- Pediatric Hematology-Oncology
Clinical Associate Professor, Pediatrics - Hematology & Oncology
Board Certification: American Board of Pediatrics, Pediatric Hematology-Oncology (2019)
Fellowship: NY Presbyterian Hospital Columbia Pediatric Hematology and Oncology Fellowship (2017) NY
Board Certification: American Board of Pediatrics, Pediatrics (2014)
Residency: Children's Hospital of Philadelphia Pediatric Residency (2014) PA
Medical Education: Indiana University School of Medicine (2011) IN
Pediatric Hem/Onc Fellowship, New York Presbyterian Hospital-Columbia University School of Medicine (2017)
Pediatric Residency, Children's Hospital of Philadelphia (2014)
MD, Indiana University School of Medicine (2011)
BA, Columbia University (2006)
A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated Diseases
The purpose of this study is to assess the efficacy and safety of tabelecleucel in participants with Epstein-Barr virus (EBV) associated diseases.
Trastuzumab Deruxtecan for the Treatment of HER2+ Newly Diagnosed or Recurrent Osteosarcoma
This phase II trial studies the effects of trastuzumab deruxtecan in treating patients with HER2 positive osteosarcoma that is newly diagnosed or has come back (recurrent). Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them.
Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.
Brentuximab Vedotin Following Autologous Transplantation in Pediatric Patients with Relapsed/Refractory Hodgkin Lymphoma.
Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with approximately 50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplant (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy following ASCT for the treatment of relapsed/refractory HL to describe the experience of this regimen in the pediatric population. This is the largest cohort reported to date. We found that brentuximab vedotin was well tolerated with a safety profile similar to adult patients. With a median follow up of 37 months, the 3-year PFS was 85%. These data suggest a potential role for the use of brentuximab vedotin as consolidation therapy after ASCT for children with relapsed/refractory Hodgkin lymphoma.
View details for DOI 10.1182/bloodadvances.2022009323
View details for PubMedID 36897253
Cellular and humoral immunotherapy in children, adolescents and young adults with non-Hodgkin lymphoma.
Best practice & research. Clinical haematology
2023; 36 (1): 101442
The prognosis is dismal (2-year overall survival less than 25%) for childhood, adolescent, and young adult (CAYA) with relapsed and/or refractory (R/R) non-Hodgkin lymphoma (NHL). Novel targeted therapies are desperately needed for this poor-risk population. CD19, CD20, CD22, CD79a, CD38, CD30, LMP1 and LMP2 are attractive targets for immunotherapy in CAYA patients with R/R NHL. Novel anti-CD20 monoclonal antibodies, anti-CD38 monoclonal antibody, antibody drug conjugates and T and natural killer (NK)-cell bispecific and trispecific engagers are being investigated in the R/R setting and are changing the landscape of NHL therapy. A variety of cellular immunotherapies such as viral activated cytotoxic T-lymphocyte, chimeric antigen receptor (CAR) T-cells, NK and CAR NK-cells have been investigated and provide alternative options for CAYA patients with R/R NHL. Here, we provide an update and clinical practice guidance of utilizing these cellular and humoral immunotherapies in CAYA patients with R/R NHL.
View details for DOI 10.1016/j.beha.2023.101442
View details for PubMedID 36907635
Multicenter study of pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders.
