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Ami V Desai
Department of Pediatrics, The University of Chicago, Chicago, Illinois, USA

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Immunotherapy biomarkers
Published: 16 July 2021 in Journal for ImmunoTherapy of Cancer
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Background Tumor-infiltrating CD8+ T cells and neoantigens are predictors of a favorable prognosis and response to immunotherapy with checkpoint inhibitors in many types of adult cancer, but little is known about their role in pediatric malignancies. Here, we analyzed the prognostic strength of T cell-inflamed gene expression and neoantigen load in high-risk neuroblastoma. We also compared transcriptional programs in T cell-inflamed and non-T cell-inflamed high-risk neuroblastomas to investigate possible mechanisms of immune exclusion. Methods A defined T cell-inflamed gene expression signature was used to categorize high-risk neuroblastomas in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n=123), and the Gabriella Miller Kids First (GMKF) program (n=48) into T cell-inflamed, non-T cell-inflamed, and intermediate groups. Associations between the T cell-inflamed and non-T cell-inflamed group, MYCN amplification, and survival were analyzed by Cox proportional hazards models. Additional survival analysis was conducted after integrating neoantigen load predicted from somatic mutations. Pathways activated in non-T cell-inflamed relative to T cell-inflamed tumors were analyzed using causal network analysis. Results Patients with T cell-inflamed high-risk tumors showed improved overall survival compared with those with non-T cell-inflamed tumors (p<0.05), independent of MYCN amplification status, in both TARGET and GMKF cohorts. Higher neoantigen load was also associated with better event-free and overall survival (p<0.005) and was independent of the T cell-inflamed signature. Activation of MYCN, ASCL1, SOX11, and KMT2A transcriptional programs was inversely correlated with the T cell-inflamed signature in both cohorts. Conclusions Our results indicate that tumors from children with high-risk neuroblastoma harboring a strong T cell-inflamed signature have a more favorable clinical outcome, and neoantigen load is a prognosis predictor, independent of T cell inflammation. Strategies to target SOX11 and other signaling pathways associated with non-T cell-inflamed tumors should be pursued as potential immune-potentiating interventions.

ACS Style

Riyue Bao; Stefani Spranger; Kyle Hernandez; Yuanyuan Zha; Peter Pytel; Jason J Luke; Thomas F Gajewski; Samuel L Volchenboum; Susan L Cohn; Ami V Desai. Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma. Journal for ImmunoTherapy of Cancer 2021, 9, e002417 .

AMA Style

Riyue Bao, Stefani Spranger, Kyle Hernandez, Yuanyuan Zha, Peter Pytel, Jason J Luke, Thomas F Gajewski, Samuel L Volchenboum, Susan L Cohn, Ami V Desai. Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma. Journal for ImmunoTherapy of Cancer. 2021; 9 (7):e002417.

Chicago/Turabian Style

Riyue Bao; Stefani Spranger; Kyle Hernandez; Yuanyuan Zha; Peter Pytel; Jason J Luke; Thomas F Gajewski; Samuel L Volchenboum; Susan L Cohn; Ami V Desai. 2021. "Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma." Journal for ImmunoTherapy of Cancer 9, no. 7: e002417.

Research article
Published: 10 October 2019 in Pediatric Blood & Cancer
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Background GD2 is a ganglioside that is ubiquitously expressed in the plasma membrane of neuroblastoma and is shed into the circulation. Procedure GD2 was measured with a high‐pressure liquid chromatography/tandem mass spectrometry assay in serum or plasma from 40 children without cancer (controls) and in biobanked samples from 128 (73 high‐risk) children with neuroblastic tumors at diagnosis, 56 children with relapsed neuroblastoma, 14 children with high‐risk neuroblastoma after treatment, and 8 to 12 children each with 10 other common childhood cancers at diagnosis. Results The C18 (18 carbon fatty acid) lipoform was the predominant circulating form of GD2 in controls and in patients with neuroblastoma. The median concentration of GD2 in children with high‐risk neuroblastoma at diagnosis was 167 nM (range, 16.1‐1060 nM), which was 30‐fold higher than the median concentration (5.6 nM) in controls. GD2 was not elevated in serum from children with the differentiated neuroblastic tumors, ganglioneuroma (n = 10) and ganglioneuroblastoma‐intermixed subtype (n = 12), and in children with 10 other childhood cancers. GD2 concentrations were significantly higher in serum from children with MYCN‐amplified tumors (P = 0.0088), high‐risk tumors (P < 0.00001), International Neuroblastoma Staging System (INSS) stage 4 tumors (P < 0.00001), and in children who died (P = 0.034). Conclusions Circulating GD2 appears to be a specific and sensitive tumor biomarker for high‐risk/high‐stage neuroblastoma and may prove to be clinically useful as a diagnostic or prognostic circulating tumor biomarker. GD2 will be measured prospectively and longitudinally in children enrolled on a high‐risk neuroblastoma treatment trial to assess its ability to measure response to treatment and predict survival.

