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1.
Genes Chromosomes Cancer ; 62(1): 39-46, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35716171

RESUMO

Ependymal tumors are the third most common brain tumor under 14 years old. Even though metastatic disease is a rare event, it affects mostly young children and carries an adverse prognosis. The factors associated with dissemination and the best treatment approach have not yet been established and there is limited published data on how to manage metastatic disease, especially in patients under 3 years of age. We provide a review of the literature on clinical characteristics and radiation-sparing treatments for metastatic ependymoma in children under 3 years of age treated. The majority (73%) of the identified cases were above 12 months old and had the PF as the primary site at diagnosis. Chemotherapy-based approaches, in different regimens, were used with radiation reserved for progression or relapse. The prognosis varied among the studies, with an average of 50%-58% overall survival. This study also describes the case of a 7-month-old boy with metastatic posterior fossa (PF) ependymoma, for whom we identified a novel SPECC1L-RAF1 gene fusion using a patient-centric comprehensive molecular profiling protocol. The patient was successfully treated with intensive induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic progenitor cell rescue (AuHSCR). Currently, the patient is in continuous remission 5 years after his diagnosis, without radiation therapy. The understanding of the available therapeutic approaches may assist physicians in their management of such patients. This report also opens the perspective of newly identified molecular alterations in metastatic ependymomas that might drive more chemo-sensitive tumors.


Assuntos
Neoplasias Encefálicas , Ependimoma , Transplante de Células-Tronco Hematopoéticas , Criança , Masculino , Humanos , Pré-Escolar , Lactente , Adolescente , Recidiva Local de Neoplasia , Ependimoma/tratamento farmacológico , Ependimoma/genética , Ependimoma/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico
2.
Pediatr Blood Cancer ; 70(11): e28493, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-32790146

RESUMO

Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.


Assuntos
Craniofaringioma , Hipopituitarismo , Neoplasias Hipofisárias , Criança , Humanos , Craniofaringioma/terapia , Renda , Gestão de Riscos , Neoplasias Hipofisárias/terapia
3.
J Neurooncol ; 157(1): 147-156, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35122583

RESUMO

INTRODUCTION: Ventriculo-peritoneal shunt (VPS) related ascites is a rare complication of pediatric low grade gliomas (pLGG). Physiopathology of this complication is not fully understood and there is paucity of data regarding the molecular profile of pLGG gliomas complicating with ascites and the optimal management of this unusual event. METHODS: International multi-institutional retrospective analysis of patients diagnosed with BRAF altered pLGG and ascites arising as a complication of VPS. Demographics, tumor characteristics, therapeutic approaches and outcomes were recorded. RESULTS: Nineteen patients were identified. Median age at diagnosis was 14 months (R: 2-144). Most patients (17; 89.4%) presented with lesions involving the optic pathway. Mean tumor standard volume was 34.8 cm2 (R: 12.5-85.4). Pilocytic Astrocytoma was the most frequent histological diagnosis (14;7 3.7%). Eight (42.1%) tumors harbored BRAF V600-E mutation and seven (36.8%) KIAA1549 fusion. The onset of ascites was documented at a median time of 5 months following VPS insertion. Four (21%) patients were managed with paracentesis only, 7(36.8%) required both paracentesis and shunt diversion, 7(36.8%) required only a shunt diversion and 1 (5.2%) patient was managed conservatively. Chemotherapy regimen was changed in 10 patients following ascites. Eight patients received targeted therapy (4 dabrafenib/4 trametinib) and 5 were radiated. There were eleven survivors with a median OS of 69 months (R: 3-144). CONCLUSIONS: Ascites is an early feature in the clinical course of young patients with midline BRAF altered pLGG, with high mortality rate observed in our cohort. The hypothesis of ascites as an adverse prognostic factor in pLGG warrants further prospective research.


