, during and after completion of chemotherapy. The present study was performed to evaluate alteration in bone mineral metabolism in children with ALL during chemotherapy. Method Fifty newly diagnosed patients with ALL in the age group of 2 to 14 years were included. Relapsed and refractory cases were excluded. Enrolled children were stratified into standard and high risk according to National Cancer Institute criteria. Quantitative analysis of bone resorptive marker carboxyl-terminal telopeptide of human type 1 collagen (ICTP) was assessed at baseline and 3 months after chemotherapy by the sandwich enzyme-linked immunosorbent assay technique. Results Of 50 patients enrolled, 21 were standard and 29 were high risk. The mean age was 7.75 ± 4.0 years and the male-to-female ratio was 3.5:1. ICTP levels were analyzed in 44 patients, of which 37 (84%) showed significantly increased levels. The mean ICTP level in patients at diagnosis and controls was 1.78 ± 1.39 and 0.96 ± 0.32 µg/L, respectively ( p = 0.001). The mean ICTP level at 3 months after chemotherapy increased to 3.55 ± 1.40 µg/L ( p = 0.000). It was significantly increased in males ( p = 0.000) and in B cell ALL group ( p = 0.000) in comparison to females and T cell group. Both standard and high risk groups were equally affected ( p = 0.000). On multivariate analysis, no single risk factor could be identified. Conclusion The marker of bone resorption (ICTP) in children with ALL was increased at diagnosis, which further increased during chemotherapy. The disease itself and the intensive chemotherapy both contributed to the increased levels.

Genetic Alterations in Childhood Acute Lymphoblastic Leukemia: Interactions with Clinical Features and Treatment Response.

Simple SummaryThe latest molecular taxonomy of acute lymphoblastic leukemia (ALL) comprises >20 distinct genetic subtypes, each with their own unique clinical and prognostic characteristics. In this review, we describe how these new genetic subtypes interact with clinical presenting features, IKZF1del, treatment response, and outcomes, which is helpful for clinical use.Acute lymphoblastic leukemia (ALL) is the most common cancer among children. This aggressive cancer comprises multiple molecular subtypes, each harboring a distinct constellation of somatic, and to a lesser extent, inherited genetic alterations. With recent advances in genomic analyses such as next-generation sequencing techniques, we can now clearly identify >20 different genetic subtypes in ALL. Clinically, identifying these genetic subtypes will better refine risk stratification and determine the optimal intensity of therapy for each patient. Underpinning each genetic subtype are unique clinical and therapeutic characteristics, such as age and presenting white blood cell (WBC) count. More importantly, within each genetic subtype, there is much less variability in treatment response and survival outcomes compared with current risk factors such as National Cancer Institute (NCI) criteria. We review how this new taxonomy of genetic subtypes in childhood ALL interacts with clinical risk factors used widely, i.e., age, presenting WBC, IKZF1del, treatment response, and outcomes.

Abstract No. 525 Yttrium-90 radioembolization of segment IV hepatocellular carcinoma: assessment of biliary complications in a region dense with biliary structures

Biliary complications are a known risk from Yttrium-90 radioembolization of hepatocellular carcinoma (HCC). The proposed mechanism of injury is due to microembolic effect and/or radiation-induced injury to the biliary system1. We investigate whether lesions treated in segment IV demonstrated a higher incidence of biliary complications compared to the literature due to the higher density of biliary structures within this segment. A single-institution retrospective analysis of patients with segment IV HCC treated with Yttrium-90 microspheres from 2013 to 2019. Inclusion criteria included: diagnosis of HCC to segment IV, at least one follow-up computed tomography or magnetic resonance examination within 90 days of treatment, and serum total bilirubin before and within 90 days post treatment. Exclusion criteria included liver transplantation. Thirty patients met criteria with an average length of follow-up imaging at 46 days. Biliary complications included, but were not limited to: biloma, cholecystitis, biliary strictures, and grade 3 or 4 biliary toxicity by National Cancer Institute criteria. Of 30 patients, one patient was found to have multifocal biliary strictures requiring two biliary stents on endoscopic retrograde cholangiopancreatography five months post procedure (n = 1, 3.3%). Two patients demonstrated grade 3/4 bilirubin toxicity (n = 2, 6.7%). The average treatment dosage was 135 Gray (range, 95–341 Gy). Compared to the biliary complication rate described in the literature for HCC with 2.1% for biliary findings on imaging and 6.8% for grade 3/4 bilirubin toxicity2, our study showed comparable rates of 3.3% and 6.7%, respectively. Yttrium-90 radioembolization of segment IV HCC demonstrated no significant difference in biliary complication rates compared to nonsegment specific biliary complication rates reported in the literature.

