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Mutación de Línea Germinal , Síndrome de Li-Fraumeni , Neoplasias Peritoneales , Proteína p53 Supresora de Tumor , Humanos , Síndrome de Li-Fraumeni/genética , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Proteína p53 Supresora de Tumor/genética , Mesotelioma/genética , Mesotelioma/patología , Femenino , Masculino , NiñoRESUMEN
OBJECTIVES: In the etiology of childhood cancers, many genetic and environmental factors play a role. One of these factors could be cigarette smoking, and the main source of tobacco smoke exposure of children is parental smoking. However, establishing a causal relationship between parental smoking and childhood cancers has proven challenging due to difficulties in accurately detecting tobacco smoke exposure METHODS: To address this issue, we used hair cotinine analysis and a questionnaire to get information about tobacco smoke exposures of pediatric cancer patients and healthy children. A total of 104 pediatric cancer patients and 99 healthy children participated in our study. Parental smoking behaviors (pre-conceptional, during pregnancy, and current smoking) and environmental tobacco smoke (ETS) exposures of children are compared. RESULTS: We have found no differences between two groups by means of maternal smoking behaviors. However, the rates of paternal pre-conceptional smoking and smoking during pregnancy were significantly low in cancer patients (p < .05). These data suggest that social desirability bias among fathers of cancer patients may have contributed to this discrepancy. According to questionnaire, cancer patients had significantly lower ETS exposures than healthy children (p < .05). However, ETS exposure assessment through cotinine analysis demonstrated that cancer patients had higher exposure to ETS compared to healthy children (p < .001). CONCLUSION: Our findings provide evidence supporting the potential role of smoking as a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.
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Cotinina , Cabello , Neoplasias , Contaminación por Humo de Tabaco , Humanos , Femenino , Contaminación por Humo de Tabaco/efectos adversos , Contaminación por Humo de Tabaco/análisis , Masculino , Cotinina/análisis , Niño , Encuestas y Cuestionarios , Neoplasias/etiología , Neoplasias/epidemiología , Cabello/química , Preescolar , Padres , Embarazo , Adulto , Estudios de Casos y Controles , Adolescente , Fumar/efectos adversos , Estudios de SeguimientoRESUMEN
BACKGROUND: Oxidative stress has a potential role in carcinogenesis. Anti-oxidant enzymes have a neutralizing effect on both cancer initiation and progression. We aimed to assess the oxidant and anti-oxidant levels of pediatric cancer patients and to compare the levels in healthy controls. MATERIALS AND METHODS: The study involved 105 pediatric cancer patients (40 undergoing chemotherapy, 65 survivors) and 40 healthy children. The serum total oxidant status (TOS) and total anti-oxidant status (TAS) were measured. RESULTS: The oxidative stress index was significantly lower in pediatric cancer patients compared to the levels in the controls (0.20 ± 0.07 vs. 0.26 ± 0.10; P = 0.001). The mean serum TAS level was significantly higher in patient groups compared to the level in the control (1.87 ± 0.48 vs. 1.63 ± 0.32 mmol/L, P = 0.001). The TAS level of children with cancer in survivors was also found to be significantly higher compared to the levels in the control group (1.85 ± 0.45 vs. 1.63 ± 0.32 mmol/L, P = 0.005). Radiotherapy, surgery, relapsed disease, presence of metastases, and receiving enteral nutritional support caused no change in the TAS/TOS level. CONCLUSION: It has been revealed for the first time that the serum total anti-oxidant level was high in children undergoing chemotherapy and the survivor group as well. Moreover, the oxidative stress index was low in children with cancer. Longitudinal prospective studies are needed to reveal the alterations in oxidant status among children with cancer.
