Anne Angiolillo

George Washington University, Washington, Washington, D.C., United States

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Publications (18)85.86 Total impact

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    ABSTRACT: Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 10/2014;
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    ABSTRACT: Purpose: High-throughput sequencing (HTS) of immunoglobulin heavy chain genes (IGH) in unselected clinical samples for minimal residual disease (MRD) in B lymphoblastic leukemia (B-ALL) has not been tested. As current methods for MRD detection, such as flow cytometry or patient-specific qPCR are complex or difficult to standardize in the clinical laboratory, sequencing may enhance clinical prognostication. Experimental design: We sequenced IGH in paired pre- and day 29 post-treatment samples using residual material from consecutive, unselected samples from Children's Oncology Group AALL0932 trial to measure MRD as compared to flow cytometry. We assessed the impact of on-going recombination at IGH on MRD detection in post-treatment samples. Lastly, we evaluated a subset of cases with discordant MRD results between flow cytometry and sequencing. Results: We find clonal IGH rearrangements in 92 of 98 pre-treatment patient samples. Further, while on-going recombination of IGH was evident, index clones typically prevailed in MRD-positive post-treatment samples, suggesting that clonal evolution at IGH does not contribute substantively to tumor fitness. MRD was detected by sequencing in all flow cytometry positive cases with no false negative results. Additionally, in a subset of patients, MRD was detected by sequencing, but not by flow cytometry, including a fraction with MRD levels within the sensitivity of flow cytometry. We provide data that suggest that this discordance in some patients may be due to the phenotypic maturation of the transformed cell. Conclusion: Our results provide strong support for high-throughput sequencing of IGH to enhance clinical prognostication in B-ALL.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 06/2014;
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    ABSTRACT: Children's Cancer Group-1991 selected 2 components from the Children's Cancer Group studies shown to be effective in high-risk acute lymphoblastic leukemia and examined them in children with National Cancer Institute standard-risk acute B-precursor lymphoblastic leukemia. These were (1) vincristine and escalating IV methotrexate (MTX) without leucovorin rescue during the interim maintenance (IM) phases and (2) addition of a second delayed intensification (DI) phase. Eligible patients (n = 2078) were randomly assigned to regimens containing either oral (PO) MTX, PO mercaptopurine, dexamethasone, and vincristine or IV MTX during IM phases, and regimens with either single DI or double DI. Five-year event-free survival (EFS) and overall survival for patients on the PO MTX arms were 88.7% ± 1.4% and 96% ± 0.9% versus 92.6% ± 1.2% and 96.5% ± 0.8% for those on the IV MTX arms (P = .009, P = .66). Five-year EFS and overall survival for patients who received single DI were 90.9% ± 1.3% and 97.1% ± 0.8% versus 90.5% ± 1.3% and 95.4% ± 3.8% for those who received double DI (P = .71, P = .12). No advantage was found for a second DI; however, replacement of PO MTX, PO mercaptopurine, vincristine, and dexamethasone during IM with vincristine and escalating IV MTX improved EFS.
    Blood 05/2011; 118(2):243-51. · 9.78 Impact Factor
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    ABSTRACT: Because of the life-altering and potentially lingering psychosocial effects of leukemia on children and families, pediatric health professionals have developed a variety of interventions to mitigate family distress. Psychosocial health services are psychological and social services and interventions that enable patients, their families, and health care providers to optimize biomedical health care and to manage the psychological/behavioral and social aspects of illness and its consequences so as to promote better health (IOM 2008). Interventions are shaped by, informed by, and/or delivered by psychologists, psychiatrists, social workers, nurses, and chaplains, as well as by oncology subspecialists, ethicists, patients and their families, and advocacy organizations (Holland 2003). These interventions vary in their target population (patients, siblings, and/or parents and other family caregivers), settings, and characteristics. For example, a recent review of psychosocial health services for cancer patients and their families by the United States Institute of Medicine (IOM) found some interventions that were derived from a theoretical framework, some that were based on research evidence, and some that had undergone empirical testing; few evidenced all three characteristics (IOM 2008). Nevertheless, the IOM identified five common elements of models for the effective delivery of psychosocial health services: (1) identifying psychosocial health needs, (2) connecting patients and families to needed services, (3) supporting them in managing the illness, (4) coordinating psychosocial care with biomedical care, and (5) following up on care delivery to evaluate the effectiveness of these services (Fineberg 2008).