BACKGROUND: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorder [EBV(-)M-PTLD] comprises approximately 10% of M-PTLD. No large multi-institutional pediatric-specific reports on treatment and outcome are available.METHODS: A multi-institutional retrospective review of solid organ recipients diagnosed with EBV(-)M-PTLD aged ≤21years between 2001 and 2020 in 12 centers in the United States and United Kingdom was performed, including demographics, staging, treatment, and outcomes data.RESULTS: Thirty-six patients were identified with EBV(-)M-PTLD. Twenty-three (63.9%) were male. Median age (range) at transplantation, diagnosis of EBV(-)M-PTLD, and interval from transplant to PTLD were 2.2 years (0.1-17), 14 years (3.0-20), and 8.5 years (0.6-18.3), respectively. Kidney (n=17 [47.2%]) and heart (n=13 [36.1%]) were the most commonly transplanted organs. Most were Murphy stage III (n=25 [69.4%]). Lactate dehydrogenase was elevated in 22/34 (64.7%) and ≥2 times upper limit of normal in 11/34 (32.4%). Pathological diagnoses included diffuse large B-cell lymphoma (n=31 [86.1%]) and B-non-Hodgkin lymphoma (B-NHL) not otherwise specified (NOS) (n=5 [13.9%]). Of nine different regimens used, the most common were: pediatric mature B-NHL-specific regimen (n=13 [36.1%]) and low-dose cyclophosphamide, prednisone, and rituximab (n=9 [25%]). Median follow-up from diagnosis was 3.0 years (0.3-11.0 years). Three-year event-free survival (EFS) and overall survival (OS) were 64.8% and 79.9%, respectively. Of the seven deaths, six were from progressive disease.CONCLUSIONS: EFS and OS were comparable to pediatric EBV(+) PTLD, but inferior to mature B-NHL in immunocompetent pediatric patients. The wide range of therapeutic regimens used directs our work toward developing an active multi-institutional registry to design prospective studies.PLAIN LANGUAGE SUMMARY: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders (EBV(-)M-PTLD) have comparable outcomes to EBV(+) PTLD, but are inferior to diffuse large B-cell lymphoma in immunocompetent pediatric patients. The variety of treatment regimens used highlights the need to develop a pediatric PTLD registry to prospectively evaluate outcomes. The impact of treatment regimen on relapse risk could not be assessed because of small numbers. In the intensive pediatric B-non-Hodgkin lymphoma chemoimmunotherapy group, 11 of 13 patients remain alive in complete remission after 0.6 to 11years.
View details for DOI 10.1002/cncr.34600
View details for PubMedID 36571557
Burkitt lymphoma after solid-organ transplant: Treatment and outcomes in the paediatric PTLD collaborative.
British journal of haematology
Burkitt lymphoma arising in paediatric post-solid-organ transplantation-Burkitt lymphoma (PSOT-BL) is a clinically aggressive malignancy and a rare form of post-transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT-BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1-14) and age at PSOT-BL diagnosis was 8.0 years (range: 1-17). All but one patient had late onset of PSOT-BL (≥2 years post-transplant), with a median interval from transplant to PSOT-BL diagnosis of 4.0 years (range: 0.4-12). Heart (n = 18 [51.4%]) and liver (n = 13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment-related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma-specific French-American-British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low-intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow-up was 6.7 years (range: 0.5-17). Three-year event-free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT-BL patients receiving BL-specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi-institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT-BL.
View details for DOI 10.1111/bjh.18498
View details for PubMedID 36454546
Development of clinical pathways to improve multidisciplinary care of high-risk pediatric oncology patients.
Frontiers in oncology
2022; 12: 1033993
Clinical pathways are evidence-based tools that have been integrated into many aspects of pediatric hospital medicine and have proven effective at reducing in-hospital complications from a variety of diseases. Adaptation of similar tools for specific, high-risk patient populations in pediatric oncology has been slower, in part due to patient complexities and variations in management strategies. There are few published studies of clinical pathways for pediatric oncology patients. Pediatric patients with a new diagnosis of leukemia or lymphoma often present with one or more "oncologic emergencies" that require urgent intervention and deliberate multidisciplinary care to prevent significant consequences. Here, we present two clinical pathways that have recently been developed using a multidisciplinary approach at a single institution, intended for the care of patients who present with hyperleukocytosis or an anterior mediastinal mass. These clinical care pathways have provided a critical framework for the immediate care of these patients who are often admitted to the pediatric intensive care unit for initial management. The goal of the pathways is to facilitate multidisciplinary collaborations, expedite diagnosis, and streamline timely treatment initiation. Standardizing the care of high-risk pediatric oncology patients will ultimately decrease morbidity and mortality associated with these diseases to increase the potential for excellent outcomes.