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Antioxidantes , Neoplasias , Niño , Humanos , Antioxidantes/metabolismo , Oxidantes , Estrés Oxidativo , Neoplasias/terapia , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Long-term survivors of Hodgkin lymphoma (HL) are at risk of developing a range of late effects, with a second malignant neoplasm and cardiovascular diseases being the leading causes of death in these patients. The present study aims to evaluate the late side effects in children with HL. MATERIALS AND METHODS: Out of 53 HL patients, we assessed the long-term effects of childhood HL survivors (HLSs; n = 50) diagnosed between 1998 and 2019. Patient data related to chronic health conditions, and sociodemographic characteristics were compared with their siblings (n = 56). RESULTS: The cumulative overall survival (OS) at 1, 5, and 10 years from diagnosis was 98.1 ± 1.9%, 93.3 ± 3.8%, and 93.3 ± 3.8%, respectively. Groups of HLSs and their siblings were matched according to age and gender. Compared with siblings, survivors had will be changed as 'a higher frequency of nephrotoxicity (P = 0.02)', cardiotoxicity (P = 0.12), thyroid dysfunction (P = 0.001), health care service usage (P < 0.01), limitation of physical function (P = 0.01), and pulmonary disease (P = 0.01). The control group of siblings had a higher incidence of marital status (P < 0.01), parenthood (P = 0.01), and smoking habit (P = 0.03). Thyroid dysfunction was associated with neck radiotherapy (P < 0.01). No secondaryneoplasm was detected. In relapsed, refractory setting (n = 10), autologous transplantation (n = 9) is performed after a complete remission. Brentuximab vedotin with or without bendamustine and rituximab is also used in selected patients. CONCLUSIONS: Increased number of chronic health conditions and social problems point to the significance of long-term follow-up of HLSs. We are currently preparing a survivorship guideline appropriate for Turkey's conditions. IMPLICATIONS FOR CANCER SURVIVORS: Renal, heart, pulmonary impairment, thyroid dysfunction, limitation in physical functioning, and deterioration in social status (marriage, having children, education).
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Hereditary forms of Medullary thyroid carcinoma (MTC) are rare. Different phenotypes with the same mutation may be due to differences in the timing of RET activation steps, additional mutations in other regions of the gene, or the co-occurrence of germline and somatic mutations, which is an infrequent possibility. Here, we aim to present the different features and difficulties in the follow-up of three family members with the same germline mutation. A 4-year-old male patient with respiratory distress was diagnosed with MTC and found to have a heterozygous germline mutation C.2671T>G(S891A) in the RET gene (classified as intermediate risk according to ATA). As the tumor was inoperable, treatment with a tyrosine kinase inhibitor (sorafenib) was initiated. Sorafenib has prevented tumor progression for seven years. Whole exome sequencing (WES) did not identify additional mutations. Segregation analysis showed the same mutation in the asymptomatic mother and sister. In our case, thyroid tissues were examined for somatic mutations, and SDHA c.1223C>T (p.S408L) was found. The clinical presentation of rare mutations such as RET p.S891A differed among family members carrying the same germline mutation. Our index case's more severe clinical presentation may be due to an additional somatic mutation. Sorafenib treatment can be an option for advanced MTC and may prevent disease progression.
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Inherited forms of medullary thyroid carcinoma (MTC) can cause serious problems in diagnosis and follow-up. Family screening is performed, and prophylactic thyroidectomy at an appropriate age can be life-saving. This study aimed to investigate the diagnostic, clinical, laboratory characteristics, and treatment methods of cases with rearranged during transfection ( RET) mutation in the childhood age group. Patients diagnosed with hereditary MTC and patients who were evaluated by detecting MTC and/or RET mutations in their families were included in this study. Nine cases from 6 families were included in the study. Seven patients were evaluated as a result of screening, whereas 2 patients, one of whom was MEN2B, were symptomatic. Prophylactic thyroidectomy was performed in 7 cases. Medullary microcarcinoma was found in all, and additional papillary thyroid carcinoma in one. An inoperable tumor was detected in one patient, and sorafenib treatment was applied. A very heterogeneous clinical presentation can be seen in a group of pediatric patients with RET mutation. In rare RET mutations, the genotype-phenotype relationship is still unclear, and different clinical pictures can be seen. Although prophylactic thyroidectomy is life-saving, it can cause iatrogenic hypothyroidism and hypoparathyroidism. Concomitant papillary microcarcinomas may occur in very young children with germline RET mutation.