    12/2010: pages 285-301;
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    ABSTRACT: This study was conducted to gather pediatric oncologists' opinions about and suggestions for improvement of informed consent (IC) in pediatric phase 1 cancer trials. A questionnaire designed to elicit perspectives was distributed to 146 physicians at 6 participating institutions. A total of 103 completed surveys were returned for a 71% response rate. Pediatric oncologists believe providing information so families can decide about phase 1 study entry is the most important goal of the IC process (ICP). The majority of physicians (64%) report that they describe the phase 1 study without any attempt to influence parents' decisions. Several answers provided by physicians were associated with their gender and prior IC training. Male physicians were significantly more likely to endorse the no-attempt-to-influence approach, whereas female physicians were more likely to suggest to parents that other children will benefit from what is learned in phase 1 studies. Responses to an open-ended question provided 63 suggestions for improvement of the ICP, including document and training changes and tools to enhance physician-family communication. Pediatric oncologists tended to present phase 1 trials as an option rather than a strong recommendation and were reluctant to influence decisions of families about these studies. They believe most but not all parents understand key concepts involved in consent to this type of research, and had ample suggestions for how to improve the ICP. Future research and education efforts around this ethically challenging topic were warranted.
    Cancer 07/2010; 116(13):3244-50. · 5.20 Impact Factor
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    ABSTRACT: Despite the increasing cure rates for children with acute lymphoblastic leukemia (ALL), patients who relapse continue to have poor prognosis. The Children's Oncology Group (COG) conducted a limited institution Phase II trial of Campath-1H, a monoclonal antibody that targets CD52 on leukemic cells, in children with relapsed or refractory ALL. From October 2005 to December 2006, 13 eligible patients were enrolled on the COG phase II study of Campath-1H (ADVL0222). Campath-1H was initially administered as an intravenous infusion over 2 hr, five times per week for 1 week, then three times per week for three additional weeks. Patients with stable disease or better on day 29 could continue on to combination therapy with Campath-1H, methotrexate, and 6-mercaptopurine for two additional cycles. One of 13 patients enrolled had a complete response to Campath-1H and 4 had stable disease. Dose limiting toxicity occurred in two out of nine fully evaluable patients (Grade IV pain and Grade III allergic reaction/hypersensitivity). No patients received combination therapy. Serum Campath-1H concentrations appeared to be somewhat lower in children with ALL compared with adult patients with chronic lymphocytic leukemia. Although a single complete response was observed, activity of single agent Campath-1H appears limited. Our study does not support future single agent evaluation of Campath-1H in children with relapsed ALL.
