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1.
J Allergy Clin Immunol Pract ; 8(1): 273-282, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31377437

RESUMO

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients.

2.
Child Care Health Dev ; 45(4): 568-576, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30990913

RESUMO

BACKGROUND: Children with cancer live through intense emotional experiences that call for coping with stressful events. The narration of these events allows them to construct a detailed memory system, fostering the elaboration and attribution of meaning to the disease experience. In particular, shared memory between the parent and the child about past events (i.e., reminiscing) helps children to deal with negative emotional experiences, encouraging emotional regulation and adaptive coping strategies. The present study aims to investigate reminiscing in parent-child with cancer dyads, focusing on parents' reminiscing habits, parents' reminiscing style about acute and chronic events, and children's well-being, assessed with respect to emotional regulation and coping skills. METHOD: Fifteen children from ages 4 to 8 years admitted to a paediatric haematology and oncology ward of an Italian hospital, and their parents were engaged in a reminiscing conversation about acute and chronic events related to disease. Moreover, some questionnaires have been proposed to evaluate parents' reminiscing habits and children's emotional regulation and coping skills. Descriptive and quantitative analyses were conducted. RESULTS: The data showed that parents frequently practise reminiscing in everyday life, focusing on directive and socioemotional functions. In reminiscing conversations about acute and chronic events concerning their child's illness, they use an elaborative reminiscing style and an emotional reminiscing style mainly concerning chronic events. A positive correlation between this reminiscing style and children's adaptive coping strategies was found mainly in acute events. A negative correlation emerged between parents' emotional terms (emotional reminiscing) and children's difficulties in emotional regulation. CONCLUSION: This study underlines the benefits of elaborative and emotional reminiscing conversation, in order to help children with cancer and their families to cope with acute and chronic stressful events. Reminiscing can be a useful methodology for health professionals with a view to collecting information on patients' memories of illness.

3.
J Allergy Clin Immunol Pract ; 7(5): 1568-1577, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30716504

RESUMO

BACKGROUND: In the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, variable phenotypic expression may delay diagnosis. Panleukopenia, malignancy, and chronic lung disease all affect morbidity and mortality risks. Routinely used treatments include immunoglobulins, granulocyte-colony stimulating factor (G-CSF), and antibiotics; recent trials with a target C-X-C chemokine receptor type 4 (CXCR4) antagonist show promising results. OBJECTIVE: We sought to characterize the largest cohort of patients with WHIM and evaluate their diagnostic and therapeutic management. METHODS: Data were collected from an international cohort of 18 patients with CXCR4 mutations. RESULTS: The clinical features manifested at 2.2 ± 2.6 years of age, whereas the disease diagnosis was delayed until 12.5 ± 10.4 years of age. Patients with WHIM commonly presented with a severe bacterial infection (78%). Pneumonia recurrence was observed in 61% of patients and was complicated with bronchiectasis in 27%. Skin warts were observed in 61% of patients at a mean age of 11 years, whereas human papilloma virus (HPV)-related malignancies manifested in 16% of patients. All the patients had severe neutropenia (195 ± 102 cells/mm3 at onset), whereas lymphopenia and hypogammaglobulinemia were detected in 88% and 58% of patients, respectively. Approximately 50% of patients received antibiotic prophylaxis, whereas G-CSF and immunoglobulin treatments were used in 72% and 55% of patients, respectively. CONCLUSIONS: The WHIM syndrome onsets early in life and should be suspected in patients with chronic neutropenia. Patients with WHIM need careful monitoring and timely intervention for complications, mainly lung disease and HPV-related malignancies. We suggest that immunoglobulin therapy should be promptly considered to control the frequency of bacterial infections and prevent chronic lung damage.

4.
Eur J Nucl Med Mol Imaging ; 46(1): 97-106, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30219963

RESUMO

PURPOSE: We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin's lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial. METHODS: We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors. RESULTS: Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01). CONCLUSION: After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.


