- Pediatric Neuro-Immuno-Oncology
- Pediatric Neuro-Oncology
- Neurology with Special Qualifications in Child Neurology
Clinical Instructor, Neurology & Neurological Sciences
Honors & Awards
The Leonard Tow Humanism in Medicine Award, Arnold P. Gold Foundation (2015)
Cal Turner Program for Moral Leadership in Professions Fellow, Cal Turner Program (2014)
Phi Beta Kappa, Phi Beta Kappa (2010)
SMU President's Scholar, Southern Methodist University (2007-2011)
Boards, Advisory Committees, Professional Organizations
Member, Children's Oncology Group (2021 - Present)
Member, Society of Neuro-Oncology (2020 - Present)
Member, Child Neurology Society (2017 - Present)
Member, American Academy of Neurology (2017 - Present)
Member, Gold Humanism Honor Society (2015 - Present)
Member, Phi Beta Kappa (2010 - Present)
Board Certification: American Board of Psychiatry and Neurology, Neurology with Special Qualifications in Child Neurology (2020)
Fellowship: Stanford Hospital and Clinics Neuro-Immunology-Oncology (2022) CA
Fellowship: Stanford Hospital and Clinics Neuro-Oncology Fellowship (2021) CA
Residency: Washington University in St. Louis GME Verifications (2020) MO
Internship: Washington University in St. Louis GME Verifications (2017) MO
Medical Education: Vanderbilt University School of Medicine (2015) TN
Pediatric Neuro-Oncology Fellow, Lucile Packard Children's Hospital at Stanford University
MD, Vanderbilt University School of Medicine, Doctor of Medicine (2015)
BS and BA, Southern Methodist University, Biochemistry and History (2011)
B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Recurrent Glioblastoma Multiforme
This is an open label, non-randomized, single site Phase I study to test the manufacturing feasibility and safety of locoregional (LR) administration of B7-H3CART into the central nervous system of adult subjects with recurrent IDH wild-type GBM using a standard 3+3 dose escalation design.
GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG)
The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults with H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) or spinal H3K27M-mutant diffuse midline glioma (DMG). H3K27Mmutant testing will occur as part of standard of care prior to enrollment.
- TUMOR INFLAMMATION-ASSOCIATED NEUROTOXICITY (TIAN): A TOXICITY SYNDROME IN PATIENTS TREATED WITH IMMUNOTHERAPY FOR CENTRAL NERVOUS SYSTEM TUMORS OXFORD UNIV PRESS INC. 2023
Tumor inflammation-associated neurotoxicity.
Cancer immunotherapies have unique toxicities. Establishment of grading scales and standardized grade-based treatment algorithms for toxicity syndromes can improve the safety of these treatments, as observed for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) in patients with B cell malignancies treated with chimeric antigen receptor (CAR) T cell therapy. We have observed a toxicity syndrome, distinct from CRS and ICANS, in patients treated with cell therapies for tumors in the central nervous system (CNS), which we term tumor inflammation-associated neurotoxicity (TIAN). Encompassing the concept of 'pseudoprogression,' but broader than inflammation-induced edema alone, TIAN is relevant not only to cellular therapies, but also to other immunotherapies for CNS tumors. To facilitate the safe administration of cell therapies for patients with CNS tumors, we define TIAN, propose a toxicity grading scale for TIAN syndrome and discuss the potential management of this entity, with the goal of standardizing both reporting and management.
View details for DOI 10.1038/s41591-023-02276-w
View details for PubMedID 37024595
View details for PubMedCentralID 7238960
- Stroke Mimics Are Not Benign in Immunocompromised Children. Stroke 2022: 101161STROKEAHA122039311
Major tumor regressions in H3K27M-mutated diffuse midline glioma (DMG) following sequential intravenous (IV) and intracerebroventricular (ICV) delivery of GD2-CAR T cells
AMER ASSOC CANCER RESEARCH. 2022
View details for Web of Science ID 000892509500153
MAJOR TUMOR REGRESSIONS IN H3K27M-MUTATED DIFFUSE MIDLINE GLIOMA (DMG) FOLLOWING SEQUENTIAL INTRAVENOUS (IV) AND INTRACEREBROVENTRICULAR (ICV) DELIVERY OF GD2-CAR T-CELLS
OXFORD UNIV PRESS INC. 2022: 20-21
View details for Web of Science ID 000840122400074
GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas.
Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMG) are universally lethal paediatric central nervous system tumours1. We previously discovered that the disialoganglioside GD2 is highly expressed on H3K27M-mutant glioma cells and demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells2, providing the rationale for a first-in-human Phase 1 clinical trial (NCT04196413). Because CAR T-cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure, and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutant DIPG/DMG treated with GD2-CAR T cells (GD2-CART) at dose level 1 (1e6 GD2-CAR T cells/kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T infusions administered intracerebroventricularly3. Toxicity was largely related to tumor location and reversible with intensive supportive care. On-target, off-tumor toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Proinflammatory cytokines were increased in plasma and cerebrospinal fluid (CSF). Transcriptomic analyses of 65,598 single cells from CAR T cell products and CSF elucidate heterogeneity in response between subjects and administration routes. These early results underscore the promise of this approach for H3K27M+ DIPG/DMG therapy.