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Neoplasia Endocrina Múltiple Tipo 2a , Neoplasias de la Tiroides , Humanos , Niño , Preescolar , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/patología , Neoplasia Endocrina Múltiple Tipo 2a/terapia , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Mutación , Tiroidectomía/métodos , Células Germinativas/patología , Proto-Oncogenes , Mutación de Línea GerminalAsunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Humanos , Niño , Nivolumab/uso terapéutico , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Mesotelioma/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patologíaRESUMEN
Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric patients with IA were included in this study. The male-to-female ratio was 42/17. The median age was 8.75 years. Hematologic malignancy was present in the majority of the patients (40/59, 68%). The mean neutropenia duration was 18.5 days. Cytosine arabinoside was the most common immunosuppressive therapy directed at T cells during IA diagnosis. IA cases were categorized as proven (27%), probable (51%), or possible (22%) according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. The lungs (78%) were the most common site of IA, and nodules were the most frequent radiological findings (75.5%). In 38 patients (64.4%) receiving antifungal prophylaxis, prophylactic agents included fluconazole (30.5%), liposomal amphotericin B (23.7%), posaconazole (8.5%), and voriconazole (1.7%). Initial treatment was most commonly administered as monotherapy (69.5%). The median antifungal treatment duration was 67 days. Eleven deaths (18.6%) were due to aspergillosis. With the increased use of corticosteroids, biological agents, and intensive immunosuppressive chemotherapy, IA will most likely continue to occur frequently in pediatric patients.
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Aspergilosis , Infecciones Fúngicas Invasoras , Humanos , Masculino , Niño , Femenino , Antifúngicos/uso terapéutico , Estudios Retrospectivos , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/diagnóstico , Voriconazol , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/epidemiologíaRESUMEN
Background: Non-Hodgkin lymphoma (NHL) includes pathologies of different clinical courses, treatments, outcomes. Our study aims to investigate the late effects of NHL survivors (NHLS). Materials and Methods: Among 59 NHL cases, 50 survivors completed their NHL treatment between 2003 and 2019. Out of 59 patients, the cumulative survival rates and event-free survival rates after 10 years since diagnosis were 82.9% ±5.2% and 84.1% ±5.2%, respectively. In addition, we compared the data related to chronic health and psychosocial conditions with their siblings (n = 61). Results: The age and gender ratios were similar in the NHLS (n = 50) and the control group (n = 61). The rate of nephrotoxicity (P = 0.02) and the frequency of admission to the hospital (P < 0.01) were significantly higher in the survivors than in the control group. Cardiotoxicity is detected in 3 (6%) of NHLS with cumulative anthracycline dose <300 mg/m2. The social status (being married [P < 0.01], having children [P = 0.003]) is impaired in NHLS. The alcohol and smoking habits, education status, and health conditions (endocrinologic, cardiac, neurological, and pulmonary) were similar in both groups. One patient had acute myeloid leukemia as a secondary malignancy. Twenty NHLS took rituximab, two of them took brentuximab vedotin plus chemotherapy. NHLS have impairment in health status, social life. Conclusion: Nephrotoxicity is a statistically more common late effect than the others in the survivors. We observe cardiotoxicity in low cumulative doses of anthracycline. A more significant number of patients is required to reveal late side effects on novel drugs.
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Cardiotoxicidad , Linfoma no Hodgkin , Adolescente , Antraciclinas/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Brentuximab Vedotina , Niño , Humanos , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Rituximab/uso terapéuticoRESUMEN
BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in immunosuppressed children. Early detection of the infection can improve prognosis in this patient population. OBJECTIVES: To investigate the utility of Aspergillus galactomannan antigen assay (GM-EIA) as a diagnostic tool for IA in at-risk paediatric patients. PATIENTS/METHODS: For the study, 659 GM-EIA results from 59 patients diagnosed with IA and 3368 GM-EIA results from 351 subjects without evidence for IA (controls) were reviewed retrospectively. Three cut-off values (i.e. ≥0.5, ≥1, ≥1.5) were specified to determine GM-EIA positivity. RESULTS: The median age was 6.3 years for boys and 14.5 years for girls. There was a significant difference between the girls and boys in terms of age (p < 0.01). For proven/probable/possible IA patients, sensitivity of 67.8% and specificity of 59.8% were detected when the ≥0.5 cut-off value was used for GM-EIA-positivity. The specificity increased to 80% at the cut-off of ≥1 and to 88% at the cut-off of ≥1.5. False positivity rates were 9.14, 3, and 1.45% at the ≥0.5, ≥1 and ≥1.5 cut-offs respectively. In the proven/probable IA group, sensitivity and negative predictive values were 86.9 and 97.2% at the ≥0.5 cut-off, 85.7 and 97.9%, at the ≥1 cut-off and 84.2 and 98.1% at ≥1.5 cut-off respectively. The positive likelihood ratio was 7.57 and the odds ratio was 42.67 at ≥1.5 cut-off. CONCLUSION: The GM-EIA may be used for both screening and diagnostic purposes in paediatric patients using a cut-off value of ≥1.5 for GM-EIA positivity.