ACS Style

Frank Milton Balis; Christine Maria Busch; Ami Vijay Desai; Emily Hibbitts; Arlene Naranjo; Rochelle Bagatell; Meredith Irwin; Elizabeth Fox. The ganglioside G D2 as a circulating tumor biomarker for neuroblastoma. Pediatric Blood & Cancer 2019, 67, e28031 -e28031.

AMA Style

Frank Milton Balis, Christine Maria Busch, Ami Vijay Desai, Emily Hibbitts, Arlene Naranjo, Rochelle Bagatell, Meredith Irwin, Elizabeth Fox. The ganglioside G D2 as a circulating tumor biomarker for neuroblastoma. Pediatric Blood & Cancer. 2019; 67 (1):e28031-e28031.

Chicago/Turabian Style

Frank Milton Balis; Christine Maria Busch; Ami Vijay Desai; Emily Hibbitts; Arlene Naranjo; Rochelle Bagatell; Meredith Irwin; Elizabeth Fox. 2019. "The ganglioside G D2 as a circulating tumor biomarker for neuroblastoma." Pediatric Blood & Cancer 67, no. 1: e28031-e28031.

Review
Published: 11 February 2019 in Children
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Neuroblastoma is a tumor with great clinical heterogeneity. Patients in North America are risk-stratified using a number of features including age at diagnosis, disease stage, tumor histology, MYCN status (amplified versus nonamplified), and tumor cell ploidy. In this paper, we review the evidence for utilizing these features in the risk classification of neuroblastic tumors. Additionally, we review the clinical and biologic criteria used by various cooperative groups to define low, intermediate, and high-risk disease populations in clinical trials, highlighting the differences in risk classification internationally. Finally, we discuss the development of the International Neuroblastoma Risk Group classification system, designed to begin worldwide standardization of neuroblastoma pretreatment risk classification and allow comparison of clinical trials conducted through different cooperative groups.

ACS Style

Elizabeth Sokol; Ami Desai. The Evolution of Risk Classification for Neuroblastoma. Children 2019, 6, 27 .

AMA Style

Elizabeth Sokol, Ami Desai. The Evolution of Risk Classification for Neuroblastoma. Children. 2019; 6 (2):27.

Chicago/Turabian Style

Elizabeth Sokol; Ami Desai. 2019. "The Evolution of Risk Classification for Neuroblastoma." Children 6, no. 2: 27.

Clinical trial
Published: 11 September 2018 in Pediatric Blood & Cancer
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1 Background At diagnosis, there are prognostic implications of low‐level leukemic blasts (CNS 2) in the cerebrospinal fluid (CSF) of patients with acute lymphoblastic leukemia (ALL). However, the significance of post‐induction CNS 2 results and the impact of equipment on CNS 2 prevalence have not been well studied. 2 Procedure A single‐institution retrospective cohort study was conducted to analyze the outcome of patients with ≥1 post‐induction CNS 2. A subanalysis compared the proportion of CNS 2 CSF results using 2 different cytocentrifuges; the Shandon Cytospin used from 2005 to 2008 and the Wescor Cytopro used from 2010 to 2014. 3 Results Over 4500 post‐induction CSF samples were analyzed, of which 59 were CNS 2. In covariate‐adjusted analyses, post‐induction CNS 2 did not significantly increase relapse risk. The proportion of CNS 2 results increased 4.3‐fold in noninfants and 6.3‐fold in infants using the Wescor Cytopro. Cytocentrifuge machine did not affect CNS 3 prevalence. 4 Conclusions These findings support our current practice of not changing management based on a post‐induction CNS 2 CSF and highlight how equipment changes can significantly influence testing results. More data are needed to analyze relapse by subpopulations, such as those with repeated CNS 2 findings.

ACS Style

Arun Gurunathan; Ami V. Desai; L. Charles Bailey; Yimei Li; John K. Choi; Susan R. Rheingold. Significance of CNS 2 cerebrospinal fluid status post-induction in pediatric and adolescent patients with acute lymphoblastic leukemia. Pediatric Blood & Cancer 2018, 66, e27433 .

AMA Style

Arun Gurunathan, Ami V. Desai, L. Charles Bailey, Yimei Li, John K. Choi, Susan R. Rheingold. Significance of CNS 2 cerebrospinal fluid status post-induction in pediatric and adolescent patients with acute lymphoblastic leukemia. Pediatric Blood & Cancer. 2018; 66 (1):e27433.