View details for DOI 10.1038/s41586-022-04489-4
View details for PubMedID 35130560
GD2 CAR T cells mediate clinical activity and manageable toxicity in children and young adults with DIPG and H3K27M-mutated diffuse midline gliomas.
AMER ASSOC CANCER RESEARCH. 2021
View details for Web of Science ID 000680263501014
- SINGLE CELL RNA SEQUENCING FROM THE CSF OF SUBJECTS WITH H3K27M+DIPG/DMG TREATED WITH GD2 CAR T-CELLULAR THERAPY OXFORD UNIV PRESS INC. 2021: 39
- "STROKE MIMICS" ARE NOT BENIGN IN IMMUNOCOMPROMISED CHILDREN OXFORD UNIV PRESS INC. 2021: 28
- GD2 CAR T-CELLS MEDIATE CLINICAL ACTIVITY AND MANAGEABLE TOXICITY IN CHILDREN AND YOUNG ADULTS WITH H3K27M-MUTATED DIPG AND SPINAL CORD DMG OXFORD UNIV PRESS INC. 2021: 49-50
Nonoptic pathway tumors in children with neurofibromatosis type 1.
2020; 95 (8): e1052-e1059
To define the radiologic features and natural history of nonoptic pathway tumors (non-OPTs) in children with neurofibromatosis type 1 (NF1).We performed a retrospective cross-sectional analysis of 64 children with NF1 harboring 100 probable non-OPTs. Age at diagnosis, sex, tumor location, number of tumors, symptomology, concurrent OPT, radiographic progression (defined as qualitative and quantitative increases in size), and treatment were assessed. Tumor volumes were measured from initial presentation until treatment or end of disease progression.Sixty-three percent of probable non-OPTs progressed over time, where radiographic progression was concomitantly associated with clinical progression. Fifty-two percent of patients had incidentally identified probable non-OPTs. Twenty-five percent of patients were symptomatic at initial diagnosis, all of whom harbored tumors that grew on subsequent scans and required tumor-directed therapy. There were no clinical differences between probable non-OPTs localized to the brainstem vs other locations with respect to age, sex, concurrent optic pathway glioma, symptomology, and treatment. The average time from diagnosis to stabilization or decrease in tumor size was 2.34 years (SD, 2.15 years). Nineteen biopsied lesions were all histopathologically confirmed as tumor. Six children (9%) had deep extensive tumors, who presented earlier (mean age at diagnosis, 3.88 years), required multiple treatments, and had a shorter mean progression-free survival (48 months).Over half of children with NF1 in this study developed probable non-OPTs, the majority of which were clinically and radiographically progressive. While brainstem and nonbrainstem gliomas share similar clinical features and natural history, deep extensive tumors comprise a distinct aggressive group of tumors that warrant close attention.
View details for DOI 10.1212/WNL.0000000000009458
View details for PubMedID 32300062
View details for PubMedCentralID PMC7668552
Increased prevalence of brain tumors classified as T2 hyperintensities in neurofibromatosis 1.
Neurology. Clinical practice
2018; 8 (4): 283-291
We sought to define the radiologic features that differentiate neoplastic from non-neoplastic T2 hyperintensities (T2Hs) in neurofibromatosis type 1 (NF1) and identify those lesions most likely to require oncologic surveillance.We conducted a single-center retrospective review of all available brain MRIs from 68 children with NF1 (n = 190) and 46 healthy pediatric controls (n = 104). All T2Hs identified on MRI were characterized based on location, border, shape, degree of T1 hypointensity, and presence of mass effect or contrast enhancement, and subsequently classified using newly established radiologic criteria as either unidentified bright objects (UBOs) or probable tumors. Lesion classification was pathologically confirmed in 10 NF1 cases.T2Hs were a highly sensitive (94.4%; 95% confidence interval [CI] 86.4%-98.5%) and specific (100.0%; 95% CI 92.3%-100.0%) marker for the diagnosis of NF1. UBOs constituted the majority of T2Hs (82%) and were most frequently located in cerebellar white matter, medial temporal lobe, and thalamus, where they were more likely than probable tumors to be bilateral (p < 0.001) and have nondiscrete borders (p < 0.001). Surprisingly, 57% of children with T2Hs harbored lesions classified as probable tumors, and 28% of children with probable tumors received treatment. In contrast to UBOs, probable tumors were most frequently located within the globus pallidus and medulla, and rarely occurred prior to 3 years of age.With the implementation of standardized radiologic criteria, a high prevalence of brain tumors was identified in this at-risk population of children, of which nearly one-third required treatment, emphasizing the need for appropriate oncologic surveillance for patients with NF1 harboring nonoptic pathway brain tumors.