Assuntos
Doença de Hodgkin/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/normas , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Fluordesoxiglucose F18 , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Resultado do Tratamento
5.
J Neurooncol ; 140(2): 457-465, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30109673

RESUMO

PURPOSE: The aims of patients' radiological surveillance are to: ascertain relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if second-line therapy is not standardized/curative; and assess/treat iatrogenic effects. To lessen the emotional and socioeconomic burdens for patients and families, we ideally need to establish whether scheduled radiological surveillance gives patients a better outcome than waiting for symptoms and signs to appear. METHODS: We analyzed a prospective series of 160 newly-diagnosed and treated pediatric/adolescent patients with intracranial ependymoma, comparing patients with recurrent disease identified on scheduled MRI (the RECPT group; 34 cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group; 16 cases). The median follow-up was 67 months. RESULTS: No significant differences emerged between the two groups in terms of gender, age, tumor grade/site, shunting, residual disease, or type of relapse (local, distant, or concomitant). The time to relapse (median 19 months; range 5-104) and the MRI follow-up intervals did not differ between the SYMPPT and RECPT groups. The presence of signs/symptoms was an unfavorable factor for overall survival (OS) after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis, an adjusted model confirmed a significantly worse OS in the SYMPPT than in the RECPT patients. CONCLUSIONS: Symptomatic relapses carried a significantly worse survival for ependymoma patients than recurrences detected by MRI alone. It would therefore be desirable to identify recurrences before symptoms develop. Radiological follow-up should be retained in ependymoma patient surveillance because there is a chance of salvage treatment for relapses found on MRI.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Ependimoma/diagnóstico , Ependimoma/terapia , Adolescente , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Protocolos Clínicos , Ependimoma/mortalidade , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Prognóstico , Estudos Prospectivos
6.
Pediatr Blood Cancer ; 64(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28233470

RESUMO

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: Inclusion criteria for the study were as follows: a pathological diagnosis of "adult-type NRSTS," arising at visceral sites (lung-pleurae, liver, kidney, and mesentery-bowel); age under 18 years; no previous treatment except for primary surgery; available clinical data; and written consent. RESULTS: Thirty cases with visceral NRSTS were collected and analyzed. Sites of origin were as follows: mesentery-bowel in 12 cases, lung-pleurae in 11, liver in 5, and kidney in 2. According to the Intergroup Rhabdomyosarcoma Study (IRS) surgical grouping system, patients were classified as follows: nine IRS group I, three group II, 12 group III, and six group IV. Patients were treated with a multimodal approach including surgery, radiotherapy, and/or chemotherapy, according to their characteristics. For the series as a whole, the 5-year event-free and overall survival rates were 33.3% and 40.0%, respectively. The IRS group (reflecting the feasibility of initial complete resection) emerged as the main prognostic factor. Survival rates also correlated with tumor size and local invasiveness, histological subtype, and tumor sites (the worst outcome was seen for tumors arising in the lung and pleurae). CONCLUSIONS: This study confirmed that visceral NRSTS are aggressive tumors carrying a worse prognosis than pediatric NRSTS arising in soft tissues of the extremities. Local treatment remains the main challenge for these tumors.


Assuntos
Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Vísceras/patologia
7.
Neuro Oncol ; 18(10): 1451-60, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27194148

RESUMO

BACKGROUND: This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS: WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS: From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS: In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante/métodos , Ependimoma/terapia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Quimiorradioterapia Adjuvante/mortalidade , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Ependimoma/mortalidade , Ependimoma/patologia , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Procedimentos Neurocirúrgicos/mortalidade , Radioterapia , Resultado do Tratamento , Vincristina/administração & dosagem
8.
Am J Med Genet A ; 167A(8): 1902-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25846317

