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Harnessing the Immune System: Current and Emerging Immunotherapy Strategies for Pediatric Acute Lymphoblastic Leukemia

Glasser, Chana L.; Chen, Jing
Treatment for relapsed acute lymphoblastic leukemia (ALL) in children and young adults continues to evolve. Despite optimization of cytotoxic chemotherapeutic approaches and risk-adapted therapy, about 12% of pediatric patients still relapse, and survival rates in this population remain poor. Salvage therapy for relapsed patients continues to be challenging as attempts to further intensify chemotherapy have resulted in excessive toxicity without improving outcomes. Immunotherapy has profoundly impacted the landscape of relapsed ALL by harnessing the patient"™s immune system to target and eliminate leukemia cells. In this review, we provide an overview and summary of immunotherapy agents that have been approved and remain under investigation for children, including blinatumomab, inotuzumab, daratumomab, and chimeric antigen receptor T-cell therapy. We discuss the landmark clinical trials that have revolutionized the field and provide an update on ongoing clinical trials involving these agents for children in the relapsed and upfront setting. The incorporation of these novel immunotherapies into ALL treatment, either as monotherapy or in combination with cytotoxic chemotherapy, has demonstrated promising potential to augment outcomes while decreasing toxicity. However, we also highlight the many challenges we still face and the research critically needed to achieve our goals for cure in children.
ISSN: 2227-9059
CID: 5615112

Early Diagnosis of B-Acute Lymphoblastic Leukemia in a Child Masquerading as Osteomyelitis

Zelaya, Hector M; Picache, Dyana; Ward, Nicholas D; Yan, Zengmin; Glasser, Chana L
PMID: 37337644
ISSN: 1938-2707
CID: 5542582

Concurrent Hepatoblastoma and Wilms Tumor Leading to Diagnosis of Beckwith-Wiedemann Syndrome

Wolfe, Danielle M; Webster Carrion, Andrea; Masukhani, Mahesh M; Oberg, Jennifer A; Pavisic, Jovana; El-Ali, Alexander; Gupta, Mala; Weng, Katherine; Glasser, Chana L
Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4. BWS should be considered in children with atypical presentations of embryonal tumors regardless of clinical phenotype. Risk of malignancy correlates with specific molecular subgroups of BWS making molecular subclassification important for appropriate cancer screening. We report the first case of concurrent embryonal tumors in a phenotypically normal child, leading to the diagnosis of BWS with paternal uniparental disomy and describe the molecular classification of BWS as it relates to malignancy risk, along with approach to management.
PMID: 36730589
ISSN: 1536-3678
CID: 5420412

IL-10 and TNFα are associated with decreased survival in low-risk pediatric acute myeloid leukemia; a children's oncology group report

Stevens, Alexandra M; Horton, Terzah M; Glasser, Chana L; Gerbing, Robert B; Aplenc, Richard; Alonzo, Todd A; Redell, Michele S
Pediatric acute myeloid leukemia (AML) is a devastating disease with a high risk of relapse. Current risk classification designates patients as high or low risk (LR) based on molecular features and therapy response. However, 30% of LR patients still suffer relapse, indicating a need for improvement in risk stratification. Cytokine levels, such as IL-6 and IL-10, have been shown to be prognostic in adult AML but have not been well studied in children. Previously, we reported elevated IL-6 levels in pediatric AML bone marrow to be associated with inferior prognosis. Here, we expanded our investigation to assess cytokine levels in diagnostic peripheral blood plasma (PBP) of pediatric AML patients and determined correlation with outcome. Diagnostic PBP was obtained from 80 patients with LR AML enrolled on the Children's Oncology Group AAML1031 study and normal PBP from 11 controls. Cytokine levels were measured and correlation with clinical outcome was assessed. IL-6, TNFα, MIP-3a, and IL-1β were significantly higher in AML patients versus controls when corrected by the Bonferroni method. Furthermore, elevated TNFα and IL-10 were significantly associated with inferior outcomes. Our data demonstrate that in diagnostic PBP of LR pediatric AML patients, certain cytokine levels are elevated as compared to healthy controls and that elevated TNFα and IL-10 are associated with inferior outcomes, supporting the idea that an abnormal inflammatory state may predict poor outcomes. Studies are needed to determine the mechanisms by which these cytokines impact survival, and to further evaluate their use as prognostic biomarkers in pediatric AML.
PMID: 35838057
ISSN: 1521-0669
CID: 5269422


Jasinski, Sylwia; Monteleone, Berrin; El-Ali, Alexander; Glasser, Chana
ISSN: 1545-5009
CID: 5243892


Glasser, Chana; Joshi, Vivek; Gupta, Mala; Manukyan, Irena; Mansukhani, Mahesh; Subramaniyam, Shivakumar
ISSN: 1545-5009
CID: 5243902

Suspected Case of Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection Presenting as Acute Pancreatitis in a Child With Leukemia [Case Report]

Goldstein, Rebecca; Kogan, Diana; Fiorito, Theresa M; Glasser, Chana L
Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 may present with fever, elevated inflammatory markers, and multiorgan involvement. Although the gastrointestinal system is commonly affected in MIS-C patients, associated necrotizing pancreatitis is rare. We present an 11-year-old boy with B-cell acute lymphoblastic leukemia in remission undergoing maintenance chemotherapy presenting with acute necrotizing pancreatitis. He developed fevers, fluid and electrolyte imbalance, respiratory distress, cytopenias, and coagulopathy, and was found to have markedly elevated inflammatory markers and positive SARS-CoV-2 antibodies. The patient met criteria for MIS-C and was treated with intravenous immunoglobulin with significant clinical improvement. This is the first known reported case of a child with B-cell acute lymphoblastic leukemia who met criteria for MIS-C presenting as acute pancreatitis, and highlights the importance of considering a broader differential for pancreatitis in children given the current SARS-CoV-2 pandemic.
PMID: 34803353
ISSN: 1056-9103
CID: 5063232