View details for DOI 10.1212/CPJ.0000000000000494
View details for PubMedID 30140579
View details for PubMedCentralID PMC6105062
A multi-institutional study of brainstem gliomas in children with neurofibromatosis type 1.
2017; 88 (16): 1584-1589
To define the clinical and radiologic features of brainstem gliomas (BSGs) in children with neurofibromatosis type 1 (NF1).We performed a retrospective cross-sectional study of 133 children with NF1 and concurrent BSGs cared for at 4 NF1 referral centers. BSG was determined using radiographic criteria. Age at diagnosis, tumor location and appearance, clinical symptoms, treatment, and presence of a concurrent optic pathway glioma were assessed.The average age at BSG diagnosis was 7.2 years, and tumors occurred most often in the midbrain and medulla (66%). The majority of children with NF1-BSGs were asymptomatic (54%) and were not treated (88%). Only 9 of the 72 asymptomatic children received treatment because of progressive tumor enlargement. In contrast, 61 children presented with clinical signs/symptoms attributable to their BSG; these individuals were older and more often had focal lesions. Thirty-one patients underwent treatment for their tumor, and 14 received CSF diversion only. Progression-free survival was ∼3 years shorter for children receiving tumor-directed therapy relative to those who had either no treatment or CSF diversion only. Overall survival was 85% for the tumor-directed therapy group, whereas no deaths were reported in the untreated or CSF diversion groups.Unlike children with sporadically occurring BSGs, most children with NF1-BSGs were asymptomatic, and few individuals died from complications of their tumor. Those requiring tumor-directed treatment tended to be older children with focal lesions, and had clinically more aggressive disease relative to those who were not treated or underwent CSF diversion only.
View details for DOI 10.1212/WNL.0000000000003881
View details for PubMedID 28330960
View details for PubMedCentralID PMC5395076
Pediatric Acute Stroke Protocol Activation in a Children's Hospital Emergency Department.
2015; 46 (8): 2328-31
Pediatric acute stroke teams are a new phenomenon. We sought to characterize the final diagnoses of children with brain attacks in the emergency department where the pediatric acute stroke protocol was activated and to describe the time to neurological evaluation and neuroimaging.Clinical and demographic information was obtained from a quality improvement database and medical records for consecutive patients (age, ≤20 years) presenting to a single institution's pediatric emergency department where the acute stroke protocol was activated between April 2011 and October 2014. Stroke protocol activation means that a neurology resident evaluates the child within 15 minutes, and urgent magnetic resonance imaging is available.There were 124 stroke alerts (age, 11.2±5.2 years; 63 boys/61 girls); 30 were confirmed strokes and 2 children had a transient ischemic attack. Forty-six of 124 (37%) cases were healthy children without any significant medical history. Nonstroke neurological emergencies were found in 17 children (14%); the majority were meningitis/encephalitis (n=5) or intracranial neoplasm (n=4). Other common final diagnoses were complex migraine (17%) and seizure (15%). All children except 1 had urgent neuroimaging. Magnetic resonance imaging was the first study in 76%. The median time from emergency department arrival to magnetic resonance imaging was 94 minutes (interquartile range, 49-151 minutes); the median time to computed tomography was 59 minutes (interquartile range, 40-112 minutes).Of pediatric brain attacks, 24% were stroke, 2% were transient ischemic attack, and 14% were other neurological emergencies. Together, 40% had a stroke or other neurological emergency, underscoring the need for prompt evaluation and management of children with brain attacks.
View details for DOI 10.1161/STROKEAHA.115.009961
View details for PubMedID 26138119
A multispecialty pediatric neurovascular conference: a model for interdisciplinary management of complex disease.
2015; 52 (2): 165-73
In 2013, our institution established a multidisciplinary pediatric neurovascular conference for coordination of care. Here, we review our initial experience.Clinical and demographic data were obtained from medical records for patients presented to the pediatric neurovascular conference from April 2013 to July 2014. Patient descriptive characteristics were described by mean and standard deviation for continuous measures and by number and percent for categorical measures. Patients were secondarily stratified by lesion/disease type, and descriptive statistics were used to measure demographic and clinical variables.The pediatric neurovascular conference met 26 times in the study period. Overall, 75 children were presented to the conference over a 15-month period. The mean age was 9.8 (standard deviation, 6.3) years. There were 42 (56%) male patients. These 75 children were presented a total of 112 times. There were 28 (37%) patients with history of stroke. Complex vascular lesions were the most frequently discussed entity; of 62 children (83%) with a diagnosed vascular lesion, brain arteriovenous malformation (29%), cavernous malformation (15%), and moyamoya (11%) were most common. Most discussions were for review of imaging (35%), treatment plan formulation (27%), the need for additional imaging (25%), or diagnosis (13%). Standardized care protocols for arteriovenous malformation and moyamoya were developed.A multidisciplinary conference among a diverse group of providers guides complex care decisions, helps standardize care protocols, promotes provider collaboration, and supports continuity of care in pediatric neurovascular disease.
View details for DOI 10.1016/j.pediatrneurol.2014.10.010
View details for PubMedID 25693581