Assuntos
Neoplasias Encefálicas , Glioma , Ascite/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Criança , Glioma/genética , Humanos , Estudos Retrospectivos , Derivação Ventriculoperitoneal/efeitos adversos
4.
Pediatr Blood Cancer ; 69(12): e30011, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36131594

RESUMO

BACKGROUND: Pediatric intracranial germ cell tumors (iGCT) are rare, with limited data available from Arabic countries. METHODS: We retrospectively reviewed the medical charts of children <18 years diagnosed with iGCT at King Hussein Cancer Center/Jordan (January 2003 to December 2020) for clinical characteristics, treatment, and morbidities. RESULTS: Sixteen patients had germinoma; median age was 6.9 years and median symptoms duration 8 months. Nine tumors were suprasellar, five pineal, and two bifocal. Four were metastatic. Eight patients had slightly elevated beta subunit human chorionic gonadotropin and 11 patients had resection/biopsy. Fifteen patients received chemotherapy; mostly carboplatin (450 mg/m2 )/etoposide, which had low toxicity. All patients received radiotherapy (different doses and fields). At median follow-up of 7.7 years, one tumor recurred (progression-free survival: 91% ± 8%). Twelve patients who continued follow-up had stable visual and endocrine deficits to their initial presentation. Five finished or are finishing diploma and seven had poor school performance (four left school). Six patients were diagnosed with nongerminomatous germ cell tumor; median symptom duration was 1 month. Three tumors were pineal, two suprasellar, and one at quadrigeminal plate. Three were metastatic. Five tested patients had high tumor markers and four had resection/biopsy. All patients received chemotherapy, and then five received craniospinal radiation. Two patients are alive, two died with tumor progression, one died in remission with electrolyte imbalance, and one developed leukemia and died with septic shock. CONCLUSIONS: We achieved excellent survival in treating germinoma using a feasible protocol for low middle-income countries. However, patients encountered significant morbidities exacerbated by delayed diagnosis and unnecessary surgical interventions despite abnormal tumor markers. Raising awareness on iGCT symptomatology and diagnosis may help limit these morbidities.


Assuntos
Neoplasias Encefálicas , Germinoma , Neoplasias Embrionárias de Células Germinativas , Criança , Masculino , Humanos , Jordânia/epidemiologia , Estudos Retrospectivos , Estudos de Viabilidade , Germinoma/patologia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Biomarcadores Tumorais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
5.
Pediatr Blood Cancer ; 68(8): e29054, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34022111

RESUMO

BACKGROUND: Treatment abandonment and refusal are reported to contribute significantly to poor survival of children with cancer in low- and middle-income countries. We aimed to assess this phenomenon among children diagnosed with central nervous system (CNS) tumors in Jordan. METHODS: We retrospectively reviewed the medical charts of children <18 years diagnosed with CNS tumors (2010-2020). Patients who abandoned or refused part of treatment were reviewed for their clinical characteristics, social circumstances, and possible reasons. We excluded patients referred for second opinion, radiotherapy only, or who traveled abroad for treatment. RESULTS: Four hundred seventy-three Jordanian children were identified; 12 families (2.5%) abandoned treatment, and 15 refused part of therapy (3%). Most patients were females (67%) and most had good or moderate performance status (89%). Most families (93%) lived within 2 hours from King Hussein Cancer Center. Most parents were university graduates (71%) and all fathers were employed, while 71% of mothers were housewives. The most common reasons to abandon or refuse therapy were treatment intensity in view of poor tumor outcome or bad quality of life, conflicting recommendations from other health care providers, "personal beliefs" against chemotherapy, and preference to use alternative medicine. CONCLUSIONS: Treatment abandonment and refusal in Jordanian children with CNS tumors is low. Universal cancer insurance, high level of education in the country, centralized cancer care in one institution, and the twinning program likely contributed to our low incidence. Improving knowledge on CNS tumors and better community rehabilitation and supportive services may help further decrease the abandonment and treatment refusal rate.


Assuntos
Neoplasias do Sistema Nervoso Central , Cooperação do Paciente , Recusa do Paciente ao Tratamento , Neoplasias do Sistema Nervoso Central/terapia , Criança , Feminino , Humanos , Jordânia/epidemiologia , Masculino , Cooperação do Paciente/estatística & dados numéricos , Qualidade de Vida , Estudos Retrospectivos , Recusa do Paciente ao Tratamento/estatística & dados numéricos
6.
Pediatr Blood Cancer ; 67(8): e28309, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32472748

RESUMO

Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low-resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Reparo de Erro de Pareamento de DNA , Genes Neoplásicos , Mutação em Linhagem Germinativa , Proteínas de Neoplasias/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/mortalidade , Humanos , Incidência
7.
Pediatr Blood Cancer ; 66(1): e27464, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30251335