View details for DOI 10.3389/fonc.2022.1033993
View details for PubMedID 36523979
View details for PubMedCentralID PMC9744920
Viral cfDNA Profiling Reveals Distinct EBV Subtypes and Stratifies Risk in Hodgkin Lymphomas
AMER SOC HEMATOLOGY. 2022: 1318-1319
View details for DOI 10.1182/blood-2022-159230
View details for Web of Science ID 000893223201135
End of Treatment Positron Emission Tomography Response and Outcomes in Post-Transplant Lymphoproliferative Disorder
AMER SOC HEMATOLOGY. 2022: 9559-9560
View details for DOI 10.1182/blood-2022-165443
View details for Web of Science ID 000893230302246
Distinct Molecular Subtypes of Classic Hodgkin Lymphoma Identified By Comprehensive Noninvasive Profiling
AMER SOC HEMATOLOGY. 2022: 1295-1296
View details for DOI 10.1182/blood-2022-164744
View details for Web of Science ID 000893223201127
TREATMENT OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD): A MULTI-CENTER PEDIATRIC SERIES
View details for Web of Science ID 000859203900049
Validation of a non-oncogene encoded vulnerability to exportin 1 inhibition in pediatric renal tumors.
Med (New York, N.Y.)
Malignant rhabdoid tumors (MRTs) and Wilms' tumors (WTs) are rare and aggressive renal tumors of infants and young children comprising ∼5% of all pediatric cancers. MRTs are among the most genomically stable cancers, and although WTs are genomically heterogeneous, both generally lack therapeutically targetable genetic mutations.Comparative protein activity analysis of MRTs (n = 68) and WTs (n = 132) across TCGA and TARGET cohorts, using metaVIPER, revealed elevated exportin 1 (XPO1) inferred activity. In vitro studies were performed on a panel of MRT and WT cell lines to evaluate effects on proliferation and cell-cycle progression following treatment with the selective XPO1 inhibitor selinexor. In vivo anti-tumor activity was assessed in patient-derived xenograft (PDX) models of MRTs and WTs.metaVIPER analysis identified markedly aberrant activation of XPO1 in MRTs and WTs compared with other tumor types. All MRT and most WT cell lines demonstrated baseline, aberrant XPO1 activity with in vitro sensitivity to selinexor via cell-cycle arrest and induction of apoptosis. In vivo, XPO1 inhibitors significantly abrogated tumor growth in PDX models, inducing effective disease control with sustained treatment. Corroborating human relevance, we present a case report of a child with multiply relapsed WTs with prolonged disease control on selinexor.We report on a novel systems-biology-based comparative framework to identify non-genetically encoded vulnerabilities in genomically quiescent pediatric cancers. These results have provided preclinical rationale for investigation of XPO1 inhibitors in an upcoming investigator-initiated clinical trial of selinexor in children with MRTs and WTs and offer opportunities for exploration of inferred XPO1 activity as a potential predictive biomarker for response.This work was funded by CureSearch for Children's Cancer, Alan B. Slifka Foundation, NIH (U01 CA217858, S10 OD012351, and S10 OD021764), Michael's Miracle Cure, Hyundai Hope on Wheels, Cannonball Kids Cancer, Conquer Cancer the ASCO Foundation, Cycle for Survival, Paulie Strong Foundation, and the Grayson Fund.
View details for DOI 10.1016/j.medj.2022.09.002
View details for PubMedID 36195086
Targeting of the nuclear export protein XPO1 represents a non-genetically encoded vulnerability in malignant rhabdoid and Wilms tumors
AMER ASSOC CANCER RESEARCH. 2022
View details for Web of Science ID 000892509505490
Pediatric EBV-negative monomorphic post-solid organ transplant lymphoproliferative disorders [EBV(-)M-PTLD]: Characteristics, treatment, and outcome from 11 pediatric academic centers.
LIPPINCOTT WILLIAMS & WILKINS. 2022
View details for Web of Science ID 000863680300015
Early presentation of post-transplant lymphoproliferative disorders (PTLD) or tumor positivity for epstein-barr virus does not confer better patient survival: A multicenter pediatric series
View details for Web of Science ID 000783167500151
Practice patterns for the management of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL): an international survey by the Global NLPHL One Working Group (GLOW).
Leukemia & lymphoma
View details for DOI 10.1080/10428194.2022.2053533
View details for PubMedID 35357263
Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.
