Purpose: Pediatric oncology patients undergoing active chemotherapy are suspected to be at a high risk for severe disease secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection; however, data to support this are lacking. We aim to describe the characteristics of coronavirus disease 2019 (COVID-19) in this population and also its impact on pediatric cancer care in the New York region during the peak of the pandemic.

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Patients: Four hundred seventeen outpatients 55 years and older newly taking any of the 10 most commonly prescribed AEDs between 2000 and 2005.Main Outcome Measure: The percentage of patients who remained taking the AED for 12 or more months (12-month "retention"). We also measured efficacy (12month seizure freedom) and adverse effects leading to dose change. Retention and seizure-freedom rates were analyzed by pairwise comparisons using 2 for the overall group and patients with refractory and nonrefractory disease as well as patients newly taking their first AED. Results:The 10 AEDs newly taken by 10 or more patients were analyzed. There were no significant non-AED predictors of retention. Without controlling for se-verity, lamotrigine had the highest 12-month retention rate (79%), significantly higher than carbamazepine (48%), gabapentin (59%), oxcarbazepine (24%), phenytoin (59%), and topiramate (56%). The retention rate for levetiracetam (73%) was second highest and significantly higher than carbamazepine and oxcarbazepine. Oxcarbazepine had the lowest retention rate, significantly lower than all other AEDs. Lamotrigine had the highest 12-month seizure-freedom rate (54%), followed by levetiracetam (43%). When stratified into patients with nonrefractory and refractory disease, relative rates of seizure freedom and retention remained comparable with the overall group. Imbalance, drowsiness, and gastrointestinal symptoms were the most common intolerable adverse effects. Conclusion:In this study of older adults with epilepsy, lamotrigine was the most effective AED as measured by 12-month retention and seizure freedom, with levetiracetam a close second. Oxcarbazepine was consistently less effective than most other AEDs.

Clinicians can anticipate risk factors for formula use in mothers who plan to breastfeed and tailor counseling appropriately to increase EBF rates.

Introduction The improvement in outcomes for children with acute lymphoblastic leukemia (ALL) is one of the greatest success stories of modern oncology however the prognosis for patients who relapse remains dismal. Recent discoveries by high resolution genomic technologies have characterized the biology of relapsed leukemia, most notably pathways leading to the drug resistant phenotype. These observations open the possibility of targeting such pathways to prevent and/or treat relapse. Likewise, early experiences with new immunotherapeutic approaches have shown great promise. Areas Covered We performed a literature search on PubMed and recent meeting abstracts using the keywords below. We focus on the biology and clonal evolution of relapsed disease and highlight potential new targets of therapy. We further summarize the results of early trials of the three most prominent immunotherapy agents currently under investigation. Expert Commentary Discovery of targetable pathways that lead to drug resistance and recent breakthroughs in immunotherapy show great promise towards treating this aggressive disease. The best way to treat relapse, however, is to prevent it which makes incorporation of these new approaches into frontline therapy the best approach. Challenges remain to balance efficacy with toxicity and to prevent the emergence of resistant subclones which is why combining these newer agents with conventional chemotherapy will likely become standard of care.

The NSD2 p.E1099K (EK) mutation is observed in 10% of acute lymphoblastic leukemia (ALL) samples with enrichment at relapse indicating a role in clonal evolution and drug resistance. To discover mechanisms that mediate clonal expansion, we engineered B-ALL cell lines (Reh, 697) to overexpress wildtype (WT) and EK NSD2, but observed no differences in proliferation, clonal growth, or chemosensitivity. To address whether NSD2 EK acts collaboratively with other pathways, we used shRNAs to knockdown expression of NSD2 in B-ALL cell lines heterozygous for NSD2 EK (RS4;11, RCH-ACV, SEM). Knockdown resulted in decreased proliferation in all lines, decreased clonal growth in RCH-ACV, and increased sensitivity to cytotoxic chemotherapeutic agents, although the pattern of drug sensitivity varied among cell lines implying that the oncogenic properties of NSD2 mutations are likely cell context specific and rely on cooperative pathways. Knockdown of both Type II and REIIBP EK isoforms had a greater impact than knockdown of Type II alone, suggesting that both SET containing EK isoforms contribute to phenotypic changes driving relapse. Furthermore, in vivo models using both cell lines and patient samples revealed dramatically enhanced proliferation of NSD2 EK compared to WT and reduced sensitivity to 6-mercaptopurine in the relapse sample relative to diagnosis. Finally, EK-mediated changes in chromatin state and transcriptional output differed dramatically among cell lines further supporting a cell context specific role of NSD2 EK. These results demonstrate a unique role of NSD2 EK in mediating clonal fitness through pleiotropic mechanisms dependent on the genetic and epigenetic landscape. IMPLICATIONSNSD2 p.E1099K mutation leads to drug resistance and a clonal advantage in childhood B-ALL.

Leukemia, most commonly B-cell acute lymphoblastic leukemia (B-ALL), accounts for about 30% of childhood cancer diagnoses. While there have been dramatic improvements in childhood ALL outcomes, certain subgroups-particularly those who relapse-fare poorly. In addition, cure is associated with significant short-and long-term side effects. Given these challenges, there is great interest in novel, targeted approaches to therapy. A number of new immunotherapeutic agents have proven to be efficacious in relapsed or refractory disease and are now being investigated in frontline treatment regimens. Blinatumomab (a bispecific T-cell engager that targets cluster of differentiation [CD]-19) and inotuzumab ozogamicin (a humanized antibody-drug conjugate to CD22) have shown the most promise. Chimeric antigen receptor T (CAR-T) cells, a form of adoptive immunotherapy, rely on the transfer of genetically modified effector T cells that have the potential to persist in vivo for years, providing ongoing long-term disease control. In this article, we discuss the clinical biology and treatment of B-ALL with an emphasis on the role of immunotherapy in overcoming the challenges of conventional cytotoxic therapy. As immunotherapy continues to move into the frontline of pediatric B-ALL therapy, we also discuss strategies to address unique side effects associated with these agents and efforts to overcome mechanisms of resistance to immunotherapy.