- Pediatric Hematology-Oncology
- Relapsed leukemia
- Infectious complication of oncology treatment
- Fungal infections
Honors & Awards
AOA, Medical Honor Society (2007)
Fellow, Rachleff Hem-Onc Pediatric Fellowship fund (2012-2013)
Medical Education: Tufts University School of Medicine (2007) MA
Fellowship: Stanford University Pediatric Hematology Oncology Fellowship (2014) CA
Residency: Mass General Hospital for Children Pediatric Residency (2011) MA
Internship: Mass General Hospital for Children Pediatric Residency (2008) MA
Board Certification: American Board of Pediatrics, Pediatrics (2010)
Board Certification: American Board of Pediatrics, Pediatric Hematology-Oncology (2015)
Chief Resident, Massachusetts General Hospital for Children, Pediatrics (2011)
Resident, Massachusetts General Hospital for Children, Pediatrics (2010)
Doctor of Medicine, Tufts University School of Medicine (2007)
Current Research and Scholarly Interests
I am interested in the prevention and management of infectious complication in pediatric oncology patients. I am also interested in developing a protocol for the management of low risk patients with fever and neutropenia.
Home Away From Home - Quality of Life Surveys
Treatment for pediatric acute myeloid leukemia (AML) involves intensive chemotherapy regimens that result in periods of profound neutropenia leaving patients susceptible to severe infectious complications. Infectious complications are the leading cause of treatment related mortality among AML patients, but there are little clinical data to inform whether management of neutropenia post AML chemotherapy should occur in an outpatient or inpatient setting. Further, no studies have been conducted that assess the impact of neutropenia management strategy on the quality of life of pediatric patients with AML and their caregivers.
Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold Infections
This study will establish a non-invasive diagnostic approach and evaluate clinical outcomes for children at high-risk for pulmonary invasive mold infection (PIMI).
Phase I Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies
This phase I trial studies the best dose and side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating children or young adults with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating children or young adults with B acute lymphoblastic leukemia.
A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric participants with relapsed/refractory acute lymphoblastic leukemia (ALL) or relapsed/refractory lymphoblastic lymphoma. A safety expansion cohort of approximately 20 patients may be enrolled in addition to the 50 participants in dose-escalation cohort.
Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.
Medical Outcomes, Quality of Life, and Family Perceptions for Outpatient vs Inpatient Neutropenia Management After Chemotherapy for Pediatric Acute Myeloid Leukemia.
JAMA network open
2021; 4 (10): e2128385
Importance: Pediatric acute myeloid leukemia (AML) requires multiple courses of intensive chemotherapy that result in neutropenia, with significant risk for infectious complications. Supportive care guidelines recommend hospitalization until neutrophil recovery. However, there are little data to support inpatient over outpatient management.Objective: To evaluate outpatient vs inpatient neutropenia management for pediatric AML.Design, Setting, and Participants: This cohort study used qualitative and quantitative methods to compare medical outcomes, patient health-related quality of life (HRQOL), and patient and family perceptions between outpatient and inpatient neutropenia management. The study included patients from 17 US pediatric hospitals with frontline chemotherapy start dates ranging from January 2011 to July 2019, although the specific date ranges differed for the individual analyses by design and relative timing. Data were analyzed from August 2019 to February 2020.Exposures: Discharge to outpatient vs inpatient neutropenia management.Main Outcomes and Measures: The primary outcomes of interest were course-specific bacteremia incidence, times to next course, and patient HRQOL. Course-specific mortality was a secondary medical outcome.Results: Primary quantitative analyses included 554 patients (272 [49.1%] girls and 282 [50.9%] boys; mean [SD] age, 8.2 [6.1] years). Bacteremia incidence was not significantly different during outpatient vs inpatient management (67 courses [23.8%] vs 265 courses [29.0%]; adjusted rate ratio, 0.73; 95% CI, 0.56 to 1.06; P=.08). Outpatient management was not associated with delays to the next course compared