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Aspergilosis , Infecciones Fúngicas Invasoras , Aspergilosis/diagnóstico , Niño , Femenino , Galactosa/análogos & derivados , Humanos , Infecciones Fúngicas Invasoras/diagnóstico , Masculino , Mananos , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To evaluate the risk factors leading to recurrence and new tumor (NT) development in patients with retinoblastoma after intravenous chemotherapy (IVC) and to review the treatment outcomes. MATERIALS AND METHODS: The records of 166 retinoblastoma cases (having 246 affected eyes) who underwent six-cycle IVC (vincristine, etoposide, and carboplatin) as primary treatment between October 1999 and August 2020 were reviewed retrospectively. RESULTS: The mean ages at presentation were 9.0 (median: 8.0) and 9.2 (median: 8.5) months in cases with recurrence and NTs respectively. Recurrence was detected in 40 (16.3%) eyes, NTs in 29 (11.8%), and both recurrence/NTs in 24 (9.8%). The mean time elapsed till recurrence and NT was 10.7 months. Multivariable analysis showed that the factors predictive of recurrence were largest tumor base diameter (LTBD) >12 mm (p = 0.039) and presence of subretinal seeds at diagnosis (p = 0.043). Multivariable risk factors for the development of NTs were bilateral familial retinoblastoma (p = 0.001) and presence of subretinal seeds at diagnosis (p = 0.010). Mean follow-up was 80.1 (median: 72.5) months. By Kaplan-Meier analysis, the 1-, 3-, and 6-year recurrence and NT rates were 21.2%, 28.1%, and 28.7% and 14.9%, 22.6%, and 23.9% respectively. The most common treatment methods used for recurrent and/or NTs included cryotherapy, transpupillary thermotherapy, and intra-arterial chemotherapy. Enucleation was eventually required in 24/93 (25.8%) eyes. No patient developed metastasis. DISCUSSION: Development of recurrence and/or NT after IVC was noted in 38% of all retinoblastoma eyes. Bilateral familial disease, LTBD >12 mm, and presence of subretinal seeds at baseline were risk factors for recurrence and NTs in this study.
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Neoplasias de la Retina , Retinoblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/uso terapéutico , Etopósido/uso terapéutico , Humanos , Lactante , Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Except for side effects expected standart dose use of the chemotherapeutics agents, toxic effects (poisoning) may occur if high doses of are mistakenly used in the treatment of haemato-oncological diseases and these toxic doses are usually fatal. Here, we report a case of Stevens Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) following administration of toxic dose of vinblastine by mistake. A 20-month-old male patient with a diagnosis of Langerhans Cell Histiocytosis (Letterer-Siwe) at the pediatric oncology department was admitted to intensive care unit, after having received treatment protocol consisting of vinblastine, etoposide and prednisolone, with fever, altered consciousness and decompensated shock findings. Skin biopsy which performed from bullous lesions in the perianal, neck and axillary regions was resulted compatible with SJS / TEN in the patient with multiple organ failure, at 48 h of admission. It was later determined that the patient has been mistakenly given 10 times the normal dose of vinblastine he needed (60 mg/m2), which was 6 mg/m2. Plasma exchange was performed 3 times for vinblastine toxicity, intravenous immunoglobulin was administered for SJS / TEN therapy and phenobarbital was initiated to increase drug metabolism. The patient whose clinical picture fully improved, was transferred to the oncology department on the 30th day of intensive care hospitalization. Vinblastine toxicity is a life-threatening condition that can cause multiple organ failure, SJS / TEN. Plasma exchange is an effective treatment method for the removal of vinblastine from the body and in these cases of toxicity.