    Pediatric Blood & Cancer 08/2009; 53(6):978-83. · 2.35 Impact Factor
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    ABSTRACT: Preclinical testing suggests the combination of carboplatin and irinotecan has at least additive antitumor activity. The primary objectives of the current study were to determine the maximum tolerated doses (MTDs) and recommended phase 2 doses of carboplatin administered with irinotecan to pediatric patients with refractory solid tumors. This was a multicenter, open-label, single-arm dose escalation study in which subjects with refractory solid tumors received 21-day treatment cycles of intravenous carboplatin on Day 1 followed by intravenous irinotecan administered daily for 10 days within 2 consecutive weeks. The plasma pharmacokinetics of ultrafiltrable platinum, irinotecan, and 2 irinotecan metabolites were determined during Cycle 1. The interpatient plan for dose escalation at study initiation was to increase irinotecan first followed by increases in carboplatin. Twenty-eight patients with a median age of 8.5 years (range, 1-21 years) were enrolled with a variety of solid tumors. Two of 6 subjects at the first dose level (carboplatin target area under the curve [AUC], 4.0 mg/mL*min; irinotecan, 18 mg/m2/dose) experienced dose-limiting gastrointestinal toxicities requiring a dose de-escalation scheme (carboplatin AUC, 4.0 mg/mL*min; irinotecan, 15 mg/m2/dose). Three of 6 subjects at the second dose level experienced dose-limiting gastrointestinal complications and bone marrow suppression. A further dose de-escalation to carboplatin AUC of 4.0 mg/mL*min and irinotecan of 12 mg/m2/dose resulted in dose-limiting bone marrow suppression in 1 of 13 patients treated at that dose, and therefore was determined to be the MTD. One complete response (in a patient with medulloblastoma) and 3 partial responses (in patients with neuroblastoma, medulloblastoma, and lymphoendothelial carcinoma, respectively) were observed. The recommended phase 2 dose in heavily pretreated pediatric patients is carboplatin (AUC, 4 mg/mL*min on Day 1) and irinotecan (12 mg/m2/dayx10 days) given every 21 days.
    Cancer 01/2009; 115(1):207-16. · 5.20 Impact Factor
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    ABSTRACT: Immunophenotypic analysis can identify protein epitopes in non-Hodgkin lymphomas (NHL) that may respond to targeted immunotherapies, such as anti-CD20 and anti-CD52. Recent studies suggest additional targets may provide therapeutic benefits in NHL. This study evaluated protein expression of CD25, CD52, CD74 and CD80 in paediatric NHL to determine possible targets for immune-based therapeutic approaches. Patient samples were derived from paediatric NHL clinical trials sponsored by the Children's Cancer Group (CCG, now the Children's Oncology Group, COG) and included Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), disseminated T- and B-cell lymphoblastic lymphoma (T-LBL and B-LBL) and anaplastic large cell (ALCL). Immunophenotypic studies were performed on formalin-fixed, paraffin-embedded diagnostic tissues. CD25 was expressed in 8% of T-LBL and 75% of ALCL cases, but not in BL, DLBCL, or B-LBL. CD52 was expressed in 99% of cases of paediatric NHL of all subtypes. CD74 was expressed in 100% of B-LBL, BL and DLBCL, but was absent in ALCL and T-LBL. CD80 was expressed in 12% of B-LBL, 6% of BL and 10% of DLBCL cases studied, but was not detected in T-cell NHL. These expression patterns suggest that CD25, CD52 and CD74 may represent potential new therapeutic targets in paediatric NHL.
    British Journal of Haematology 09/2007; 138(4):506-12. · 4.94 Impact Factor
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    ABSTRACT: The prognosis for children with recurrent CD20+ non-Hodgkin's lymphoma is dismal. A radiolabeled anti-CD20 antibody, 90yttrium-ibritumomab-tiuxetan (90Y-IT), is Food and Drug Administration approved for adults with recurrent indolent CD20+ B cell-non-Hodgkin's lymphoma. There is no data on the safety and feasibility of 90Y-IT in refractory childhood CD20+ lymphoma. Children and adolescents with refractory/relapsed CD20+ lymphoma were eligible for this phase I radioimmunotherapy study. Patients (n=5) received rituximab (250 mg/m2 i.v.) on days 0 and 7 and indium-111 ibritumomab-tiuxetan (5 mCi i.v.) on day 0. Dosimetry studies were done on days 0, 1, 3, and 6. Immediately after rituximab on day 7, patients received 90Y-IT if dosimetry studies showed<2000 cGy exposure to all solid organs and<300 cGy to marrow, as well as 0.4 mCi/kg in patients with good marrow reserve (n=3) and 0.1 mCi/kg in patients with poor marrow reserve (after bone marrow transplant; n=2). No patients experienced nonhematologic or hematologic dose-limiting toxicity. Human antimurine antibody/human antichimeric antibody incidence was 0%. One patient experienced grade II infusion-related chills associated with rituximab. The following are the means of organ radiation exposure (cGy): kidneys 341 (112-515), liver 345 (83-798), lungs 309 (155-519), marrow 46 (20-78), spleen 565 (161-816), and total body 42 (14-68). Based on these findings, an expanded investigator-initiated limited institutional phase II study has been designed to further evaluate the safety, tolerability, and response rate with 90Y-IT dose stratification based on marrow reserve.
