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Pediatric blood & cancer  2013;61(4):729-736.
Therapy for childhood acute myeloid leukemia (AML) has historically included chemotherapy with or without autologous bone marrow transplant (autoBMT) or allogeneic hematopoietic stem cell transplantation (alloBMT). We sought to compare health-related quality-of-life (HRQOL) outcomes between these treatment groups.
Five-year survivors of AML diagnosed before age 21 and enrolled and treated from 1979 to 1995 on one of 4 national protocols were interviewed. These survivors or proxy caregivers completed a health questionnaire and an HRQOL measure.
Of 180 survivors, 100 were treated with chemotherapy only, 26 with chemotherapy followed by autoBMT, and 54 with chemotherapy followed by alloBMT. Median age at interview was 20 years (range 8 to 39). Twenty-one percent reported a severe or life-threatening chronic health condition (chemotherapy-only 16% vs. autoBMT 21% vs. alloBMT 33%; p=0.02 for chemotherapy-only vs. alloBMT). Nearly all (95%) reported excellent, very good or good health. Reports of cancer-related pain and anxiety did not vary between groups. HRQOL scores among 136 participants ≥ 14 years of age were similar among groups and to the normative population, though alloBMT survivors had a lower physical mean summary score (49.1 alloBMT vs. 52.2 chemotherapy-only; p=0.03). Multivariate analyses showed the presence of severe chronic health conditions to be a strong predictor of physical but not mental mean summary scores.
Overall HRQOL scores were similar among treatment groups, although survivors reporting more health conditions or cancer-related pain had diminished HRQOL. Attention to chronic health conditions and management of cancer-related pain may improve QOL.
PMCID: PMC4190066  PMID: 24285698
pediatric; bone marrow transplantation; acute myeloid leukemia; late effects; chronic health condition; quality of life
3.  Ovarian sex cord -stromal tumors, pleuropulmonary blastoma and DICER1 mutations: A report from the International Pleuropulmonary blastoma Registry 
Gynecologic oncology  2011;122(2):246-250.
Pleuropulmonary blastoma (PPB) is a childhood cancer arising from pleuropulmonary mesenchyme. This neoplasm is a sentinel disease in a familial tumor syndrome recently found to be associated with germline mutations in DICER1. Observations of ovarian sex cord-stromal tumors (OSCST) in PPB kindreds led to further study. We sought to characterize ovarian tumors seen in probands and families with PPB and PPB-related conditions and define germline DICER1 status.
Patient and family records of pathology-reviewed PPB cases enrolled in the International PPB Registry (IPPBR) were searched for ovarian tumors. Ovarian tumor pathology specimens were obtained and centrally-reviewed. Germline DNA from patients with ovarian tumors was tested for DICER1 mutations. Three additional OSCST patients registered in the IPPBR were also tested for mutations in DICER1.
Among 296 kindreds including 325 children with PPB, we observed 3 children with both PPB and Sertoli-Leydig cell tumors (SLCT)/Sertoli cell tumors. Among family members of PPB patients, we identified 6 OSCST (3 SLCT, 1 Sertoli cell tumor, 1 juvenile granulosa cell tumor, 1 gynandroblastoma). Age at ovarian tumor diagnosis was youngest in PPB probands and younger in family members than in OSCST in general. Germline DICER1 mutations were identified in 4 of 6 patients with OSCST from PPB kindreds and in 2 of 3 children with OSCST and no personal or family history of PPB.
Primary ovarian neoplasms, particularly OSCST, are a manifestation of the familial PPB syndrome and may be the initial clinical presentation of DICER1 mutations within a family.
PMCID: PMC3138876  PMID: 21501861
sex cord-stromal tumors; ovary; cancer; DICER1
4.  Health and Risk Behaviors in Survivors of Childhood Acute Myeloid Leukemia: A Report From the Children’s Oncology Group 
Pediatric blood & cancer  2010;55(1):157-164.
Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks.