RESUMO

Noonan-like syndrome with loose anagen hair (NSLH), also known as Mazzanti syndrome, is a RASopathy characterized by craniofacial features resembling Noonan syndrome, cardiac defects, cognitive deficits and behavioral issues, reduced growth generally associated with GH deficit, darkly pigmented skin, and an unique combination of ectodermal anomalies. Virtually all cases of NSLH are caused by an invariant and functionally unique mutation in SHOC2 (c.4A>G, p.Ser2Gly). Here, we report on a child with molecularly confirmed NSLH who developed a neuroblastoma, first suspected at the age 3 months by abdominal ultrasound examination. Based on this finding, scanning of the SHOC2 coding sequence encompassing the c.4A>G change was performed on selected pediatric cohorts of malignancies documented to occur in RASopathies (i.e., neuroblastoma, brain tumors, rhabdomyosarcoma, acute lymphoblastic, and myeloid leukemia), but failed to identify a functionally relevant cancer-associated variant. While these results do not support a major role of somatic SHOC2 mutations in these pediatric cancers, this second instance of neuroblastoma in NSLAH suggests a possible predisposition to this malignancy in subjects heterozygous for the c.4A>G SHOC2 mutation.


Assuntos
Neuroblastoma/complicações , Síndrome de Noonan/fisiopatologia , Humanos , Recém-Nascido , Masculino , Síndrome de Noonan/complicações
9.
J Pediatr ; 164(2): 376-82.e1-2, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24252782

RESUMO

OBJECTIVE: To describe a series of cutaneous melanoma in children collected by the Italian Rare Tumors in Pediatric Age project. STUDY DESIGN: From 2000 to 2012, 54 patients younger than 18 years of age were prospectively registered and treated at 12 Italian pediatric centers on the basis of the same diagnostic/therapeutic recommendations and with the same forms to record clinical data. RESULTS: Considering the estimated annual incidence in Italy, the registered cases accounted for 30% of those expected in children and 10% of adolescents. Clinically, 47% of the tumors were amelanotic and 81% were raised, 39% of cases had tumor thickness >2 mm, and 36% had lymph node involvement. For the whole series, 5-year event-free survival and overall survival rates were 75.2% and 84.6%, respectively. Patient survival correlated with tumor stage and ulceration. No relapses were recorded for T1-2 (thickness <2 mm), N0, and stage 0-I-II cases. CONCLUSION: We suggest that the variables influencing survival in children with melanoma are the same as for adults, the clinical approach used in adults is feasible in children, and pediatric cases are more likely to have advanced disease at diagnosis but similar survival. New effective drugs are needed for advanced disease, and biological studies and international cooperative schemes are warranted.


Assuntos
Melanoma/epidemiologia , Estadiamento de Neoplasias , Adolescente , Distribuição por Idade , Biópsia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Melanoma/patologia , Estudos Retrospectivos , Distribuição por Sexo , Neoplasias Cutâneas , Taxa de Sobrevida/tendências
10.
J Neurooncol ; 113(3): 513-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23666235

RESUMO

The treatment of children with malignant glioma remains challenging. The aim of this multicenter phase I study is to establish the recommended dose (RD) of the combination therapy with temozolomide (TMZ) and oral etoposide (VP-16) in children with relapsed or refractory malignant glioma and brainstem glioma at diagnosis. A phase I trial was conducted to establish the maximum tolerated dose (MTD) of TMZ and oral VP-16. This orally administered combination was investigated by a classical 3 + 3 design. Cohorts of patients were enrolled at 4 different levels: (1) TMZ 120 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (2) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (3) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10; (4) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-12. Therapy was administered in 28-day courses. A total of 118 courses were administered to 18 patients with a median age of 11.2 years. At dose level 1, none displayed toxicity. Of the 6 patients at dose level 2, 1 patient had dose limiting toxicity (DLT). None of the 3 patients at dose level 3 had DLT. At dose level 4, grade III/IV thrombocytopenia and neutropenia were observed in 2 out of the 6 patients enrolled. Therefore, the MTD was established at dose level 3. The RD for phase II trial in children with malignant glial is TMZ 150 mg/m(2) for 5 days and VP-16 50 mg/m(2) for 10 days every 28 days.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Administração Oral , Adolescente , Neoplasias Encefálicas/secundário , Criança , Pré-Escolar , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Glioma/patologia , Humanos , Masculino , Dose Máxima Tolerável , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Temozolomida
11.
Eur J Immunol ; 41(10): 3075-84, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21792878