RESUMO

BACKGROUND: Results of high-dose chemotherapy (HDCT) protocols for the management of malignant central nervous system (CNS) tumors in infants are mostly reported in high-income countries. We evaluated the feasibility and results of such protocols in a middle-income country (Jordan). METHODS: A retrospective study of infants' charts with CNS tumors between 2006 and 2015 who were treated according to HeadStart (HS) protocols. Data included patients' demographics, chemotherapy complications, and cost. RESULTS: We identified 18 patients with median age 29 months (range, 9-62 months) at diagnosis (12 HS-I and six HS-II). Distribution according to pathology was: atypical teratoid rhabdoid tumors (ATRT) (nine), primitive neuoroectodermal tumors (PNET)/pineoblastoma (five), and medulloblastoma (four). Six patients (33%) had metastatic disease, and 14 (78%) had an incomplete resection. Eleven patients achieved partial or complete remission, two stabilized, and five progressed. Ten patients did not proceed to HDCT due to progression (five), financial reasons (two), failure to collect stem cells (one), and undocumented reasons (two). Seventy-eight chemotherapy cycles were administered (median interval 26 days). Main complications during induction and consolidation were febrile neutropenia (73% and 100%), documented infections (8% and 13%), and mucositis (12% and 88%), respectively. Three patients developed moderate hearing loss. No protocol-related mortality was reported. At the last follow-up, five patients were alive: three with medulloblastoma (19, 29, and 89 months) and two with ATRT (18 and 42 months). Three survivors received focal/craniospinal radiation. The median cost of a complete HS protocol, excluding surgery/radiotherapy, was $103 500 per patient; 39% of the median cost was related to pharmacy expenses. CONCLUSIONS: These protocols were manageable in our context of limited health care resources. However, considering the significant costs and the modest survival rate, better selection criteria need to be used to identify patients likely to benefit from this approach.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/economia , Renda/estatística & dados numéricos , Quimioterapia de Indução/mortalidade , Pré-Escolar , Países em Desenvolvimento , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Childs Nerv Syst ; 35(6): 1035-1039, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30617578

RESUMO

PURPOSE: Medulloepithelioma is a rare brain tumor that has been classified as embryonal tumor with multilayered rosettes (ETMR) if it harbors C19MC amplification. In rare instances, it shows evidence of heterologous differentiation. METHODS: We report a case of a 10-year-old female who presented with headache, squint, and minimal left sided weakness of 1 week duration. RESULTS: Microscopy revealed a small round blue cell tumor with focal glandular and tubular differentiation. In one focus, well-developed osteoid was identified. The tumor labeled with LIN28A immunostain. CONCLUSIONS: Unusual features can be encountered in medulloepithelioma which should be in the differential diagnosis of CNS embryonal tumors. Full description of the case with review of the literature and comparison between cases with and without heterologous elements is presented.


Assuntos
Neoplasias Encefálicas/patologia , Tumores Neuroectodérmicos Primitivos/patologia , Ossificação Heterotópica/patologia , Criança , Feminino , Humanos
10.
J Pediatr Hematol Oncol ; 40(6): 478-482, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29200156

RESUMO

Pleomorphic xanthoastrocytoma is a rare brain tumor with unique high frequency of BRAF V600E mutation which is plausible for targeted therapy. The anaplastic variant has generally worse prognosis. We present an adolescent patient with a disseminated relapse of anaplastic pleomorphic xanthoastrocytoma following surgery, radiotherapy, and chemotherapy. She had a dramatic and prolonged response to a BRAF inhibitor (Dabrafinib) and later to addition of a MEK inhibitor (Trametinib) on tumor progression. With minimal side effects and a good quality of life, the patient is alive more than 2 years after initiation of targeted therapy. This experience confirms the potential role of targeted treatments in high-grade BRAF-mutated brain tumors.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Imidazóis/administração & dosagem , Mutação de Sentido Incorreto , Oximas/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Adolescente , Substituição de Aminoácidos , Astrocitoma/genética , Astrocitoma/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Feminino , Humanos
11.
Pediatr Blood Cancer ; 64 Suppl 52017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29297618

RESUMO

Effective treatment of children with low grade glioma (LGG) requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition, the treating centre should have the capacity to manage a variety of LGG and treatment-associated complications. These requirements have made it difficult for many centers in low and middle-income countries (LMIC) to offer effective treatment and follow up. This article provides management recommendations for children with LGG according to the level of facilities available.