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Inmunoglobulinas Intravenosas/uso terapéutico , Piel/efectos de los fármacos , Síndrome de Stevens-Johnson/etiología , Vinblastina/efectos adversos , Biopsia , Etopósido/administración & dosificación , Etopósido/efectos adversos , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Humanos , Lactante , Masculino , Fenobarbital , Intercambio Plasmático , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Piel/patología , Síndrome de Stevens-Johnson/tratamiento farmacológico , Resultado del TratamientoRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Aim: The main purpose of this study is to determine the current status of long-term follow-up (LTFU) for childhood cancer survivors and the challenges of LTFU for pediatric cancer survivors at pediatric oncology institutions in Turkey. Material and methods: A questionnaire was e-mailed to the directors of 33 pediatric oncology centers (POCs) registered in the Turkish Pediatric Oncology Group (TPOG). Of these 33 active TPOG institutions, 21 participated in the study and returned their completed questionnaires. Results: Only 1 of the 21 participating centers had a separate LTFU clinic. The remaining centers provided LTFU care for childhood cancer survivors at the pediatric oncology outpatient clinic. Of these centers, 17 (80.9%) reported difficulty in transition from the pediatric clinic to the adult clinic, 14 (66.6%) reported insufficient care providers, and 12 (57.1%) reported insufficient time and transportation problems. As neglected late effects, 16 (76.1%) centers reported psychosocial and getty job problems and 11 (52.3%) reported sexual and cognitive problems. None of the centers had their own LTFU guidelines for their daily LTFU practice Conclusion: This study was the first to gain an overview of the needs of POCs and the gaps in survivorship services in Turkey. The results from this study will help to develop a national health care system and national guidelines for pediatric cancer survivors.
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Cuidados Posteriores/métodos , Supervivientes de Cáncer/estadística & datos numéricos , Países en Desarrollo , Pediatría/métodos , Encuestas y Cuestionarios/estadística & datos numéricos , Niño , Estudios Transversales , Humanos , Transición a la Atención de Adultos , TurquíaRESUMEN
OBJECTIVES: To evaluate the long-term treatment outcomes in intraocular retinoblastoma (RB) including the associated factors for eventual treatment with external beam radiotherapy (EBRT) and enucleation as well as to analyse the risk factors for metastasis and death in extraocular RB. METHODS: Retrospective analysis of 390 eyes from 256 (89.8%) intraocular RB and 29 (10.2%) extraocular RB cases diagnosed and treated between October 1998 and May 2018 at one of the largest tertiary care centers in Turkey. RESULTS: Of 351 intraocular RB eyes, 53.3% had group D/E disease at presentation. 75 (21.4%) of 351 eyes underwent primary enucleation. Of the remaining 276 eyes undergoing eye-conserving treatments, 201 (72.8%) were salvaged. Most of these eyes were treated using intravenous chemotherapy and/or focal treatments [transpupillary thermotherapy (TTT) and cryotherapy] initially. EBRT was eventually required in 48 (17.4%) eyes and secondary enucleation in 75 (27.2%) eyes. At mean follow-ups of 76.7 and 39.7 months for intraocular and extraocular RB cohorts, respectively, 180 (46.2%) eyes underwent primary/secondary enucleation and exenteration. Overall, 13 cases developed metastasis and 9 died. Two patients with trilateral RB also expired. Multivariable risk factors for enucleation were the presence of vitreous seeds (p < 0.001), absence of EBRT administration (p = 0.033), 5-9 TTT applications compared with no TTT (p = 0.031), and each 1 mm increase in tumour base diameter (p < 0.001). Univariate factors predictive of metastasis were the presence of extraocular RB detected by imaging methods (p < 0.001) and extrascleral/optic nerve cut end involvement at histopathological examination (p < 0.001). CONCLUSIONS: In our series, 72.8% of the intraocular RB eyes undergoing eye-conserving treatments were saved. The globe salvage rate for all intraocular and extraocular RB eyes was 53.8% and the overall survival rate was 96.1%.