RESUMO

Autosomal-dominant hyper-IgE syndrome (AD-HIES) is a primary immunodeficiency caused by STAT3 mutations. This inherited condition is characterized by eczema, staphylococcal cold abscesses and recurrent pulmonary infections. Given that STAT3 is involved in IL-10 signaling, we examined the immunoregulatory role of IL-10 in inflammation by studying the effects of IL-10 on monocytes, neutrophils and monocyte-derived DCs from HIES subjects. Analysis of gene expression in PBMCs and neutrophils isolated from HIES patients and stimulated with LPS in the presence of IL-10 showed reduced expression of IL1RN, which encodes IL-1 receptor antagonist (IL-1ra), and SOCS3 mRNA but increased CXCL8 mRNA expression. Moreover, secretion of the anti-inflammatory protein IL-1ra was reduced in AD-HIES patients. DCs from HIES patients secreted higher levels of TNF-α, IL-6 and, to a lesser extent, IL-12 when these cells were cultured in the presence of IL-10. These results suggest that IL-10 activity is affected in myeloid cells (e.g. monocytes, DCs) of HIES patients. Impairment of IL-10 signaling in patients with AD-HIES might result in an altered balance between pro-inflammatory and anti-inflammatory signals and might lead to persistent inflammation and delayed healing after infections.


Assuntos
Interleucina-10/metabolismo , Síndrome de Job/genética , Síndrome de Job/imunologia , Fator de Transcrição STAT3/genética , Domínios de Homologia de src/genética , Adolescente , Adulto , Sequência de Bases , Células Cultivadas , Criança , Pré-Escolar , Células Dendríticas/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Proteína Antagonista do Receptor de Interleucina 1/biossíntese , Proteína Antagonista do Receptor de Interleucina 1/deficiência , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-10/imunologia , Interleucina-12/biossíntese , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Interleucina-8/genética , Lipopolissacarídeos/imunologia , Masculino , Monócitos/imunologia , Células Mieloides/imunologia , Células Mieloides/metabolismo , Neutrófilos/imunologia , Fosforilação , RNA Mensageiro/biossíntese , Fator de Transcrição STAT3/química , Fator de Transcrição STAT3/metabolismo , Análise de Sequência de DNA , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/biossíntese , Proteínas Supressoras da Sinalização de Citocina/deficiência , Proteínas Supressoras da Sinalização de Citocina/genética , Fator de Necrose Tumoral alfa/biossíntese
12.
Eur J Cancer ; 46(16): 2943-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20538454

RESUMO

BACKGROUND: The prognosis of recurrent or progressive medulloblastoma (MB) is still poor. This study was designed to investigate the potential therapeutic benefit of combination therapy with temozolomide (TMZ) and oral etoposide (VP-16) in children with progressive or relapsed MB. Given the oral administration of both drugs the regimen was administered outpatient. METHODS: A phase I trial was conducted to establish the maximum tolerated dose (MTD) of TMZ and oral VP-16. This orally administered combination was investigated by classical 3+3 design. Cohorts of patients were enrolled at four different levels: (1) TMZ 120 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (2) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (3) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10; (4) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-12. Therapy was administered in 28-d courses. A total of 66 courses were administered to 14 patients with a median age of 5.7 years. RESULTS: None of the 3 patients at dose levels 1 and 2 had dose-limiting toxicity (DLT). Of the 6 patients at dose level 3, 1 patient had DLT. At dose level 4, grade 4 thrombocytopaenia and neutropaenia were observed in the first 2 patients enrolled. Therefore, the MTD was established at dose level 3. CONCLUSION: The recommended phase II dose in children is TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10 every 28 d. The combination was well tolerated and demonstrated antitumour activity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Meduloblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Administração Oral , Adolescente , Criança , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Etoposídeo/administração & dosagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Dose Máxima Tolerável , Temozolomida , Resultado do Tratamento
13.
J Pediatr Adolesc Gynecol ; 22(4): e65-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19493520

RESUMO

BACKGROUND: Acute lymphoblastic leukemia is a malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace normal marrow hematopoietic cells, resulting in a marked decrease in the production of normal blood cells. CASE REPORT: We report a case of isolated ovarian relapse 7 years after the primary diagnosis in a patient, who was seemingly in clinical remission following unilateral ovariectomy and second-line chemotherapy. CONCLUSION: In contrast to testicular relapse, ovarian relapses in acute lymphoblastic leukemia are rarely reported. Surgical removal of the mass followed by chemotherapy is the therapeutic standard.