Assuntos
Neoplasias Encefálicas/terapia , Países em Desenvolvimento , Glioma/terapia , Oncologia/métodos , Criança , Humanos , Oncologia/normas , Sociedades Médicas
12.
Childs Nerv Syst ; 33(6): 941-950, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28455541

RESUMO

BACKGROUND: Management of craniopharyngioma in children is challenging, and their quality of life can be significantly affected. Series describing this from low-middle income countries (LMIC) are few. PATIENTS AND METHODS: The study provides a retrospective chart review of pediatric patients <18 years old, diagnosed with craniopharyngioma between 2003 and 2014, and treated at King Hussein Cancer Center, Jordan. RESULTS: Twenty-four patients (12 males) were identified. Median age at diagnosis was 7.4 years (0.9-16.4 years). Commonest symptoms were visual impairment and headache (71%). Review of seventeen preoperative MRIs showed hypothalamic involvement in 88% and hydrocephalus in 76%. Thirteen patients (54%) had multiple surgical interventions. Five patients (21%) had initial gross total resection. Eleven patients (46%) received radiotherapy and six (25%) intra-cystic interferon. Five years' survival was 87 ± 7% with a median follow-up of 4.5 years (0.3-12.3 years). Four patients (17%) died; one after post-operative cerebral infarction and three secondary to hypothalamic damage. At their last evaluation, all but one patient required multiple hormonal supplements. Ten patients (42%) had best eye visual acuity (VA) >20/40, and four (16%) were legally blind. Eleven patients (46%) were overweight/obese; one had gastric bypass surgery. Seven patients had hyperlipidemia, and eight developed fatty liver infiltration. Eleven patients (65%) were attending schools and one at college. Nine of the living patients (53%) expressed difficulty to engage in the community. CONCLUSIONS: Management of pediatric craniopharyngioma is particularly complex and demanding in LMIC. Multidisciplinary care is integral to optimize the care and minimize the morbidities. A management outline for LMIC is proposed.


Assuntos
Craniofaringioma/economia , Craniofaringioma/terapia , Gerenciamento Clínico , Neoplasias Hipofisárias/economia , Neoplasias Hipofisárias/terapia , Pobreza/economia , Adolescente , Criança , Pré-Escolar , Craniofaringioma/diagnóstico , Feminino , Seguimentos , Humanos , Lactente , Masculino , Morbidade , Neoplasias Hipofisárias/diagnóstico , Pobreza/tendências , Estudos Retrospectivos , Fatores de Tempo
13.
Int J Cancer ; 138(2): 380-5, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26293621

RESUMO

Biallelic mismatch repair deficiency (bMMRD) is a cancer predisposition syndrome affecting primarily individuals from consanguinous families resulting in multiple childhood cancers including high grade gliomas (HGG). This is the first study to assess the prevalence of bMMRD among patients with HGG in countries where consanguinity is high. We collected molecular and clinical information on all children diagnosed with HGG and supratentorial primitive neuroectodermal tumors (sPNET) between 2003 and 2013 at King Hussein Cancer Center, Jordan. Comparison was made to a similar cohort from Toronto. Clinical data regarding presence of café au lait macules(CAL), family history of cancer, consanguinity, pathology and treatment were collected. Tumors were centrally reviewed and tested for MMRD by immunohistochemistry of the corresponding proteins. Forty-two patients fulfilled the inclusion criteria, including 36 with HGG. MMRD was observed in 39% of HGG of whom 79% also lost MMR staining in the corresponding normal cells suggestive of bMMRD. P53 dysfunction was highly enriched in MMR deficient tumors (p = 0.0003).The frequency of MMRD was significantly lower in Toronto cohort (23%, p = 0.03). Both evidence of CAL and consanguinity correlated with bMMRD (p = 0.005 and 0.05,respectively) but family history of cancer didn't. HGG with all three bMMRD risk factors had evidence of MMRD and all children affected by multiple bMMRD related cancers had identical gene loss by immunohistochemical staining. In Jordan, the frequency of clinical and immunohistochemical alterations suggestive of bMMRD in pediatric HGG is high. Genetic testing will enable appropriate counseling and cancer screening to improve survival of these patients.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Colorretais/epidemiologia , Reparo de Erro de Pareamento de DNA/genética , Glioma/genética , Síndromes Neoplásicas Hereditárias/epidemiologia , Adolescente , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Glioma/mortalidade , Glioma/patologia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Jordânia , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Estudos Retrospectivos , Fatores de Risco
14.
Neuropathology ; 36(1): 17-26, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26207291