Contribution of Polygenic Risk to Hypertension Among Long-Term Survivors of Childhood Cancer

BackgroundChildhood cancer survivors experience significantly higher rates of hypertension, which potentiates cardiovascular disease, but the contribution and relationship of genetic and treatment factors to hypertension risk are unknown. ObjectivesThis study sought to determine the contribution of a blood pressure polygenic risk score (PRS) from the general population and its interplay with cancer therapies to hypertension in childhood cancer survivors. MethodsUsing 895 established blood pressure loci from the general population, we calculated a PRS for 3,572 childhood cancer survivors of European ancestry from the Childhood Cancer Survivor Study (CCSS) original cohort, 1,889 from the CCSS expansion cohort, and 2,534 from the St. Jude Lifetime Cohort. Hypertension was assessed using National Cancer Institute criteria based on self-report of a physician diagnosis in CCSS and based on blood pressure measurement in the St. Jude Lifetime Cohort. ResultsIn the combined sample of 7,995 survivors, those in the top decile of the PRS had an odds ratio (OR) of 2.66 (95% confidence interval [CI]: 2.03 to 3.48) for hypertension compared with survivors in the bottom decile. The PRS-hypertension association was modified by being overweight/obese (per standard deviation interaction OR: 1.13; 95% CI: 1.01 to 1.27) and exposure to hypothalamic-pituitary axis radiation (per standard deviation interaction OR: 1.18; 95% CI: 1.05 to 1.33). Attributable fractions for hypertension to the PRS and cancer therapies were 21.0% and 15.7%, respectively; they jointly accounted for 40.2% of hypertension among survivors. ConclusionsA blood pressure PRS from the general population is significantly associated with hypertension among childhood cancer survivors and contributes to approximately one quarter of hypertension risk among survivors. These findings highlight the importance of screening for hypertension in all childhood cancer survivors and identifying higher-risk subgroups.

Mecobalamin as a Neuroprotective Effector against Oxaliplatin-Based Chemotherapy in Colon and Rectal Cancer Patients

Palliative chemotherapy prolongs survival and improves quality of life. However, a variety of chemotherapeutics including oxaliplatin can cause severe side effects during treatments, leading to painful symptoms that might result in the interruption of cancer treatment. Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon and rectal cancer may improve disease-free survival, it also increases grade 3–4 sensory neuropathy. Our study aimed to determine whether oral Mecobalamin is neuroprotective against oxaliplatin-induced neuropathy. Forty-six stage III colon and rectal cancer patients receiving adjuvant biweekly oxaliplatin were randomized to oral Mecobalamin (1,500 mg; case group) or placebo (control group). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) criteria. After four cycles of chemotherapy, 9 of 23 patients in the control group and 8 of 23 patients in case group experienced grade 1 sensory neuropathy. After eight cycles, 13 patients experienced sensory neuropathy (grade 2–4 toxicity) in the control group; however, no patients in the case group experienced sensory neuropathy (P &lt; 0.05). After 12 cycles, grade 2–4 sensory neuropathy was observed in 20 patients in the control group, but only in 4 patients in the case group (P &lt; 0.05). We did not observe any significant electrophysiological changes in the case group after 4, 8, or 12 cycles of chemotherapy. Thus, we demonstrated that oral Mecobalamin reduces the incidence of neuropathy in colon and rectal cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

Cytotoxicity of ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) on HeLa cell line

In our previous study, some amino chalcone derivatives have been synthesized and evaluated their cytotoxicity against breast cancer cell line T47D. Among 11 amino chalcone derivatives, ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) exhibited the most active compound.This study aimed to investigate cytotoxic activity of the ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) against cervical cell line (HeLa). The cytotoxic activitywas determined using the MTT colorimetric assay. Cisplatin was used as positive control. From this MTT method, inhibitory concentration 50% (IC50) values were determined by probit analysis based on the relationship between log concentrations versus the percentage of cells growth inhibition.The results showed that the IC50 of ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) and cisplatinwere 22.75 ± 19.13 μg/mL and 14.96±1.08 μg/mL, respectively. In conclusion, the ((E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one)) has moderate cytotoxic activity against HeLa cell line based on National Cancer Institute (NCI) criteria.