Assuntos
Neoplasias Ovarianas/secundário , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adolescente , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ovariectomia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/cirurgia
14.
Pathol Res Pract ; 204(12): 875-82, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18752906

RESUMO

Cylooxygenase-2 (Cox-2) inhibitors have increasingly become therapeutic alternatives in some Cox-2-overexpressing neoplasms. As the treatment eligibility for these drugs hinges on Cox-2 expression, Cox-2 immunostaining has recently been widely examined in several malignant neoplasms. However, data on the expression of Cox-2 in Wilms' tumor (WT) are limited. In this study, we examined Cox-2 expression in 40 examples of WT to identify the prognostic impact, to evaluate the effects on tumorigenesis, and to answer the question of whether neoplasms with Cox-2 expression could benefit from treatment with specific Cox-2 inhibitors. Sections from paraffin-embedded tumor samples were immunostained by a standard ABC technique using Cox-2 mouse monoclonal antibody. As in other rare examples reported in the literature, Cox-2 immunoreactivity was analyzed and correlated with histological features and the staging of neoplasms. However, in contrast to other studies, we also evaluated the relation of Cox-2 positivity to age, sex, and survival of patients. The results of this study demonstrated that Cox-2 was ubiquitously expressed in all cases of WT and their neovasculature, independently of the type of neoplasm (tumors with a favorable or unfavorable histology), tissues which constitute the neoplasm (blastemal, mesenchymal and epithelial, heterologous or non-heterologous elements), patient age, sex, or stage of development and survival rate. Thus, Cox-2 inhibitors could be used for treating all cases of WT. Further studies, including molecular investigations, would be useful to confirm our hypotheses.


Assuntos
Ciclo-Oxigenase 2/biossíntese , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Tumor de Wilms/enzimologia , Tumor de Wilms/patologia , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino
16.
Cancer ; 106(3): 703-7, 2006 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-16369989

RESUMO

BACKGROUND: Irinotecan (CPT-11) is a novel antineoplastic agent that takes effect by inhibiting topoisomerase I. The Italian Soft Tissue Sarcoma (STS) Committee performed a multiinstitutional Phase II study to evaluate its effect on STS. METHODS: Over a 2-year period between 2002 and 2004, 32 heavily pretreated patients were administered 60-minute infusions of irinotecan at 20 mg/m2/day, for 5 days a week, for 2 consecutive weeks. The courses were repeated every 4 weeks for at least 2 courses, unless there were signs of toxicity or disease progression. Thirty patients, 13 with peripheral primitive neuroectodermal tumor (PNET), 12 with rhabdomyosarcoma (RMS), 3 with desmoplastic small round cell tumor (DSRCT), and 2 with other STS were evaluable for response. RESULTS: A total of 79 cycles were delivered. The main regimen-related toxicity was diarrhea, occurring in 58% of cycles with 9 episodes graded as 3 or 4. Grade 3-4 neutropenia was recorded in 10% of cycles. The overall response rate was 23% (2 complete remissions +5 partial remissions of 30 patients), 38% for PNET and 16% for RMS. In addition, 4 minor responses were noted. CONCLUSIONS: As a single agent in the treatment of recurrent and refractory STS, irinotecan administered on a daily x5 x2 schedule revealed a noteworthy response rate in a population of heavily pretreated patients, especially in the subset of patients with PNET. Its hematologic toxicity profile warrants further investigation in association with other myelotoxic agents.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/análogos & derivados , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Criança , Pré-Escolar , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Lactente , Infusões Intravenosas , Irinotecano , Masculino , Neutropenia/induzido quimicamente , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Resultado do Tratamento
17.
J Pediatr Hematol Oncol ; 26(10): 649-655, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27811606