Journal of the National Comprehensive Cancer Network : JNCCN
2022; 20 (11): 1267-1275
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.
View details for DOI 10.6004/jnccn.2022.0057
View details for PubMedID 36351334
Outcome of Post Solid Organ Transplant Burkitt Lymphoma (PSOT-BL): A Report from the Pediatric PTLD Collaborative (PPC)
AMER SOC HEMATOLOGY. 2021
View details for DOI 10.1182/blood-2021-149033
View details for Web of Science ID 000736413902015
Brentuximab Vedotin As Consolidation Therapy Following Autologous Stem Cell Transplantation in Children and Adolescents with Relapsed/Refractory Hodgkin Lymphoma: A Multi-Center Retrospective Analysis
AMER SOC HEMATOLOGY. 2021
View details for DOI 10.1182/blood-2021-151808
View details for Web of Science ID 000736413901194
Improving Risk Stratification to Guide Treatment Decisions for Children, Adolescents, and Young Adults With Hodgkin Lymphoma
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2021; 19 (6): 666-668
View details for DOI 10.6004/jnccn.2021.7041
View details for Web of Science ID 000672859700004
View details for PubMedID 34214966
Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.
Journal of the National Comprehensive Cancer Network : JNCCN
2020; 18 (8): 1105–23
Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.
View details for DOI 10.6004/jnccn.2020.0036
View details for PubMedID 32755986
Expert consensus statements for Waldeyer's ring involvement in pediatric Hodgkin lymphoma: The staging, evaluation, and response criteria harmonization (SEARCH) for childhood, adolescent, and young adult Hodgkin lymphoma (CAYAHL) group.
Pediatric blood & cancer
Waldeyer's ring (WR) involvement in pediatric Hodgkin lymphoma (HL) is extremely rare and criteria for determining involvement and response to treatment are unclear. The international Staging, Evaluation, and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) Group performed a systematic review of the literature in search of involvement or response criteria, or evidence to support specific criteria. Only 166 cases of HL with WR involvement were reported in the literature, 7 of which were pediatric. To date no standardized diagnostic or response assessment criteria are available. Given the paucity of evidence, using a modified Delphi survey technique, expert consensus statements were developed by the SEARCH group to allow for a more consistent definition of disease and response evaluation related to this rare site of involvement among pediatric oncologists. The available evidence and expert consensus statements are summarized.
View details for DOI 10.1002/pbc.28361
View details for PubMedID 32672879
Brentuximab Vedotin as Consolidation Therapy After Autologous Stem Cell Transplantation in Children and Adolescents (<18y) With Early Relapse Hodgkin Lymphoma.
Journal of pediatric hematology/oncology
We describe 6 pediatric patients (12 to 18y) with relapsed or refractory Hodgkin lymphoma treated with consolidative Brentuximab vedotin (Bv) following reinduction chemotherapy and autologous stem cell transplantation. The progression-free survival after autologous stem cell transplantation was 12, 18, 22, 24, 30, and 30 months. Most patients tolerated Bv well although 2 patients developed grade 3 neuropathy that prevent them from completing the scheduled 16 doses of Bv. Consolidative Bv in children and adolescents, as currently recommended for adult patients with early relapsed or refractory Hodgkin lymphoma, is feasible but with some significant toxicities.
View details for DOI 10.1097/MPH.0000000000001703
View details for PubMedID 31876780
Outcomes in intermediate-risk pediatric lymphocyte-predominant Hodgkin lymphoma: A report from the Children's Oncology Group.