RESUMO

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor of the CNS mostly seen in infants and is often associated with a dismal outcome. Despite the heterogeneous morphology and/or immunoprofile, its diagnosis nowadays relies on the negative INI-1/BAF47 nuclear immunostain in tumor cells. We aim to investigate a number of immunohistochemical antibodies as potential diagnostic and prognostic markers. All AT/RT cases in patients younger than 18 years of age were included. Demographics, clinical features and outcome were collected. Immunostains tested included SALL-4, OCT3/4, CD99, FLI-1, cyclin-D1, ß-catenin, P53, P16, CDX2 and WT-1. Nineteen cases (10 males) were identified at our center between 2004-2013 with a median age of 24 months. Ten (52.6%) cases were supratentorial. Six (42.9%) cases showed metastasis at time of presentation. Chemotherapy was administered to 10 (62.5%) and radiotherapy to seven (43.8%). The median overall survival was 11 months. A single long-term survival of 104 months was identified. Pathologically, most cases showed an admixture of rhabdoid cells and/or small cells and/or pale cells in variable proportions. Of all tested antibodies, only positivity for FLI-1 was associated with improved survival (P = 0.0012), while positivity for cyclin-D1 showed a trend toward improved survival (P = 0.0547). CDX2 was positive only in the single long-term survival. Interestingly, two cases showed co-expression of CD99 and FLI-1, and some were positive for SALL-4. In conclusion, FLI-1 and cyclin-D1 are potential prognostic markers associated with better outcome. Occasional AT/RT cases might co-express CD99 and FLI-1 as well as SALL-4, a potential diagnostic pitfall with Ewing sarcoma/ primitive neuroectodermal tumors and germ cell tumors, respectively.


Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Tumor Rabdoide/patologia , Teratoma/patologia , Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Neoplasias Infratentoriais/patologia , Neoplasias Infratentoriais/cirurgia , Masculino , Prognóstico , Tumor Rabdoide/cirurgia , Neoplasias Supratentoriais/patologia , Neoplasias Supratentoriais/cirurgia , Análise de Sobrevida , Teratoma/cirurgia , Resultado do Tratamento
15.
Childs Nerv Syst ; 32(3): 553-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26293676

RESUMO

Synchronous primary malignant brain tumors are rare. We present a 5-year-old boy with synchronous glioblastoma and medulloblastoma. Both tumor samples had positive p53 stain and loss of PMS2 and MLH1 stains. The child had multiple café au lait spots and a significant family history of cancer. After subtotal resection of both tumors, he received craniospinal radiation with concomitant temozolomide followed by chemotherapy, alternating cycles of cisplatin/lomustine/vincristine with temozolomide. Then, he started maintenance treatment with cis-retinoic acid (100 mg/m(2)/day for 21 days). He remained asymptomatic for 34 months despite a follow-up brain MRI consistent with glioblastoma relapse 9 months before his death. Cis-retinoic acid may have contributed to prolong survival in this child with a probable biallelic mismatch repair syndrome.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Colorretais/complicações , Glioblastoma/genética , Meduloblastoma/genética , Neoplasias Primárias Múltiplas/genética , Síndromes Neoplásicas Hereditárias/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapia , Pré-Escolar , Neoplasias Colorretais/genética , Terapia Combinada , Irradiação Craniana , Evolução Fatal , Mutação em Linhagem Germinativa , Glioblastoma/terapia , Humanos , Masculino , Meduloblastoma/terapia , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Neoplasias Primárias Múltiplas/terapia , Síndromes Neoplásicas Hereditárias/genética , Proteína Supressora de Tumor p53/genética
16.
J Oncol Pharm Pract ; 21(5): 384-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24781453