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the severity of hearing loss after cisplatin and/or carboplatin treatment in young children and to analyze its evolution and its relation to different therapy schedules. METHODS: One hundred twenty patients treated in the Pediatrics Department at the Institut Gustave-Roussy from 1987 to 1997 for neuroblastoma, osteosarcoma, hepatoblastoma, or germ cell tumors were analyzed. Median age at diagnosis was 2.6 (range 0-17) years. Median follow-up was 7 (1-13) years. Chemotherapy regimens contained cisplatin and/or carboplatin. Three patients also received high-dose carboplatin. Cisplatin was administered at a dose of 200 mg/m/course in 72% of cases. The median cumulative dose was 400 mg/m for cisplatin and 1,600 mg/m for carboplatin. Hearing loss of grade 2 or above, according to Brock's grading scale, was revealed with pure tone audiometry and behavioral techniques. RESULTS: Carboplatin alone was not ototoxic. Deterioration of hearing of grade 2 or above was observed in 37% of patients treated with cisplatin and 43% of patients treated with cisplatin plus carboplatin (P = NS). Fifteen percent of patients experienced grade 3 or 4 ototoxicity. Ototoxicity was most often observed after a total cisplatin dose of at least 400 mg/m. No improvement was observed with time; on the contrary, worsening or progression of hearing loss at lower frequencies was detected during follow-up. Only 5% of audiograms showed toxicity of at least grade 2 before the end of therapy; in contrast, this level was observed in 11% of early post-therapy evaluations and in 44% after more than 2 years of follow-up. CONCLUSIONS: Children treated with cisplatin at cumulative doses approaching 400 mg/m require long-term surveillance to avoid overlooking hearing deficits. Carboplatin, at a standard dose, does not appear to be a significant risk factor for ototoxicity even in patients who have already been treated with cisplatin.

18.
J Pediatr Hematol Oncol ; 26(10): 649-55, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15454836

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the severity of hearing loss after cisplatin and/or carboplatin treatment in young children and to analyze its evolution and its relation to different therapy schedules. METHODS: One hundred twenty patients treated in the Pediatrics Department at the Institut Gustave-Roussy from 1987 to 1997 for neuroblastoma, osteosarcoma, hepatoblastoma, or germ cell tumors were analyzed. Median age at diagnosis was 2.6 (range 0-17) years. Median follow-up was 7 (1-13) years. Chemotherapy regimens contained cisplatin and/or carboplatin. Three patients also received high-dose carboplatin. Cisplatin was administered at a dose of 200 mg/m/course in 72% of cases. The median cumulative dose was 400 mg/m for cisplatin and 1,600 mg/m for carboplatin. Hearing loss of grade 2 or above, according to Brock's grading scale, was revealed with pure tone audiometry and behavioral techniques. RESULTS: Carboplatin alone was not ototoxic. Deterioration of hearing of grade 2 or above was observed in 37% of patients treated with cisplatin and 43% of patients treated with cisplatin plus carboplatin (P = NS). Fifteen percent of patients experienced grade 3 or 4 ototoxicity. Ototoxicity was most often observed after a total cisplatin dose of at least 400 mg/m. No improvement was observed with time; on the contrary, worsening or progression of hearing loss at lower frequencies was detected during follow-up. Only 5% of audiograms showed toxicity of at least grade 2 before the end of therapy; in contrast, this level was observed in 11% of early post-therapy evaluations and in 44% after more than 2 years of follow-up. CONCLUSIONS: Children treated with cisplatin at cumulative doses approaching 400 mg/m require long-term surveillance to avoid overlooking hearing deficits. Carboplatin, at a standard dose, does not appear to be a significant risk factor for ototoxicity even in patients who have already been treated with cisplatin.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Perda Auditiva Neurossensorial/induzido quimicamente , Adolescente , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Audiometria , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Perda Auditiva Neurossensorial/epidemiologia , Humanos , Lactente , Masculino , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estresse Oxidativo , Estudos Retrospectivos
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