with inpatient management (mean [SD] 30.7 [12.2] days vs 32.8 [9.7] days; adjusted mean difference, -2.2; 95% CI, -4.1 to -0.2, P=.03). Mortality during intensification II was higher for patients who received outpatient management compared with those who received inpatient management (3 patients [5.4%] vs 1 patient [0.5%]; P=.03), but comparable with inpatient management at other courses (eg, 0 patients vs 5 patients [1.3%] during induction I; P=.59). Among 97 patients evaluated for HRQOL, outcomes did not differ between outpatient and inpatient management (mean [SD] Pediatric Quality of Life Inventory total score, 70.1 [18.9] vs 68.7 [19.4]; adjusted mean difference, -2.8; 95% CI, -11.2 to 5.6). A total of 86 respondents (20 [23.3%] in outpatient management, 66 [76.7%] in inpatient management) completed qualitative interviews. Independent of management strategy received, 74 respondents (86.0%) expressed satisfaction with their experience. Concerns for hospital-associated infections among caregivers (6 of 7 caregiver respondents [85.7%] who were dissatisfied with inpatient management) and family separation (2 of 2 patient respondents [100%] who were dissatisfied with inpatient management) drove dissatisfaction with inpatient management. Stress of caring for a neutropenic child at home (3 of 3 respondents [100%] who were dissatisfied with outpatient management) drove dissatisfaction with outpatient management.Conclusions and Relevance: This cohort study found that outpatient neutropenia management was not associated with higher bacteremia incidence, treatment delays, or worse HRQOL compared with inpatient neutropenia management among pediatric patients with AML. While outpatient management may be safe for many patients, course-specific mortality differences suggest that outpatient management in intensification II should be approached with caution. Patient and family experiences varied, suggesting that outpatient management may be preferred by some but may not be feasible for all families. Further studies to refine and standardize safe outpatient management practices are warranted.
View details for DOI 10.1001/jamanetworkopen.2021.28385
View details for PubMedID 34709389
Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.
Journal of the Pediatric Infectious Diseases Society
BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis.METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups.RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days.CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents.CLINICAL TRIALS REGISTRATION: NCT01869829.
View details for DOI 10.1093/jpids/piab024
View details for PubMedID 34374424
Systematic Review of Approaches to Preserve Machine Learning Performance in the Presence of Temporal Dataset Shift in Clinical Medicine.
Applied clinical informatics
2021; 12 (4): 808-815
OBJECTIVE: The change in performance of machine learning models over time as a result of temporal dataset shift is a barrier to machine learning-derived models facilitating decision-making in clinical practice. Our aim was to describe technical procedures used to preserve the performance of machine learning models in the presence of temporal dataset shifts.METHODS: Studies were included if they were fully published articles that used machine learning and implemented a procedure to mitigate the effects of temporal dataset shift in a clinical setting. We described how dataset shift was measured, the procedures used to preserve model performance, and their effects.RESULTS: Of 4,457 potentially relevant publications identified, 15 were included. The impact of temporal dataset shift was primarily quantified using changes, usually deterioration, in calibration or discrimination. Calibration deterioration was more common (n=11) than discrimination deterioration (n=3). Mitigation strategies were categorized as model level or feature level. Model-level approaches (n=15) were more common than feature-level approaches (n=2), with the most common approaches being model refitting (n=12), probability calibration (n=7), model updating (n=6), and model selection (n=6). In general, all mitigation strategies were successful at preserving calibration but not uniformly successful in preserving discrimination.CONCLUSION: There was limited research in preserving the performance of machine learning models in the presence of temporal dataset shift in clinical medicine. Future research could focus on the impact of dataset shift on clinical decision making, benchmark the mitigation strategies on a wider range of datasets and tasks, and identify optimal strategies for specific settings.
