Publications by authors named "Silverman L"

Background: Venous thromboembolism (VTE) is a frequent complication of childhood acute lymphoblastic leukemia (ALL).

Objectives: We aimed to identify molecular markers and signatures of leukemia microenvironment associated with VTE in childhood ALL, by dual-omics approach of gene expression (GEP) and DNA-methylation profiling.

Patients/methods: Eligible children were aged 1-21 years old with newly diagnosed ALL enrolled on the Dana Farber Cancer Institute 16-001 trial with available RNA sequencing data from bone marrow at diagnosis.

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Treatment of acute lymphoblastic leukemia (ALL) is associated with neurocognitive deficits in young children. While computerized measures have been utilized in pediatric oncology research, they exclude patients below the age of 4 years. Patients enrolled on "Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents" were offered participation in an optional neurocognitive study.

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  • Weekly injections for treating growth deficiency in children are just as effective as daily injections, showing similar growth rates.
  • The safety of weekly injections is comparable to daily injections, indicating no significant risk differences.
  • It's important to note that treatment decisions should consider all evidence, not just one study, and approval for the drug may vary by country.
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  • - Asparaginase-containing regimens for acute lymphoblastic leukemia (ALL) result in a significant prevalence of venous thromboembolism (VTE) among adolescents and young adults, with 1-year and 2-year cumulative incidences of 31.9% and 33.5%, respectively, particularly during the ASP-based consolidation phase.
  • - The study revealed that overweight or obese patients had a higher risk of developing VTE (39.2%) compared to those with a normal BMI (29.0%), and overall survival rates were similar regardless of VTE occurrence, at around 91.5%.
  • - Despite the frequent occurrence of VTE, especially types like pulmonary embolism and deep vein thrombosis,
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  • * The study reveals that RAS mutations transform specific blood cell progenitors (granulocyte-monocyte progenitors) that have already acquired other mutations, suggesting advanced leukemia can arise from different cell types than initial clones.
  • * RAS-mutant leukemia stem cells show resistance to the treatment drug venetoclax due to changes in gene expression, leading to worse treatment responses and relapses characterized by monocytic features, highlighting the impact of genetic drivers on therapy effectiveness.
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The Children's Oncology Group study AALL1931 investigated the efficacy and safety of recombinant Erwinia asparaginase (JZP458) in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma and hypersensitivity reactions/silent inactivation to Escherichia coli-derived asparaginases. Each pegylated Escherichia coli asparaginase dose remaining in a patient's treatment plan was replaced by intramuscular (IM) or intravenous (IV) JZP458 (6 doses) administered Monday/Wednesday/Friday (MWF). Three IM cohorts (1a [25 mg/m2 MWF], n=33; 1b [37.

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Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome-wide association study (GWAS) and a transcriptome-wide association study (TWAS) in 260 patients of European-descent from the DFCI 05-001 ALL trial, with validation in 101 patients of European-descent from the DFCI 11-001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05-001 trial (p = 1.

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Poverty-exposed children with cancer are more likely to experience adverse outcomes. Supplemental Nutrition Assistance Program (SNAP) benefits improve food insecurity and child health outcomes, and could be used to mitigate disparities. We conducted a secondary analysis of parent-reported data collected in a frontline pediatric leukemia trial (NCT03020030) to assess SNAP eligibility (proxied by other means-tested program participation) and participation.

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  • - The study aimed to evaluate the effectiveness of combining comparative genomic hybridization and single-nucleotide polymorphism (CGH/SNP) analyses for risk stratification in pediatric acute lymphoblastic leukemia (ALL) compared to traditional cytogenetic methods.
  • - Researchers analyzed data from 135 patients aged 1-18 diagnosed with ALL, finding that CGH/SNP had a significantly lower failure rate and faster result turnaround (5.8 days) than conventional karyotyping (10.7 days).
  • - CGH/SNP detected crucial gene deletions, particularly ETV6, which was associated with better event-free survival, indicating that CGH/SNP could enhance diagnostic accuracy and prognostic evaluation in pediatric ALL.
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A thorough history and physical examination including Tanner staging and growth assessments can guide differential diagnosis and aid in the evaluation of precocious puberty. Basal luteinizing hormone levels measured using a highly sensitive assay can be helpful in diagnosing central precocious puberty (CPP). Brain MRI is indicated with males diagnosed with CPP and females under the age of 6 with CPP.