Participants were diagnosed with AML at <21 years of age and survived ≥5 years following diagnosis. All underwent chemotherapy alone or followed by autologous BMT (chemo ± autoBMT) or underwent allogeneic BMT (alloBMT) if an HLA-matched related donor was available. Survivors completed a health questionnaire and a Youth Risk Behavior Survey (YRBS).
Of eligible survivors, 117 were ≥18 years of age and completed a YRBS. Survivors were a mean age of 10 years at diagnosis and 24 years at interview. Of the substance exposures assessed by YRBS, tobacco, alcohol, and marijuana were most common. Twenty-two percent (22%) had smoked cigarettes in the last 30 days. One-quarter (25%) reported binge drinking in the last month. None of these exposures varied by treatment group. Less than 10% of survivors reported cocaine, heroin, or methamphetamine use. Men were more likely to report high substance exposure (P = 0.004). Sadness/suicidality score was associated with cancer-related anxiety (P = 0.006) and multiple health conditions (P = 0.006).
This analysis reveals exposure to tobacco, alcohol, and marijuana in young adults with few differences based on treatment received. Survivors with cancer-related anxiety or multiple health conditions were more likely to report sadness/hopelessness.
PMCID: PMC3152207  PMID: 20232426
leukemia; pediatric; smoking; survivor
5.  Judicious DICER1 Testing and Surveillance Imaging Facilitates Early Diagnosis and Cure of Pleuropulmonary blastoma 
Pediatric blood & cancer  2014;61(9):1695-1697.
Pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT) are both associated with germline mutations in DICER1. In this brief report, a maternal history of SLCT led to identification of a deleterious DICER1 mutation in the patient and her asymptomatic infant. Radiographic screening revealed a large Type I PPB which was completely resected. Identification of DICER1 mutation carriers and imaging of children at risk for PPB may allow detection of PPB in its earliest and most curable form, leading to increased likelihood of surgical cure and decreased risks of treatment-related late effects.
PMCID: PMC4139105  PMID: 24821309
Pleuropulmonary blastoma; DICER1; Sertoli-Leydig cell tumor; lung cysts; genetic testing
6.  Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor-predisposition disorder 
Human genetics  2014;133(11):1443-1450.
Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal tumor that typically presents in young children. We previously reported on NCMH occurrence in children with pleuropulmonary blastoma (PPB), a rare pulmonary dysembryonic sarcoma that is the hallmark neoplasm in the PPB-associated DICER1 tumor predisposition disorder.
Original pathologic materials from individuals with a PPB, PPB-associated tumor and/or a DICER1 mutation were centrally reviewed by the International PPB Registry. Paraffin-embedded NCMH tumor tissue was available in three cases. Laser-capture microdissection was used to isolate mesenchymal spindle cells and cartilage in one case for Sanger sequencing of DICER1.
Nine patients (5F/4M) had PPB and NCMH. NCMH was diagnosed at a median age of 10 years (range 6-21years). NCMH developed 4.5 - 13 years after PPB. Presenting NCMH symptoms included chronic sinusitis and nasal congestion. Five patients had bilateral tumors. Local NCMH recurrences required several surgical resections in two patients, but all nine patients were alive at 0 – 16 years of follow-up. Pathogenic germline DICER1 mutations were found in 6/8 NCMH patients tested. In 2 of the patients with germline DICER1 mutations, somatic DICER1 missense mutations were also identified in their NCMH (E1813D; n=2). Three additional PPB patients developed other nasal lesions seen in the general population (a Schneiderian papilloma, chronic sinusitis with cysts, and allergic nasal polyps with eosinophils). Two of these patients had germline DICER1 mutations.
Pathogenic germline and somatic mutations of DICER1 in NCMH establishes that the genetic etiology of NCMH is similar to PPB, despite the disparate biological potential of these neoplasms.
PMCID: PMC4185226  PMID: 25118636
Nasal chondromesenchymal hamartoma; DICER1; Pleuropulmonary blastoma

Results 1-6 (6)