View details for DOI 10.1055/s-0041-1735184
View details for PubMedID 34470057
Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.
2020; Online ahead of print
Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found this disease to be highly diverse in presentation and overall outcome. Moreover, we discovered somatically-acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish somatic CBL patients from germline CBL patients, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among germline CBL patients. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.
View details for DOI 10.3324/haematol.2020.270595
View details for PubMedID 33375775
Paraneoplastic Neurologic Symptoms in a Pediatric Patient with Hodgkin Lymphoma.
Neurological paraneoplastic syndromes are exceedingly rare, and often difficult to recognize clinically. Paraneoplastic achalasia is a condition characterized by new onset dysphagia that is unrelated to tumor burden, most often due to the development of auto-immune antibodies targeting esophageal tissue. Due to the rarity of this condition, diagnosis is often delayed, leading to increased time to treatment. Here we report a case of a rare paraneoplastic achalasia in a female child with EBV+Hodgkin lymphoma, review literature describing paraneoplastic achalasia, and discuss treatment strategies for improving clinical outcome in these patients.
View details for DOI 10.1080/07357907.2020.1852412
View details for PubMedID 33191790
- Summary of COVID-19 clinical practice adjustments across select institutions PEDIATRIC BLOOD & CANCER 2020
- Summary of COVID-19 clinical practice adjustments across select institutions. Pediatric blood & cancer 2020: e28411
CONTINUATION OF TYROSINE KINASE INHIBITORS AFTER CHEMOTHERAPY IN PH plus ACUTE LYMPHOBLASTIC LEUKEMIA
View details for Web of Science ID 000490282100037
Mucormycosis diagnosed during induction chemotherapy in five pediatric patients with acute lymphoblastic leukemia.
Pediatric blood & cancer
Mucormycosis in pediatric oncology patients is a rare invasive fungal infection associated with significant morbidity and mortality. We describe five patients diagnosed with mucormycosis during induction chemotherapy for acute lymphoblastic leukemia at our institution. All of the patients in our series survived, some in spite of having disseminated disease. Most of the patients' chemotherapy was modified with the aim of controlling their leukemia while minimizing immunosuppression until their fungal infection was under control. Although mucormycosis is frequently fatal, rapid diagnosis and a multidisciplinary approach can lead to excellent outcomes, even in patients undergoing intensive chemotherapy.
View details for DOI 10.1002/pbc.27834
View details for PubMedID 31131954
- Comparison of the Transcriptomic Signature of Pediatric Vs. Adult CML and Normal Bone Marrow Stem Cells AMER SOC HEMATOLOGY. 2018
- Chromation Remodeling Therapy and Capizzi Methotrexate in Treatment-Related MDS/AML AMER SOC HEMATOLOGY. 2018
- Identifying patient- and family-centered outcomes relevant to inpatient versus at-home management of neutropenia in children with acute myeloid leukemia PEDIATRIC BLOOD & CANCER 2018; 65 (4)
Identifying patient- and family-centered outcomes relevant to inpatient versus at-home management of neutropenia in children with acute myeloid leukemia.
Pediatric blood & cancer
2018; 65 (4)
Efficacy of therapeutic strategies relative to patient- and family-centered outcomes in pediatric oncology must be assessed. We sought to identify outcomes important to children with acute myeloid leukemia and their families related to inpatient versus at-home management of neutropenia. We conducted qualitative interviews with 32 children ≥8 years old and 54 parents. Analysis revealed the impact of neutropenia management strategy on siblings, parent anxiety, and child sleep quality as being outcomes of concern across respondents. These themes were used to inform the design of a questionnaire that is currently being used in a prospective, multiinstitutional comparative effectiveness trial.
View details for PubMedID 29286570
Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.
Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness.A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables.From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI.The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017. © 2017 American Cancer Society.
