Abstract:
BACKGROUND:Progressive/recurrent high-grade and diffuse intrinsic pontine gliomas (DIPGs) are fatal. Treatments targeting molecular pathways critical for these cancers are needed. METHODS:We conducted a phase 1 study (rolling-six design) to establish the safety and maximum tolerated dose (MTD) of dasatinib, an oral platelet-derived growth factor receptor A (PDGFRA) inhibitor, and crizotinib, an oral c-Met inhibitor, in such patients. Pharmacokinetics of both agents were performed. Biomarkers of cellular pathway activation in peripheral-blood mononuclear cells (PBMC) were evaluated before and after administration of dasatinib. PDGFRA and MET amplification, and PDGFRA mutations were studied in tumor samples. RESULTS:Twenty-five patients were enrolled in this study (median age: 11.9 years). Eleven patients had DIPG. Glioblastoma accounted for 40% of cases. Dasatinib at 50 mg/m2 and crizotinib at 130 mg/m2 or 100 mg/m2 were poorly tolerated when administered twice daily. Drug administration was then switched to once daily. Dasatinib administered at 50 mg/m2 and crizotinib at 215 mg/m2 once daily was the MTD. Dose-limiting toxicities consisted of diarrhea, fatigue, proteinuria, hyponatremia, rash, and grade 4 neutropenia. Only two patients received therapy for at least 6 months. No objective radiologic responses were observed. Pharmacokinetics of dasatinib and crizotinib were comparable to previous studies. A statistically significant decrease in the ratio of p-AKT/total AKT in PBMC occurred after dasatinib administration. PDGFRA and MET amplification were found in four and two cases, respectively. Only one of 10 tumors harbored a PDGFRA mutation. CONCLUSIONS:This drug combination was poorly tolerated and its activity was minimal. We do not recommend further testing of this combination in children.
journal_name
Pediatr Blood Cancerjournal_title
Pediatric blood & cancerauthors
Broniscer A,Jia S,Mandrell B,Hamideh D,Huang J,Onar-Thomas A,Gajjar A,Raimondi SC,Tatevossian RG,Stewart CFdoi
10.1002/pbc.27035subject
Has Abstractpub_date
2018-07-01 00:00:00pages
e27035issue
7eissn
1545-5009issn
1545-5017journal_volume
65pub_type
杂志文章abstract:BACKGROUND:Deaths during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL) account for one-tenth of ALL-associated mortality and half of ALL treatment-related mortality. We sought to ascertain patient- and hospital-level factors associated with induction mortality. PROCEDURE:We performed a retros...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24855
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Nephrogenic rests (NRs) are abnormally persistent foci of embryonal cells, thought to be the precursor lesion of Wilms tumors (WTs). To date, their presence has not been systematically examined in WTs treated with preoperative chemotherapy. METHODS:A systematic analysis of the data on NRs in WTs treated wit...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/pbc.26547
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:The views and clinical practice of children's cancer units were surveyed regarding management of central venous catheter (CVC) occlusion (CVC-occlusion), CVC-related thrombosis (CVC-thrombosis) and thromboembolism (CVC-thromboembolism). PROCEDURE:A questionnaire was sent to all 22 United Kingdom Children's ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/pbc.21332
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND:Previous studies of children with homozygous sickle cell anemia (SCA) show impaired growth and maturation. The correlation of this suboptimal growth with metabolic and hematological factors during puberty is poorly understood. PROCEDURE:We studied a group of pre-adolescent children with SCA (19 males, 14 fe...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22137
更新日期:2009-10-01 00:00:00
abstract::There is mounting evidence that combination of antibiotic therapy with vancomycin and piperacillin/tazobactam (pip/tazo) is associated with acute kidney injury (AKI). To determine whether vancomycin plus pip/tazo is associated with higher rates of AKI compared to vancomycin plus cefepime among pediatric hematology/onc...