A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia

AbstractPreclinical studies with the histone deacetylase (HDAC) inhibitor depsipeptide (FK228) in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) have demonstrated that it effectively induces apoptosis at concentrations at which HDAC inhibition occurs. We initiated a minimum effective pharmacologic dose study of depsipeptide, targeting an in vivo dose at which acetylation of histone proteins H3 and H4 increased by 100% or more in vitro. Ten patients with CLL and 10 patients with AML were treated with 13 mg/m2 depsipeptide intravenously days 1, 8, and 15 of therapy. Neither life-threatening toxicities nor cardiac toxicities were noted, although the majority of patients experienced progressive fatigue, nausea, and other constitutional symptoms that prevented repeated dosing. Several patients had evidence of antitumor activity following treatment, but no partial or complete responses were noted by National Cancer Institute criteria. HDAC inhibition and histone acetylation increases of at least 100% were noted, as well as increases in p21 promoter H4 acetylation, p21 protein, and 1D10 antigen expression. We conclude that depsipeptide effectively inhibits HDAC in vivo in patients with CLL and AML, but its use in the current schedule of administration is limited by progressive constitutional symptoms. Future studies with depsipeptide should examine alternative administration schedules.

Anti-Tumor Effect of Green Tea Extract, Simvastatin and Gamma Radiation on Solid Tumor in Mice

The current study was conducted of six groups (n=12) to define the efficacy of epigallocatechin gallate, simvastatin and gamma radiation individually or combined together to reduce solid tumor size induced by intramuscular injection of EC cells in the right thigh of the targeted mice. Magnetic resonance imaging device 1.5 Tesla used for radiology imaging of the normal and ascites-bearing mice under anesthesia. The animals with solid tumor were followed up daily for recording deaths, tumor size, rate of inflammation and gangrene in the tumor area of hind limb. Magnetic resonance imaging showed the intraperitoneal ascites and the soft organs (liver, kidney and intestine) which were bright in the case of ascites-bearing mouse than the normal control. Triple therapy regimen significantly reduced the tumor size (662.6±12.5) compared to the positive control (825±21.8) and increased survival rate to 66.7% compared to 25% in the positive control. Triple therapy reduced the inflammation of tumor area, preventing the gangrene incidence, and showed the best value of T/C=142, ILS=42.11 and TIR %=19.6 compared to the positive control and single treatments, so it is considered as an anti-tumor regimen according to the National Cancer Institute criteria.

Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate.

Introduction: High dose methotrexate (HD-Mtx) is highly effective and significantly improves overall acute lymphoblastic leukemia (ALL) patients survival. The pharmacodynamics of Mtx depends on the polymorphism of genes encoding proteins engaged in the folate metabolism pathway. The aim of the current study is to determine the relationship between variants of folate metabolism-related genes and the frequency of acute toxicities of HD-Mtx.Material and Methods: A group of 133 patients aged 1.5–18.1 years (median: 6.3) was treated in accordance with the ALL-IC-2002 and ALL-IC-2009 protocols. The following polymorphisms were determined: 80 G>A SLC19A1 (solute carrier family 19 member 1; rs1051266) with direct DNA sequencing, as well as 677 C>T MTHFR (methylenetetrahydrofolate reductase; rs1801133) and the tandem repeats of the TS (thymidylate synthase) with PCR technique. HD-Mtx organ toxicities were evaluated based on the laboratory tests results and the National Cancer Institute criteria.Results: In patients with genotypes AA for SLC19A1 and CC or CT for MTHFR Mtx steady state concentrations (Css) and AUCinf were distinctly higher. In patients with genotype 3R/3R for TS initial elimination rate constant was significantly higher (P = 0.003). Patients receiving Mtx at the dose of 5 g/m2 had lower clearance (4.35 vs. 8.92 L/h/m2) as compared to the ones receiving 2 g/m2 that indicates non-linear Mtx elimination at the higher dose. Liver impairment was the most frequently observed toxicity. The homozygous genotype was associated with a significantly higher incidence of hepatic toxicity for both the SLC19A1 (P = 0.037) and TS (P = 0.002). Logistic regression analysis indicated an increased risk of vomiting for the 2R/3R genotype of the TS gene (OR 3.20, 95% CI 1.33–7.68, P = 0.009) and for vomiting and hepatic toxicity for the 3R/3R genotype (vomiting: OR 3.39, 95% CI 1.12–10.23, P = 0.031; liver toxicity: OR 2.28, 95% CI 1.05–4.95, P = 0.038). None of the acute toxicities differed between the analyzed dosing groups.Conclusions: Determination of polymorphisms of SLC19A1, MTHFR, and TS genes might allow for a better prior selection of patients with higher risk of elevated Mtx levels. Our study is the first one to report the increased risk of hepatotoxicity and vomiting in patients with TS polymorphisms.