Seasonal variation of respiratory viral infections: a comparative study between children with cancer undergoing chemotherapy and children without cancer

Dror, Tal; Akerman, Meredith; Noor, Asif; Weinblatt, Mark E; Islam, Shahidul; Glasser, Chana L
Respiratory viral infections (RVIs) affect children year-round, with seasonal-specific patterns. Pediatric oncology patients are uniquely vulnerable to infection, but whether this predisposes them to different patterns of RVIs than healthy children is unknown. There is also limited data on the impact of RVIs on cancer patients. We conducted a retrospective study of children ages 1-21 with cancer presenting to the clinic and emergency department (ED) and a randomly selected subset of patients without cancer presenting to the ED who had positive nasopharyngeal viral polymerase chain reactions at our institution from 2014 to 2019. Sixty-seven cancer patients (206 RVI episodes) and 225 pediatric non-cancer patients (237 RVI episodes) were included. Human rhino/enterovirus (HRE) was the most common infection in both groups in the spring, summer, and fall. In the winter, the most common RVI was influenza in cancer patients verses respiratory syncytial virus in non-cancer patients. On age-adjusted analysis, the likelihood of detecting coronavirus in the winter, HRE in the spring and fall, and parainfluenza in the summer was significantly greater in cancer patients (OR = 2.60, 2.52, 5.73, 3.59 respectively). Among cancer RVI episodes, 50% received parenteral antibiotics, 22% were severely neutropenic, 22% had chemotherapy delays for a median of six days, 16% were hospitalized, and 6% received intravenous immunoglobulin. We conclude that there are differences in the seasonal patterns of RVIs between children with and without cancer. RVIs also cause significant morbidity in children with cancer.
PMID: 33792490
ISSN: 1521-0669
CID: 4830992

Outpatient supportive care for pediatric acute myeloid leukemia: a single institution's experience

Potashner, Renee; Weinblatt, Mark E; Glasser, Chana L
Infections are responsible for most treatment-related morbidity and mortality in pediatric acute myeloid leukemia (AML). Children's Oncology Group (COG) recommends hospitalization following chemotherapy until early absolute neutrophil count (ANC) recovery. No standard guidelines exist for antibiotic prophylaxis and discharge practices vary. Our objective was to report our institution's experience with outpatient supportive care management following early discharge. A retrospective chart review of pediatric AML patients treated at our institution from 2010 to 2019 was conducted. Data was collected on length of hospitalization, antibiotics administered, infections, and neutropenia duration. Seventeen patients underwent 60 chemotherapy cycles. All were discharged after completion of chemotherapy if clinically stable. Patients were re-admitted for fever and discharged on empiric antibiotics if afebrile with negative cultures. Prophylactic antibiotics were administered in 55 cycles. There were 12 infections in 11 patients and no deaths due to infection. Patients remained outpatient for a mean of 15.8 neutropenia days per cycle. Outpatient supportive care for children with AML may be feasible and safe. Further studies are needed to establish outpatient supportive care guidelines.
PMID: 33792501
ISSN: 1521-0669
CID: 4831002

Characterization of COVID-19 disease in pediatric oncology patients: The New York-New Jersey regional experience

Madhusoodhan, P Pallavi; Pierro, Joanna; Musante, Jordan; Kothari, Prachi; Gampel, Bradley; Appel, Burton; Levy, Adam; Tal, Adit; Hogan, Laura; Sharma, Archana; Feinberg, Shari; Kahn, Alissa; Pinchinat, Ashley; Bhatla, Teena; Glasser, Chana L; Satwani, Prakash; Raetz, Elizabeth A; Onel, Kenan; Carroll, William L
PURPOSE/OBJECTIVE: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. PATIENTS AND METHODS/METHODS:This multicenter, retrospective study included 13 institutions. Clinical and laboratory information on 98 patients ≤21 years of age receiving active anticancer therapy, who tested positive for SARS-CoV-2 by nasopharyngeal swab polymerase chain reaction (PCR), was collected. RESULTS:Of the 578 pediatric oncology patients tested for COVID-19, 98 were positive, of whom 73 were symptomatic. Most experienced mild disease, 28 required inpatient management, 25 needed oxygen support, and seven required mechanical ventilation. There is a slightly higher risk of severe disease in males and obese patients, though not statistically significant. Persistent lymphopenia was noted in severe cases. Delays in cancer therapy occurred in 67% of SARS-CoV-2-positive patients. Of four deaths, none were solely attributable to COVID-19. The impact of the pandemic on pediatric oncology care was significant, with 54% of institutions reporting delays in chemotherapy, 46% delays in surgery, and 30% delays in transplant. CONCLUSION/CONCLUSIONS:In this large multi-institutional cohort, we observed that mortality and morbidity from COVID-19 amongst pediatric oncology patients were low overall, but higher than reported in general pediatrics. Certain subgroups might be at higher risk of severe disease. Delays in cancer care due to SARS-CoV-2 remain a concern.
PMID: 33338306
ISSN: 1545-5017
CID: 4718302