View details for DOI 10.1002/cncr.30792
View details for PubMedID 28542918
Pediatric Oncology Discharges With Febrile Neutropenia: Variation in Location of Care
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
2017; 39 (1): E1-E7
We examined the use of Pediatric Cancer Specialty Centers (PCSCs) over time and the length of stay (LOS) in pediatric oncology patients with a diagnosis of febrile neutropenia. PCSCs were defined as Children's Oncology Group and California Children's Services designated centers. We performed a retrospective analysis on all discharges of pediatric (0 to 18) oncology patients with febrile neutropenia in California (1983 to 2011) using the private Office of Statewide Health Planning and Development database. We examined influence of age, sex, race/ethnicity, payer, income, distance, tumor type, and complications on utilization of PCSCs and LOS (SAS 9.2). Analysis of 24,559 pediatric oncology febrile neutropenia discharges showed hospitalizations in PCSCs increasing from 48% in 1983 to 94% in 2011. The adjusted regression analysis showed decreased PCSC utilization for ages 15 to 18, Hispanic patients, and those living >40 miles away. The median PCSC LOS was 9 days compared with 7 days at a non-PCSC (P<0.0001). Discharge from a PCSC was associated with a LOS >8 days after controlling for complications. Inpatient PCSC care for febrile neutropenia in California has increased since 1983. Receiving care at a PCSC is influenced by age, tumor type, ethnicity, geography, and complications.
View details for DOI 10.1097/MPH.0000000000000716
View details for Web of Science ID 000391634100001
View details for PubMedID 27918351
Invasive Fungal Disease in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
2016; 38 (7): 574-580
View details for Web of Science ID 000385523700029
Invasive Fungal Disease in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant.
Journal of pediatric hematology/oncology
2016; 38 (7): 574–80
Invasive fungal disease (IFD) remains a major cause of morbidity and mortality in pediatric patients after allogeneic hematopoietic stem cell transplant (HSCT). We analyzed the outcome of 152 consecutive pediatric patients who underwent allogeneic HSCT from 2005 to 2012: 126 of these without a history of IFD and 26 with IFD before HSCT. Antifungal prophylaxis agent was determined by the primary transplant attending. The rate of IFD after HSCT among patients with or without prior IFD was similar (7.7% with and 7.1% without a history of fungal disease before transplant). Mortality in these 2 populations did not differ (35% vs. 28%, P=0.48, χ). Patients deemed at higher risk for IFD were generally placed on voriconazole prophylaxis; however, this did not affect rates of posttransplant IFD. All-cause mortality in patients with posttransplant IFD was significantly higher than those without posttransplant IFD (67% vs. 21%, P<0.0001,χ). Identifying risk factors for posttransplant IFD remains a high priority to improve outcome of HSCT.
View details for PubMedID 27658021
Evaluation of Febrile, Nonneutropenic Pediatric Oncology Patients with Central Venous Catheters Who Are Not Given Empiric Antibiotics
JOURNAL OF PEDIATRICS
2015; 166 (1): 157-162
To evaluate the practice of empiric antibiotics for febrile, nonneutropenic pediatric oncology patients with a central venous catheter (CVC) in place.Episodes of fever without neutropenia (absolute neutrophil count [ANC] ≥500 cells/mm(3)) were reviewed retrospectively in pediatric oncology patients with a CVC undergoing chemotherapy. Characteristics and symptoms were compared between patients with bacteremia and patients without bacteremia.A total of 392 episodes of nonneutropenic fever in 138 subjects (52 females; 38%) were reviewed. In this cohort, the median age at an episode was 7 years, and the majority of patients had a diagnosis of acute leukemia (54%). Median ANC was 3100 cells/mm(3) (IQR, 1570-5980 cells/mm(3)). Median temperature was 38.7°C (IQR, 38.3-39.2°C). Twenty-four infectious episodes (6%) occurred in 18 subjects, and 5 CVCs required removal; all patients requiring removal admitted and received antibiotics owing to chills. There were no significant difference in age, sex, or ANC between patients with bacteremia and those without bacteremia; however, mean temperature was higher in the patients with bacteremia (39.4°C vs 38.7°C; P = .003). No deaths due to sepsis occurred, and no CVCs were removed because antibiotics were not administered empirically.Our practice of observing pediatric oncology patients undergoing chemotherapy with CVCs who are not neutropenic does not appear to lead to increased serious adverse outcomes and avoids antibiotic exposure for >90% of patients without a bacterial infection.