Chicago/Turabian Style

Arun Gurunathan; Ami V. Desai; L. Charles Bailey; Yimei Li; John K. Choi; Susan R. Rheingold. 2018. "Significance of CNS 2 cerebrospinal fluid status post-induction in pediatric and adolescent patients with acute lymphoblastic leukemia." Pediatric Blood & Cancer 66, no. 1: e27433.

Comparative study
Published: 01 August 2018 in Pediatric Blood & Cancer
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1 Background High‐dose chemotherapy with autologous stem cell rescue (HDC‐ASCR) has improved event‐free survival for children with high‐risk neuroblastoma. Common regimens include carboplatin/etoposide/melphalan (CEM), busulfan/melphalan (BuMel), and tandem HDC‐ASCR [thiotepa/cyclophosphamide (TC) followed by CEM]. To complement clinical trial data and to evaluate the clinical burden associated with these regimens, resource ultilization (RU) was evaluated. An administrative database was used to evaluate RU in a previously developed high‐risk neuroblastoma cohort. Single CEM and BuMel patients were followed for 60 days from the first day of the HDC‐ASCR preparative regimen or until death, whichever came first. Tandem patients were followed from the first day of the first HDC‐ASCR preparative regimen through day 60 from the first day of the second HDC‐ASCR. Resources compared included inpatient days, ICU‐level care, and medications administered. 2 Results A cohort of 578 patients was evaluated; 422 patients underwent single HDC‐ASCR with CEM, 67 received BuMel, 72 underwent TC/CEM, and 17 received only the first portion of tandem HDC‐ASCR. The median number of inpatient days and days of exposure to antibiotics, opioids, and total parenteral nutrition were higher in the tandem group than in the CEM and BuMel groups. However, the rate of use of several ICU‐level resources per 1000 hospital days was lower for the tandem group. 3 Conclusions These data suggest that while patients undergoing tandem HDC‐ASCR were hospitalized longer, the severity of illness during hospitalization was not greater in tandem patients.

ACS Style

Ami V. Desai; Yimei Li; Kelly Getz; Alix E. Seif; Brian Fisher; Vera Huang; Richard Aplenc; Rochelle Bagatell. Resource utilization and toxicities after single versus tandem autologous stem cell rescue in high-risk neuroblastoma using a national administrative database. Pediatric Blood & Cancer 2018, 65, e27372 .

AMA Style

Ami V. Desai, Yimei Li, Kelly Getz, Alix E. Seif, Brian Fisher, Vera Huang, Richard Aplenc, Rochelle Bagatell. Resource utilization and toxicities after single versus tandem autologous stem cell rescue in high-risk neuroblastoma using a national administrative database. Pediatric Blood & Cancer. 2018; 65 (12):e27372.

Chicago/Turabian Style

Ami V. Desai; Yimei Li; Kelly Getz; Alix E. Seif; Brian Fisher; Vera Huang; Richard Aplenc; Rochelle Bagatell. 2018. "Resource utilization and toxicities after single versus tandem autologous stem cell rescue in high-risk neuroblastoma using a national administrative database." Pediatric Blood & Cancer 65, no. 12: e27372.

Case reports
Published: 01 July 2017 in Journal of Pediatric Hematology/Oncology
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Behcet disease is a potentially life-threatening multisystemic vasculitis with thrombotic tendency. Mucocutaneous ulcers, arthritis, and uveitis are the most recognizable features, but may be absent at the time of medical evaluation. We report a case in which a 8-year old patient presented with spontaneous bilateral lower extremity deep venous thromboses, and screening for rheumatologic symptoms led to diagnosing Behcet. This case demonstrates that deep venous thromboses can be the initial event bringing a patient with Behcet to medical attention, highlighting the importance of screening for underlying rheumatologic diseases in pediatric patients who present with unprovoked thrombosis.

ACS Style

Arun Gurunathan; David Teachey; Kudakwashe R. Chikwava; Char Witmer; Ami V. Desai. Behcet Disease Initially Presenting as Deep Venous Thrombosis: A Case Report. Journal of Pediatric Hematology/Oncology 2017, 39, 410 -412.

AMA Style

Arun Gurunathan, David Teachey, Kudakwashe R. Chikwava, Char Witmer, Ami V. Desai. Behcet Disease Initially Presenting as Deep Venous Thrombosis: A Case Report. Journal of Pediatric Hematology/Oncology. 2017; 39 (5):410-412.

Chicago/Turabian Style

Arun Gurunathan; David Teachey; Kudakwashe R. Chikwava; Char Witmer; Ami V. Desai. 2017. "Behcet Disease Initially Presenting as Deep Venous Thrombosis: A Case Report." Journal of Pediatric Hematology/Oncology 39, no. 5: 410-412.