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Introduction: Studies of gonadotropin-releasing hormone analogues (intramuscular [IM] leuprolide acetate [LA] and triptorelin) for treatment monitoring of central precocious puberty (CPP) demonstrate this approach is effective for confirming pubertal hormone suppression. Herein, we provide new data using subcutaneous LA (SC LA), suggesting similar efficacy for treatment monitoring.

Methods: PubMed, Embase, and CINAHL were searched for studies of GnRHa used to monitor treatment of CPP.

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  • - AYA patients with acute lymphoblastic leukemia (ALL) have poorer treatment completion rates compared to children, with only 60.8% of AYA patients completing their treatment versus 89.7% of children.
  • - The main reason for this discrepancy is the higher incidence of early treatment failure among AYA patients (14.5% vs. 2.4%), while withdrawals due to toxicity or personal issues are less common but still higher in AYA patients (9.3% vs. 4.7%).
  • - Staying on treatment for at least one year significantly improves survival rates, with AYA patients showing 5-year overall survival of 88.9%, but they completed critical asparaginase
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Background: Children treated for acute lymphoblastic leukemia (ALL) receive prolonged treatment, resulting in toxicities that affect health-related quality of life (HR-QoL). Longitudinal assessment of HR-QoL allows improved understanding of experiences with ALL.

Procedure: Parent-proxy and child self-report HR-QoL over the first year of chemotherapy were evaluated in the context of DFCI Protocol 05-001, a phase 3 therapeutic trial for childhood ALL.

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Adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL) treated with asparaginase-containing pediatric regimens are commonly overweight or obese. We studied the association of body mass index (BMI) on outcomes of 388 AYAs aged 15 to 50 years treated on Dana-Farber Cancer Institute (DFCI) consortium regimens (2008-2021). BMI was normal in 207 (53.

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Recognition of aberrant gene isoforms due to DNA events can impact risk stratification and molecular classification of hematolymphoid tumors. In myelodysplastic syndromes, KMT2A partial tandem duplication (PTD) was one of the top adverse predictors in the International Prognostic Scoring System-Molecular study. In B-cell acute lymphoblastic leukemia (B-ALL), ERG isoforms have been proposed as markers of favorable-risk DUX4 rearrangements, whereas deletion-mediated IKZF1 isoforms are associated with adverse prognosis and have been extended to the high-risk IKZF1 signature defined by codeletions, including PAX5.

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Background: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia.

Methods: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study.

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Background: Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001.

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Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP).

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Background: Disparities in COVID-19 information and vaccine access have emerged during the pandemic. Individuals from historically excluded communities (eg, Black and Latin American) experience disproportionately negative health outcomes related to COVID-19. Community gaps in COVID-19 education, social, and health care services (including vaccines) should be prioritized as a critical effort to end the pandemic.

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Purpose: Neurocognitive impairment is frequently observed among survivors of childhood acute lymphoblastic leukemia (ALL) within the domains of attention, working memory, processing speed, executive functioning, and learning and memory. However, few studies have characterized the trajectory of treatment-induced changes in neurocognitive function beginning in the first months of treatment, to test whether early changes predict impairment among survivors. If correct, we hypothesize that those children who are most susceptible to early impairment would be ideal subjects for clinical trials testing interventions designed to protect against treatment-related neurocognitive decline.

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Introduction: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, has a relatively favorable long-term prognosis. Yet the complexity of treatment and the emotionality of the diagnosis leave families feeling unprepared for many aspects of therapy. This qualitative study aimed to identify desired elements and format of a communication resource to support patients and families facing a diagnosis of ALL.

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