    Clinical Cancer Research 09/2007; 13(18 Pt 2):5652s-5660s. · 7.84 Impact Factor
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    ABSTRACT: Oncologists in the US increasingly face the challenge of communicating with non-English speaking parents of children with cancer. This study explores this challenge from the perspectives of a sample of pediatric oncologists, interpreters, and Spanish-speaking parents of children with newly diagnosed leukemia. Thirty-seven oncologists and 17 professional language interpreters based at two non-profit pediatric hospitals in the US were surveyed on the topic of language barriers in pediatric care. Seventeen parents who communicated with their child's oncologist through an interpreter were also surveyed. All groups expressed considerable concern over the process of communicating across a language barrier. For oncologists, these concerns included the accuracy and completeness of interpretations, complexity of information, and loss of confidence and control over the communication process. For interpreters, they included complexity of information, information overload, and lack of clinician sensitivity toward the cultural and socioeconomic backgrounds of limited English proficiency (LEP) families. Parent concerns included difficulties comprehending information and anxiety over the possibility of missing out on important information. All groups provided multiple suggestions for improving communication across a language barrier. Oncologists, interpreters, and parents expressed considerable concern over the process of communicating across a language barrier. Some of these concerns could be minimized through efforts to boost interpreter accuracy and completeness, including the use of more simple, easy to understand language. Other issues, such as differences in culture and socioeconomic background, warrant consideration of the intercultural knowledge and skills of interpreters.
    Pediatric Blood & Cancer 12/2006; 47(6):819-24. · 2.35 Impact Factor
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    ABSTRACT: To group patients receiving treatment for acute lymphoblastic leukemia (ALL) according to their oral mercaptopurine (6-MP) metabolite levels and to establish cut-off points to screen for potential poor clinical outcome. Methodological study using 6-MP metabolite levels from 48 adolescent ALL patients enrolled in a multicenter adherence study. Cluster analysis was the primary analytical technique. We used two validation methods (a split-sampling and a simulation technique) for validating the results. Four clusters were retained in our initial analysis using our first group of patients (n = 27). Three clusters (labeled 1, 2, and 4) exhibited the expected negative correlation between the two metabolites, that is, "high" values of one were associated with "low" values of the other. One cluster (labeled 3) had "low" levels for both TGN and MMP. Five of the 27 adolescents had their 6-MP "held" during the study. Post-hoc examination of the results revealed that all five grouped in Cluster 3 during the time that their medications were stopped, but grouped in other clusters at other times. The median ANC was highest in Cluster 3, consistent with low therapeutic drug levels. Parameters were reproducible with both validation methods. Values below the respective 75th centile for both TGN and MMP in Cluster 3 for the complete sample (n = 48) are suggested as representing a potentially higher risk for relapse. This study provides an objective method for identifying patients at risk for treatment failure due to suboptimal 6-MP therapy; the clinical significance of this approach should be examined in future studies.
    Pediatric Blood & Cancer 03/2006; 46(2):187-92. · 2.35 Impact Factor
  • Anne L Angiolillo, J Whitlock, Z Chen, M Krailo, G Reaman
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    ABSTRACT: To determine the response rate and toxicity to gemcitabine administered as 10 mg/m2/min x 360 min weekly for 3 weeks in children with relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). Gemcitabine is a deoxycytidine analog that inhibits DNA synthesis and repair and has a broad spectrum of antitumor activity. From April 2001 to April 2003, 23 male and 9 female eligible patients were recruited for the Children's Oncology Group (COG) phase II study of Gemcitabine (ADVL0022). One of 20 evaluable patients with ALL and none of 10 evaluable patients with AML had complete responses to gemcitabine; there were no partial responses. Grade 3 or 4 hematologic toxicity and liver toxicity were common during therapy. Only one patient was alive 1 year after entry. The estimated 1-year overall survival probability for the 32 patients was 4% (SE = 3%). Gemcitabine at the dose and schedule in this trial was not effective for children with relapsed AML or ALL.