journal_title:Pediatric blood & cancer
pub_type: 临床试验,杂志文章
doi:10.1002/pbc.27750
更新日期:2019-07-01 00:00:00
abstract::A 6-year-old female was admitted with abdominal pain and a mass in the right abdomen. Her lactose dehydrogenase level was 1,200 IU/L, and neuron specific enolase was 120 ng/ml. Computed tomography scan confirmed a large right renal mass with necrosis. A right radical nephrectomy was performed. The tumor was completely...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20831
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) has historically been of prognostic and therapeutic importance. However, classification has been complicated by shifting histologic criteria required for an ARMS diagnosis. Children's Oncology Group (COG) studies after IRS...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26645
更新日期:2017-12-01 00:00:00
abstract::Immune-mediated hemolytic anemia is a well-recognized complication of hematopoietic stem cell transplantation. We report on a 6-year-old boy with X-linked adrenoleukodystrophy who developed severe delayed alloimmune hemolytic anemia associated with immune-mediated neutropenia and thrombocytopenia following major ABO i...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.21187
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND:Primary epithelial lung malignancies are rare in childhood and adolescence. We reviewed the Memorial Sloan-Kettering Cancer Center experience with these tumors to better understand their histology, time to diagnosis, treatment, and outcome. PROCEDURE:A retrospective review was performed on all patients 21 y...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20279
更新日期:2005-10-15 00:00:00
abstract:BACKGROUND:Better predictors of outcome would allow improved risk-adapted therapy for pediatric nonmetastatic osteosarcoma of the extremity. We investigated the predictive value of MR imaging-based measures of absolute and relative tumor size and volume at the time of diagnosis. We also assessed the relation of tumor s...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20077
更新日期:2004-12-01 00:00:00
abstract:INTRODUCTION:Understanding factors that affect the decisions of caregivers of African children to enroll their children in clinical trials would lead to more fully informed consent. METHODS:During the NOHARM study (NCT01976416), a placebo-controlled clinical trial of hydroxyurea for Ugandan children with sickle cell a...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.27830
更新日期:2020-02-01 00:00:00
abstract::Children suffering from Acute Lymphoblastic Leukaemia (ALL) treated with asparaginase and corticosteroids are at risk of developing severe lipid abnormalities. The authors report the case of a 10-year-old male with extremely high plasma triglyceride concentrations (4,000 mg/dl) during the induction phase of ALL associ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20986
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Pediatric nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) may rarely occur in visceral tissues, and little is known about their clinical history. The present study retrospectively analyzed a group of patients prospectively registered in Italian pediatric protocols conducted between 1979 and 2004. METHODS:I...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26490
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Symptoms of epidural compression (SEC) in children with neuroblastoma (particularly infants) may be misinterpreted, leading to delay in diagnosis. PATIENTS AND METHODS:Clinical, imaging and follow-up data of 34 infants with neuroblastoma and SEC diagnosed between 2000 and 2011 at Italian AIEOP centers were ...