Pediatric blood & cancer
2018; 65 (12): e27375
Optimal management of patients with intermediate-risk lymphocyte-predominant Hodgkin lymphoma (LPHL) is unclear due to their small numbers in most clinical trials. Children's Oncology Group AHOD0031, a randomized phase III trial of pediatric patients with intermediate-risk Hodgkin lymphoma (HL), included patients with LPHL. We report the outcomes of these patients and present directions for future therapeutic strategies.Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) followed by response evaluation. Slow early responders were randomized to two additional ABVE-PC cycles ± two dexamethasone, etoposide, cisplatin, and cytarabine cycles and all received involved field radiotherapy (IFRT). Rapid early responders (RERs) received two additional ABVE-PC cycles. RERs with complete response (CR) were randomized to IFRT or no further therapy. RERs without CR received IFRT.Ninety-six (5.6%) of 1711 patients on AHOD0031 had LPHL. Patients with LPHL were more likely to achieve RER (93.6% vs. 81.0%; P = 0.002) and CR (74.2% vs. 49.3%; P = 0.000005) following chemotherapy compared with patients with classical HL. Five-year event-free survival (EFS) was superior in patients with LPHL (92.2%) versus classical HL (83.5%) (P = 0.04), without difference in overall survival (OS). Among RERs with CR following chemotherapy (n = 33), there was no difference in EFS or OS between those randomized to receive or not receive IFRT.Children and adolescents with intermediate-risk LPHL represent ideal candidates for response-adapted therapy based on their favorable outcomes. The majority of patients treated with the ABVE-PC backbone achieve RER with CR status and can be treated successfully without IFRT.
View details for DOI 10.1002/pbc.27375
View details for PubMedID 30277639
View details for PubMedCentralID PMC6192844
Pericardial effusion in Hodgkin lymphoma: a report from the Children's Oncology Group AHOD0031 protocol
2018; 132 (11): 1208–11
View details for DOI 10.1182/blood-2018-02-834465
View details for Web of Science ID 000444425900016
View details for PubMedID 30061157
View details for PubMedCentralID PMC6137557
Stroke Prevalence in Children With Sickle Cell Disease in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.
Global pediatric health
2018; 5: 2333794X18774970
Objectives. The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods. Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. Results. Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion. Systematic review enabled the estimation of the number of children with SCD stroke in sub-Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions.
View details for DOI 10.1177/2333794X18774970
View details for PubMedID 29785408
View details for PubMedCentralID PMC5954575
Precision Medicine in Children and Young Adults with Hematologic Malignancies and Blood Disorders: The Columbia University Experience
FRONTIERS IN PEDIATRICS
2017; 5: 265
The advent of comprehensive genomic profiling has markedly advanced the understanding of the biology of pediatric hematological malignancies, however, its application to clinical care is still unclear. We present our experience integrating genomic data into the clinical management of children with high-risk hematologic malignancies and blood disorders and describe the broad impact that genomic profiling has in multiple aspects of patient care.The Precision in Pediatric Sequencing Program at Columbia University Medical Center instituted prospective clinical next-generation sequencing (NGS) for high-risk malignancies and blood disorders. Testing included cancer whole exome sequencing (WES) of matched tumor-normal samples or targeted sequencing of 467 cancer-associated genes, when sample adequacy was a concern, and tumor transcriptome (RNA-seq). A multidisciplinary molecular tumor board conducted interpretation of results and final tiered reports were transmitted to the electronic medical record according to patient preferences.Sixty-nine samples from 56 patients with high-risk hematologic malignancies and blood disorders were sequenced. Patients carried diagnoses of myeloid malignancy (n = 25), lymphoid malignancy (n = 25), or histiocytic disorder (n = 6). Six patients had only constitutional WES, performed for a suspicion of an inherited predisposition for their disease. For the remaining 50 patients, tumor was sequenced with matched normal tissue when available. The mean number of somatic variants per sample was low across the different disease categories (2.85 variants/sample). Interestingly, a gene fusion was identified by RNA-seq in 58% of samples who had adequate RNA available for testing. Molecular profiling of tumor tissue led to clinically impactful findings in 90% of patients. Forty patients (80%) had at least one targetable gene variant or fusion identified in their tumor tissue; however, only seven received targeted therapy. Importantly, NGS findings contributed to the refinement of diagnosis and prognosis for 34% of patients. Known or likely pathogenic germline alterations were discovered in 24% of patients involving cancer predisposition genes in 12% of cases.Incorporating whole exome and transcriptome profiling of tumor and normal tissue into clinical practice is feasible, and the value that comprehensive testing provides extends beyond the ability to target-specific mutations.
View details for DOI 10.3389/fped.2017.00265
View details for Web of Science ID 000417730800001
View details for PubMedID 29312904
View details for PubMedCentralID PMC5732960