    Pediatric Blood & Cancer 03/2006; 46(2):193-7. · 2.35 Impact Factor
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    ABSTRACT: The prognosis for children with recurrent/refractory sarcomas is poor. We determined the overall response rate (ORR) and overall survival (OS) of children with recurrent/refractory sarcomas who were given ifosfamide, carboplatin, and etoposide (ICE) in three Children's Cancer Group (CCG) phase I/II trials. Children with recurrent/refractory sarcoma were treated with ifosfamide (1,800 mg/m2/day on day 0-4), carboplatin (400 mg/m2/day on day 0-1), etoposide (100 mg/m2/day on day 0-4) and either rhG-CSF (10 microg/kg/day vs. 5 microg/kg/day, CCG-0894, 71 patients), PIXY321 (500-1,000 microg/m2/day, CCG-0924, 14 patients), or rhG-CSF (5 microg/kg/day) and IL-6 (2.5-5 microg/kg/day, CCG-0931, 12 patients). Ninety-seven patients were evaluable for tumor response, 56 male and 41 female, median age 14.1 years (range 2.8-22.5 years). Tumor types were osteosarcoma (OTS) (n = 34), rhabdomyosarcoma (n = 27), Ewing sarcoma (EWS) (n = 21), soft tissue sarcoma-not otherwise specified (n = 5), undifferentiated sarcoma (n = 6), fibrosarcoma (n = 2), peripheral primitive neuroectodermal tumor (n = 1), and extraosseous Ewing (n = 1). The ORR was 51% (27% complete response [CR]). OS at 1 and 2 years was 49% and 28%, respectively. Patients with CR or partial response (PR) had significantly increased 1- and 2-year OS, 71% and 41%, respectively, (P < 0.001). Rhabdomyosarcoma patients with embryonal histology had significant improvement in 1- and 2-year OS: 82% and 46%, respectively, compared with other histologies, (P < 0.005). The ORR to ICE reinduction chemotherapy in children with recurrent/refractory sarcoma was 51%. OS of 1 and 2 years appeared significantly improved in patients who had CR or PR following ICE reinduction therapy or who had rhabdomyosarcoma with embryonal histology.
    Pediatric Blood & Cancer 05/2005; 44(4):338-47. · 2.35 Impact Factor
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    ABSTRACT: Ifosfamide, carboplatin, and etoposide (ICE) are associated with grade III/IV dose-limiting thrombocytopenia. The Children's Oncology Group conducted a phase I dose escalation, pharmacokinetic, and biological study of recombinant human thrombopoietin (rhTPO) after ICE in children with recurrent/refractory solid tumors (CCG-09717) to assess the toxicity and maximum tolerated dose of rhTPO administered at 1.2, 2.4, or 3.6 microg/kg per dose. Children received ifosfamide 1,800 mg/m2 on days 0 to 4, carboplatin 400 mg/m2 on days 0 to 1, and etoposide 100 mg/m2 on days 0 to 4. rhTPO was administered i.v. on days +4, +6, +8, +10, and +12 at 1.2, 2.4, or 3.6 microg/kg per dose. rhTPO was well tolerated and maximum tolerated dose was not reached. Median time to platelet recovery > or =100,000/microL of rhTPO at 1.2, 2.4, and 3.6 microg/kg/d was 24 days (22-24 d), 25 days (23-29 d), and 22 days (16-37 d), respectively. Patients required a median of 2 days of platelet transfusions (0-7 days). Mean (+/- SD) rhTPO maximum serum concentrations were 63.3 +/- 9.7 and 89.3 +/- 15.7 ng/mL and terminal half-lives were 47 +/- 13 and 64 +/- 42 hours after 2.4 and 3.6 microg/kg/d, respectively. There was a significant increase in colony-forming unit megakaryocyte upon WBC count recovery. rhTPO was well tolerated. Time to hematologic recovery and median number of platelet transfusions seem to be improved compared with historical controls receiving ICE + granulocyte colony-stimulating factor (CCG-0894).