journal_title:Pediatric blood & cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/pbc.25028
更新日期:2014-08-01 00:00:00
abstract::The youngest siblings may be both emotionally vulnerable and often neglected members of the family of a childhood cancer patient. The prompt identification of signs of distress in these subjects allows trained caregivers to intervene with personalized, age-appropriate, attention, and care. A narrative approach, based ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.21056
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Central nervous system (CNS) malignancies are the most common solid tumors among children, and novel therapies are needed to help improve survival. Pomalidomide is an immunomodulatory agent that displays antiangiogenic and cytotoxic activity, making it an appropriate candidate to explore in pediatric CNS tum...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28756
更新日期:2021-02-01 00:00:00
abstract:BACKGROUND:Advanced irradiation techniques, including intensity-modulated radiation therapy (IMRT), aim to limit irradiation to adjoining tissues by conforming beams to a well-defined volume. In intracranial germinomas, whole-ventricular IMRT decreases the volume of irradiation to surrounding parenchyma. This study exa...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28005
更新日期:2019-12-01 00:00:00
abstract::X-linked lymphoproliferative syndrome (XLP) is caused by mutations in SH2D1A, and is associated with overwhelming infectious mononucleosis, aplastic anemia, hypogammaglobulinemia, and B-cell lymphomas. However, the frequency of SH2D1A mutations in males who present with B NHL is unknown. Five cases of XLP were diagnos...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.24525
更新日期:2013-09-01 00:00:00
abstract::Osteosarcoma is the most common bone tumor in children and young adults, with few advances in survival and treatment, especially for metastatic disease, in the last 30 years. Recently, immunotherapy has begun to show promise in various adult cancers, but the utility of this approach for osteosarcoma remains relatively...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,评审
doi:10.1002/pbc.27227
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:Morphological evaluation of early response to chemotherapy and measurement of minimal residual disease by flow cytometry or PCR are being used for evaluation of prognosis and treatment stratification in children with acute lymphoblastic leukaemia (ALL). PROCEDURE:In a series of 14 consecutive bone marrow in...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23081
更新日期:2011-08-01 00:00:00
abstract::Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare autosomal recessive disorder characterized by thrombocytopenia from failure of megakaryopoiesis. CAMT is one of the bone marrow failure syndromes, and the disease progression may involve other lineages leading to pancytopenia. The genetic background of CAMT ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22842
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Since there is no validated assay to monitor disease in children with neuroblastoma (NB), we tested whether NB specific cell-free RNA could be detected in their plasma samples. Moreover, with the aim of reducing patients' discomfort, we compared this assay to a recently standardized procedure that uses a lar...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.22498
更新日期:2010-07-01 00:00:00
abstract::Pseudomyogenic hemangioendothelioma (PMH) is a rare, mostly indolent vascular tumor. Extensive cases are treated with amputation as chemotherapy seems to be ineffective. Recently, promising results were published using mammalian target of rapamycin (mTOR) inhibitors in tumors of vascular origin. Here, we present a cas...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26781
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:Patients with sickle cell anemia (SCA) experience a broad range of psychiatric disorders, placing them at risk for more complicated and longer hospitalizations for vaso-occlusive crises (VOC). The current study examined the frequency of psychiatric disorders in SCA patients (ages birth to 20 years) admitted ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23117
更新日期:2012-02-01 00:00:00
abstract::Acute gastrointestinal graft-versus-host disease (GVHD) refractory to first-line treatment with systemic corticosteroids results in increased morbidity and potential mortality. We retrospectively assessed the feasibility and efficacy of catheter-directed intra-arterial platelet infusion (IAPI) in two pediatric patient...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章,评审
doi:10.1002/pbc.25633
更新日期:2015-12-01 00:00:00
abstract::Primary choriocarcinoma of the liver is an extremely rare childhood malignancy frequently associated with clinical instability at initial presentation. It often mimics other benign and malignant childhood liver tumors. Prompt diagnosis and initiation of treatment are necessary to attain a successful outcome. We descri...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.20623
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Wilms tumor is the most common pediatric renal malignancy, but the parameters that are important to its invasion capacity are poorly understood. The aim of this study was to identify new proteins associated with the invasion capacity of Wilms tumor. PROCEDURE:Gene expression profiles for 15 primary Wilms tu...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23003
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy. PROCEDURES:Retrospectively, we estimated the effect of CNS involvement and...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.26191
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND:The objective was to investigate factors associated with patient-related timing (PRT) to seek healthcare and health service-related timing (HSRT) to diagnose cancer and provide treatment to children without social security in Mexico. PROCEDURE:A cross-sectional survey was conducted in 13 Ministry of Health ...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.28331
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Pegasparaginase (PEG) is important for treatment of Acute Lymphoblastic Leukemia (ALL). Despite conjugation to polyethylene glycol to reduce immunogenicity, allergic reactions still occur and may be severe. Traditionally, PEG is given via intramuscular (IM) injection but recent protocols have shown it can be...
journal_title:Pediatric blood & cancer
pub_type: 杂志文章
doi:10.1002/pbc.23380
更新日期:2012-09-01 00:00:00