View details for DOI 10.1016/j.jpeds.2014.09.008
View details for PubMedID 25444524
The Neutropenic Diet ... Still Ageless? C. Aftandilian Article Reviewed
2012; 26 (6): 586-589
View details for Web of Science ID 000305794100012
The neutropenic diet... still ageless?
Oncology (Williston Park, N.Y.)
2012; 26 (6): 586-?
View details for PubMedID 22870544
Burkitt Lymphoma With Pancreatic Involvement
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
2010; 32 (8): E338-E340
A 10-year-old boy was referred to our clinic for tonsillectomy and was found to have a large mass within his oropharynx. Intraoperative biopsies confirmed Burkitt lymphoma. Further imaging and biopsy revealed pancreatic involvement. He was treated with multiagent chemotherapy. He remains disease-free 6 years later. Review of the literature demonstrates other cases of non-Hodgkin lymphoma with pancreatic involvement with good outcomes. Pancreatic involvement is a relatively rare occurrence in childhood lymphoma.
View details for DOI 10.1097/MPH.0b013e3181ed1178
View details for Web of Science ID 000283538300021
View details for PubMedID 20930650
Group therapy for substance use disorders: What do we know?
HARVARD REVIEW OF PSYCHIATRY
2004; 12 (6): 339-350
Although group therapy is the most prevalent treatment modality for substance use disorders, an up-to-date review of treatment outcome literature does not exist. A search of the literature yielded 24 treatment outcome studies comparing group therapy to other treatment conditions. These studies fell into one of six research design categories: (1) group therapy versus no group therapy; (2) group therapy versus individual therapy; (3) group therapy plus individual therapy versus group therapy alone; (4) group therapy plus individual therapy versus individual therapy alone; (5) group therapy versus another group therapy with different content or theoretical orientation; and (6) more group therapy versus less group therapy. In general, treatment outcome studies did not demonstrate differences between group and individual modalities, and no single type of group therapy reliably demonstrated greater efficacy than others. Unique methodological and logistical hurdles encountered in research on group therapy for substance use disorders, as well as considerations for future research, are also discussed.
View details for DOI 10.1080/1067322049095723
View details for Web of Science ID 000226593100004
View details for PubMedID 15764469
Requiring remission of undue influence of weight and shape on self-evaluation in the definition of recovery for bulimia nervosa
Annual Conference of the Academy-for-Eating-Disorders
JOHN WILEY & SONS INC. 2003: 200–210
The current study evaluated the concurrent validity of requiring remission of undue influence of weight and shape on self-evaluation (undue influence) in defining recovery from bulimia nervosa (BN).Three groups completed the Beck Depression Inventory, the Mood and Anxiety Symptom Questionnaire, the Body Shape Questionnaire, and the Social Adjustment Scale: 31 women were fully recovered from BN (FR), 28 women had no behavioral symptoms of BN (partially recovered [PR]), and 59 matched non-eating-disordered controls (MC).The PR group had more pathologic scores on depression, anxiety, body dissatisfaction, and social adjustment compared with both the FR and MC groups, which did not differ from each other.These findings suggest that including remission of cognitive symptoms in a standardized definition of recovery may prove to be clinically useful in establishing reliable prognostic indicators. Future research should evaluate the role played by cognitive symptoms in triggering relapse.
View details for DOI 10.1002/eat.10187
View details for Web of Science ID 000184510900003
View details for PubMedID 12898556