    Clinical Cancer Research 04/2005; 11(7):2644-50. · 7.84 Impact Factor
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    ABSTRACT: Children Cancer Group (CCG) 1991 is the first childhood acute lymphoblastic leukemia trial within CCG that allowed the utilization of a staged approach to the consent process. One hundred and forty subjects participated in the Project on Informed Consent which compared the primary outcome measures in the consent process of patients enrolled in CCG-1991 with those enrolled in other CCG leukemia studies. The parents' trust scores were higher for the CCG-1991 compared with other protocols. Eighty percent of parents enrolled in CCG-1991 understood the distinction between the randomized clinical trial and the standard treatment arm, compared with 62.5% in the other studies, P = 0.05. Multiple other outcome measures suggested a positive impact from staged informed consent. Our results suggest that a consent process with a staged approach can help investigators obtain a more truly informed consent. Future research is needed to confirm the benefits of the staged approach to the informed consent process.
    Pediatric Blood & Cancer 06/2004; 42(5):433-7. · 2.35 Impact Factor
  • Anne Angiolillo, Naomi L C Luban
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    ABSTRACT: This article describes an 8-month-old boy with Langerhans cell histiocytosis and A-positive blood group who developed a febrile hemolytic transfusion reaction with hepatic and renal failure leading to his death secondary to hemolysis from an out-of-group platelet transfusion from an O-positive donor. High-titer anti-A antibody caused the hemolysis. Volume reduction of out-of-group platelets should be considered, particularly when single-donor platelet pheresis platelets are used in children with small plasma volumes.
    Journal of Pediatric Hematology/Oncology 05/2004; 26(4):267-9. · 0.97 Impact Factor
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    ABSTRACT: Most children diagnosed as having leukemia become research subjects in randomized clinical trials (RCTs), but little is known about how randomization is explained to or understood by parents. To investigate physicians' explanation and parental understanding of randomization in childhood leukemia RCTs. A multisite study of the informed consent communication process for RCTs of childhood leukemia. Consecutive cases were recruited from pediatric oncology inpatient wards at 6 US children's hospitals associated with major academic medical centers from July 1, 1999, until December 31, 2001. The informed consent conferences were observed and audiotaped, and the information obtained was coded and analyzed. Parents were interviewed shortly after the conference to ascertain their understanding. Parents and members of the health care team who participated in 137 informed consent conferences for children with newly diagnosed acute leukemia. Observed explanations of randomization and parental understanding of randomization after the consent conference. Randomization was explained by physicians in 83% of cases and a consent document was presented during the conference in 95% of cases. Interviews after the conference demonstrated that 68 (50%) of 137 parents did not understand randomization. Parents of racial minority and lower socioeconomic status were less likely to understand randomization (P<.001 for each). Discussion of specific clinical trial details and the presence of a nurse during the conference were associated with understanding. Eighty-four percent of children were enrolled in a leukemia trial. Despite oral and written explanation, half of the parents in this study did not understand randomization for childhood leukemia trials. To make informed consent more effective, future research must seek to improve communication during this critical interchange.
    JAMA The Journal of the American Medical Association 01/2004; 291(4):470-5. · 29.98 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2003; 1(5).

Publication Stats

283 Citations
85.86 Total Impact Points

Institutions

  • 2005–2014
    • George Washington University
      • Children's National Medical Center
      Washington, Washington, D.C., United States
    • Children's Hospital Los Angeles
      Los Angeles, California, United States
  • 2004–2010
    • Children's National Medical Center
      • Division of Oncology
      Washington, Washington, D.C., United States
  • 2007
    • The Children's Hospital of Philadelphia
      Philadelphia, Pennsylvania, United States