Research Summary
My areas of interest include Sickle cell disease and Rare Tumors especially germ cell tumors and infrequent cancers. In sickle cell disease, my focus has been on studying the prevalence, risk factors and potential treatment options for pulmonary hypertension in children with sickle cell disease.

In oncology, my research activities have focused on collaborative studies through the Children's Oncology Group in germ cell tumors and infrequent cancers. I am the Chair of the Infrequent tumor Subcommittee at COG. We developed and published guidelines for several rare tumors and have recently completed two international clinical trials, on adrenocortical carcinoma and nasoparyngeal carcinoma. I am a member of the Malignant Germ Cell Tumor International Collaborative. Through this collaborative, we have merged 25 years of clinical trial data from US and UK pediatric and adult germ cell clinical trials. This has helped us redefine risk stratification and conduct several analyses. I took leadership of analyzing the data on ovarian immature teratomas. Ovarian immature teratomas are a rare malignancy. There is significant difference in treatment approach between the adult and pediatric groups. In pediatrics, patients are primarily treated with surgery alone, whereas adults receive chemotherapy for all ovarian IT, except Stage I, grade 1 patientsI analyzed the pediatric and adult clinical trial data, and found that grade was the most important risk factor for relapse. More importantly, I found that despite a wide difference in treatment approaches, between adults and pediatrics, the outcomes were similar, bringing up the question of the necessity of adjuvant chemotherapy for ovarian IT.

Specialized Terms: Clinical trials in Pediatric Oncology; Sickle cell anemia

Extensive Research Description
1. Sickle Cell Disease

Pulmonary hypertension occurs in one third of adults with SCD disease and is an independent risk factor for mortality. There was limited data in children. I thus designed a prospective screening study. This study identified that elevated pulmonary artery pressures (PAP) occurs in 30% of children, and is associated with hypoxia, hemolysis and a high platelete count. This was the first prospective screening study in children, and showed that similar to adults, children develop elevated PAP. This was published in Pediatrics, and has been widely quoted.

Our screening study showed that children develop elevated PAP. However there was no data on the long term outcome and possible reversibility of this complication. I designed a single institution pilot study to determine if treatment with Hydroxyurea, an antihemolytic agent could reverse elevated PAP in children. This study showed that elevated PAP was reversible with hydroxyurea, and was published in British Journal of Hematology. Due to the exciting results from our single center pilot, we secured CTSA funding and conducting a multicenter study. This study was limited by sample size, and showed a trend towards decrease in PAP with hydroxyurea. The study did show that hydroxyurea improved oxygenation in SCD.

Working with a medical student, we looked at the association of nephropathy with elevated PAP, and found that elevated PAP was associated with early signs of nephropathy, in form of proteinuria. This was the first study describing this association, and was published.

Current Studies and Future Direction

1. We have an ongoing longitudinal follow up study of elevated PAP in children with SCD. This study will help us determine if children with elevated PAP, develop the irreversible PHT in adults.

2. Emotional Intelligence and Health Related Quality of Life Outcomes in Children with Sickle Cell Anemia.

3.Prevalence and Progression of Retinopathy in children with Sickle Cell Disease

4. Sickle Cell Nepal- A Pilot research and education project for sickle cell disease in Western

2. Rare Tumors

I am the chair of the Infrequent Tumor Subcommittee at COG. We developed and published guidelines for several rare tumors and have recently completed two international clinical trials, on adrenocortical carcinoma and nasoparyngeal carcinoma.

3. Germ Cell Tumors

1 am a member of the Malignant Germ Cell Tumor International Collaborative. Through this collaborative, we have merged 25 years of clinical trial data from US and UK pediatric and adult germ cell clinical trials. This has helped us redefine risk stratification and conduct several analyses. I took leadership of analyzing the data on ovarian immature teratomas. Ovarian immature teratomas are a rare malignancy. There is significant difference in treatment approach between the adult and pediatric groups. In pediatrics, patients are primarily treated with surgery alone, whereas adults receive chemotherapy for all ovarian IT, except Stage I, grade 1 patients

I analyzed the pediatric and adult clinical trial data, and found that grade was the most important risk factor for relapse. More importantly, I found that despite a wide difference in treatment approaches, between adults and pediatrics, the outcomes were similar, bringing up the question of the necessity of adjuvant chemotherapy for ovarian IT.

This paper has been accepted in Cancer

Future direction: In the soon to be opened low/intermediate risk germ cell trial, all pediatric and adult patients with ovarian IT will be observed.



Research Interests
Anemia, Sickle Cell; Echocardiography; Hematology; Hypertension, Pulmonary; Medical Oncology; Pediatrics