4396 Immunoglobulin administration and hypogammaglobulinemia during pediatric acute leukemia therapy

OBJECTIVES/GOALS: Intravenous immunoglobulin (IVIG) is used for infection prevention in pediatric B-cell acute lymphoblastic leukemia (B-ALL), but evidence for this is lacking. We describe the prevalence of hypogammaglobulinemia in pediatric B-ALL, predictors of IVIG use and its efficacy for infection prevention. METHODS/STUDY POPULATION: We will conduct a retrospective review of children age 1-21 years with B-ALL treated at Aflac Cancer and Blood Disorders Center from 2010 to 2017. The cohort was identified through the cancer registry. Demographics, disease factors, laboratory values, medications and infection outcomes were linked between the electronic medical record and an institutional database. Outcomes of interest include emergency department (ED) visits, hospitalization days, and episodes of infection. Descriptive statistics will be performed. Outcomes will be compared between IVIG recipients and non-recipients. Univariate and multivariate logistic regression models will assess predictors of IVIG administration. RESULTS/ANTICIPATED RESULTS: We identified 443 patients with B-ALL during the study period who met inclusion criteria. Exclusion criteria included receipt of IVIG or hematopoietic stem cell transplant prior to diagnosis. The average age at diagnosis is 6.5 years (standard deviation 4.8 years); 52.6% are male; 61.6% are white; 61.0% are standard risk per National Cancer Institute criteria. Among eligible patients, 137 (31.1%) received IVIG. We hypothesize that IVIG initiation is associated with hypogammaglobulinemia and history of severe infection. We also anticipate that frequency of emergency department visits, hospitalization days, and episodes of infection will decrease after IVIG initiation. DISCUSSION/SIGNIFICANCE OF IMPACT: The immunological profile of children with B-ALL and factors influencing their susceptibility to infection are still incompletely understood. The benefits of IVIG are unknown. This study will provide evidence for IVIG prophylaxis recommendations in pediatric leukemia patients.

Young head and neck cancer patients are at increased risk of developing oral mucositis and trismus.

To evaluate cancer treatment-related toxicities in young head and neck cancer (HNC) patients. A total of 44 patients were included in the present retrospective cohort study, which was designed to access oral toxicities of cancer treatment in young (< 45years of age, Group I, n = 22) and old (> 58years of age, Group II, n = 22) HNC patients with similar tumor stage and treatment protocols. Oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis were assessed during days 7th, 21st, and 35th of head and neck radiotherapy (HNRT) according to previously validated scales (World Health Organization criteria and the National Cancer Institute and Common Terminology Criteria for Adverse Events version 4.0). Patients from both groups showed high incidence and severity of oral toxicities by the end of the HNRT with OM (81.9% (Group I); 63.6% (Group II)) and xerostomia (72.6% (Group I); 77.2% (Group II)) being the most prevalent toxicities. No differences regarding xerostomia, dysphagia, dysgeusia, and radiodermatitis incidences or severity could be observed between groups. However, higher incidences and severity of OM at 21st and 35th fractions (odds ratio = 2.22 and 5.71, respectively) and trismus at 21st and 35th fractions (odds ratio = 6.17 and 14.5, respectively) were observed throughout the treatment in young patients when compared to older patients (p < 0.01 and p < 0.05, respectively). Young HNC patients are more affected by cancer treatment-related OM and trismus despite the similarities in clinical staging and treatment protocols with elderly patients.

Association of Gastrointestinal Chemotoxicity to the Performance Status of Breast Cancer Patients: A Preliminary Study

Abstract Background Chemotherapy is still the first line treatment for breast cancer patients. Gastrointestinal chemotoxicity such as nausea and vomiting remain as distressing adverse side effects. However, not many data discussed the impact of these side effect on the performance status of the patients. Thus, the aim of the study is to evaluate the Association of gastroenteric chemotoxicity to the performance status of Breast cancer patients. Method A cross-sectional study was done in our general hospital starting from October 2018 until February 2019. The patients included are those diagnosed with breast cancer and have undergone chemotherapy. Chemotherapy toxicity is assessed using the National cancer institute common toxicity criteria (NCI-CTC) with a cut-off above 1 point. and Eastern Cooperative Oncology Group (ECOG) was used to assess the patient´s performance status. The ECOG has a scoring system (0-5). Which 0 defines as fully active and 5 as dead. The correlation between both variables was analyzed with spearman using SPSS version 24.0 Result Data are collected from 32 patients with mean age 47.72±9.095. Out of the patients, only 6.2% experienced nausea and vomiting. The performance status data showed 46.9% scored 0, 50% scored 1, and only 3.1% scored 2. The association of these chemotoxicity to the patient´s status performance is less significant with r = 0.223, p-value=0.221 Conclusion Chemotoxicity did not occur in most patient. However patients still tends to have restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. The study resulted in minimum coherence and significance from both variables. Therefore further study with a larger sample size should be done.