RESUMO

PURPOSE: To describe a medication error of intrathecal Cytarabine overdose that was managed conservatively with no apparent toxicities. SUMMARY: An 11-year-old girl was diagnosed with bone marrow relapsed precursor B-cell acute lymphoblastic leukemia. According to her chemotherapy protocol, she was started on triple intrathecal chemotherapy consisting of Methotrexate, Cytarabine and Hydrocortisone on day 1 of the protocol. After the intrathecal therapy being administered to the patient, the pharmacist who checked the medication realized that the wrong formulation of Cytarabine was used to prepare the intrathecal therapy; this error resulted in five times overdose of Cytarabine. The patient was then managed conservatively without cerebrospinal fluid exchange. Our patient remained clinically and neurologically stable without apparent toxicities and was discharged safely from hospital. CONCLUSION: Supportive care without the need for invasive procedures such as cerebrospinal fluid exchange may be adequate for managing intrathecal Cytarabine overdose.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/efeitos adversos , Overdose de Drogas , Erros de Medicação , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Citarabina/administração & dosagem , Feminino , Humanos , Injeções Espinhais , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico
17.
Front Oncol ; 14: 1329024, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440233

RESUMO

Introduction: Advances in molecular diagnostics led to improved targeted interventions in the treatment of pediatric CNS tumors. However, the capacity to test for these is limited in LMICs, and thus their value needs exploration. Methods: We reviewed our experience with NGS testing (TruSight RNA Pan-Cancer-seq panel) for pediatric CNS tumors at KHCC/Jordan (March/2022-April/2023). Paraffin blocks' scrolls were shipped to the SickKids laboratory based on the multidisciplinary clinic (MDC) recommendations. We reviewed the patients' characteristics, the tumor types, and the NGS results' impact on treatment. Results: Of 237 patients discussed during the MDC meetings, 32 patients (14%) were included. They were 16 boys and 16 girls; the median age at time of testing was 9.5 years (range, 0.9-21.9 years). There were 21 samples sent at diagnosis and 11 upon tumor progression. The main diagnoses were low-grade-glioma (15), high-grade-glioma (10), and other histologies (7). Reasons to request NGS included searching for a targetable alteration (20) and to better characterize the tumor behavior (12). The median turnaround time from samples' shipment to receiving the results was 23.5 days (range, 15-49 days) with a median laboratory processing time of 16 days (range, 8-39 days) at a cost of US$1,000/sample. There were 19 (59%) tumors that had targetable alterations (FGFR/MAPK pathway inhibitors (14), checkpoint inhibitors (2), NTRK inhibitors (2), and one with PI3K inhibitor or IDH1 inhibitor). Two rare BRAF mutations were identified (BRAFp.G469A, BRAFp.K601E). One tumor diagnosed initially as undifferentiated round cell sarcoma harbored NAB2::STAT6 fusion and was reclassified as an aggressive metastatic solitary fibrous tumor. Another tumor initially diagnosed as grade 2 astroblastoma grade 2 was reclassified as low-grade-glioma in the absence of MN1 alteration. NGS failed to help characterize a tumor that was diagnosed histologically as small round blue cell tumor. Nine patients received targeted therapy; dabrafenib/trametinib (6), pembrolizumab (2), and entrectinib (1), mostly upon tumor progression (7). Conclusion: In this highly selective cohort, a high percentage of targetable mutations was identified facilitating targeted therapies. Outsourcing of NGS testing was feasible; however, criteria for case selection are needed. In addition, local capacity-building in conducting the test, interpretation of the results, and access to "new drugs" continue to be a challenge in LMICs.

18.
Pediatr Transplant ; 17(4): 394-402, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23692601

RESUMO

HSCT can be curative for many PID. Little is known about the outcome of HSCT for patients with PID in the developing countries. We retrospectively reviewed all children with PID who received HSCT at KHCC in Jordan between August 2003 and October 2011. Twenty-eight patients were identified. The median age was 16 months (3 months-17 yr). Patients' diagnoses were SCID (n = 16), CHS (n = 3), HLH (n = 3), WAS (n = 2), Griscelli syndrome (n = 1), ALPS (n = 1), Omenn's syndrome (n = 1), and DiGeorge syndrome (n = 1). Seventeen patients received HLA-matched related HSCT, eight received maternal un-manipulated haploidentical HSCT, and three received unrelated cord blood transplantation. Nine patients (32%) developed BCGosis secondary to reactivation of pretransplant vaccination. Three died while still receiving anti-tuberculosis drugs, one still on treatment, and all others have recovered. Six patients had graft failure; four of them received no conditioning regimens. At a median follow up of 32 months (range 1-67), 21 patients are alive, with overall survival of 72%. We conclude that HSCT for PID patients can be performed with a good outcome in developing countries; however, delayed diagnosis or referral and BCG reactivation are unique challenges.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes de Imunodeficiência/terapia , Adolescente , Síndrome de Chediak-Higashi/terapia , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Síndrome de DiGeorge/terapia , Feminino , Perda Auditiva Neurossensorial/terapia , Humanos , Lactente , Jordânia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Piebaldismo/terapia , Transtornos da Pigmentação/terapia , Estudos Retrospectivos , Imunodeficiência Combinada Severa/terapia , Resultado do Tratamento , Síndrome de Wiskott-Aldrich/terapia
19.
Clin Ophthalmol ; 16: 2933-2942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071723

RESUMO

Purpose: This study aims to report visual acuity outcomes for patients with optic pathway gliomas (OPG) treated with systemic chemotherapy and analyze the associated factors. Patients and Methods: A retrospective study of 29 children with OPG treated with chemotherapy at King Hussein Cancer Center (KHCC), Amman, Jordan, between May/2005 and August/2020. Details on patient demographics, tumor location, systemic chemotherapy, and progression of disease were extracted from medical records. Results: Fifty-four eyes of twenty-nine patients were included in this study with a follow-up range from 2 to 17 years. Sixteen patients (55%) had a history of neurofibromatosis-1 (NF1). Most of the eyes (31, 57%) had visual acuity ranges in the moderate or better group. The age group ≥5 years at diagnosis, those with hydrocephalus, and patients with non-NF1 presented the worst visual acuity ranges from severe or worse; the p-value was 0.043, 0.0320, and 0.0054, respectively. Following treatment with systemic chemotherapy, visual acuity improved in 5 (17%) patients, remained the same in 23 (79%) patients, and only one patient (3%) had vision deterioration. Of the five patients who showed vision improvement, only one had radiological regression of the tumor. Parallel to this, three (10%) patients showed tumor progression in the final magnetic resonance image (MRI) findings without affecting the final vision. Conclusion: Children older than 5 years at diagnosis, in sporadic OPG, and those with hydrocephalus had the worst vision at presentation. Treatment with systemic chemotherapy prevented further deterioration of vision, and following treatment with systemic chemotherapy, most of the patients had the same vision; this stability indicates that vision at diagnosis is an important predictor for the final visual outcome.

20.
Pediatr Blood Cancer ; 56(1): 86-9, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21108443

RESUMO

BACKGROUND: Limited data are available on disease characteristics and outcome of children with cancer who contracted the H1N1 influenza infection during the 2009 pandemic. METHODS: All 76 pediatric patients with cancer and documented H1N1 infection who presented to the Pediatric Department at King Hussein Cancer Center (KHCC) between October 1 and December 1, 2009 were reviewed for clinical characteristics and course of the disease. RESULTS: Two-thirds of the patients had hematological malignancies and half were receiving non-intensive chemotherapy at the time of infection. With the exception of two patients who needed pediatric intensive care unit admission, the course of the remaining patients was uneventful whether they were hospitalized or not. No deaths related to H1N1 influenza infection were reported. Sixty-three percent of patients became afebrile within 48 hr of receiving oseltamivir. One-third of hospitalized patients were discharged in < 3 days. CONCLUSION: The course of H1N1 influenza infection in children with cancer appears to be mild in most cases.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/tratamento farmacológico , Neoplasias/complicações , Adolescente , Criança , Pré-Escolar , Febre/tratamento farmacológico , Febre/etiologia , Neoplasias Hematológicas/complicações , Humanos , Oseltamivir/uso terapêutico , Pandemias , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
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