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Neoplasias de la Retina , Retinoblastoma , Protocolos de Quimioterapia Combinada Antineoplásica , Enucleación del Ojo , Humanos , Lactante , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Estudios Retrospectivos , Resultado del Tratamiento , TurquíaRESUMEN
BACKGROUND: The immunomodulator mifamurtide plus a chemotherapy regimen has been shown to significantly improve the outcome in non-metastatic osteosarcoma patients. We report the results of the addition of mifamurtide to chemotherapy in newly diagnosed patients with osteosarcoma. METHODS: A total of 36 children with osteosarcoma without detectable metastasis were treated between November 2010 and April 2018 at the Ankara University Department of Pediatric Oncology. Mifamurtide was added to the chemotherapy regimen in 17 patients while the remaining 19 did not receive mifamurtide. The probabilities of metastasis and overall survival were compared between the groups. RESULTS: The 43-month survival rate was 87.5% and 89.9% in the patients who received and did not receive mifamurtide, respectively (p=0.65). Common side effects of mifamurtide were chills and fever. The addition of mifamurtide in the high-risk group with ≤95% necrosis tended to decrease the probability of distant metastasis (36.4% vs. 58.3%) (p=0.39). The time to metastasis in the group with positive surgical margins (4 months in one patient in the non-mifamurtide group, 7 and 20 months in the mifamurtide group) was also longer in the mifamurtide group. During the 43-month follow up period, median time to metastasis was longer in the mifamurtide group (20 vs. 5 months). In addition, mifamurtide plus chemotherapy decreased the risk of metastasis in the cases with primary site relapse. CONCLUSIONS: The addition of mifamurtide to chemotherapy might improve event-free survival by decreasing the probability of distant metastasis in bad histologic responders, and also by increasing the time to distant metastasis in the surgical margin positive group. Additional clinical studies are necessary to determine the long-term effects of mifamurtide on metastatic disease.
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Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Fosfatidiletanolaminas/uso terapéutico , Acetilmuramil-Alanil-Isoglutamina/efectos adversos , Acetilmuramil-Alanil-Isoglutamina/uso terapéutico , Adolescente , Niño , Humanos , Metástasis de la Neoplasia , Osteonecrosis/inducido químicamente , Fosfatidiletanolaminas/efectos adversos , RecurrenciaRESUMEN
Taçyildiz N, Tanyildiz HG, Ünal E, Dinçaslan H, Asarcikli F, Adakli Aksoy B, Vatansever G, Yavuz G. A targeted salvage therapy with Brentuximab vedotin in heavily treated refractory or relapsed pediatric Hodgkin lymphoma patients before and after stem cell transplantation. Turk J Pediatr 2019; 61: 671-676. Hodgkin`s lymphoma (HL) is highly curable disease in its early stages, but in advanced stages, it presents a dilemma when it becomes refractory or relapses after several rounds of chemotherapy. Brentuximab vedotin (BV) is an antibody-drug conjugate that targets the tumor necrosis receptor family protein member CD30 positive malignancies via an anti-CD30 monoclonal antibody linked to monomethyl auristatin-E. In adult and pediatric studies, it has been shown to be an effective salvage therapy for primary refractory HL or relapse after autologous stem cell transplant (ASCT). Between July 2012 and August 2017, we administered BV (1.8 mg/m2 every three weeks; 12 cycles totally) with doxorubucin, vinblastin, dacarbazine (AVD), rituximab + ifosfamide + carboplatin + etoposide (RICE), or bendamustine combination treatment in pediatric HL patients, who were previosuly treated for refractory or relapsed advanced stage HL before (seven patients) or after (one patient) ASCT in our center. After eight BV courses, one patient was able to undergo match unrelated donor (MUD) SCT. Another seven pediatric HL patients, who were not able to go into remission with any other classical HL chemotherapy protocols, received 4-6 courses of BV-AVD and/or RICE/bendamustine. All were able to undergo ASCT after negative positron emission tomography (PET) imaging results. After ASCT, we switched to BV as consolidation therapy until a total of 12 cycles was completed. Patients went into remission after a median 34 (range: 12-42) months from the start of BV treatment. BV is an encouraging, well- tolerated, and effective targeted therapy especially when combined with AVD or when alternated with another targeted therapy combination, including RICE, when needed.
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Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Terapia Recuperativa/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Aims: Survivin is involved in the inhibition of apoptosis and the regulation of cell division. In addition to wild-type survivin (survivin-wt), at least four splice variants with differential functions (ΔEx3 and 3B antiapoptotic, and 2α and 2B proapoptotic) have been identified. Survivin is highly expressed in several cancers, including hematological malignancies. Although acute lymphoblastic leukemia (ALL) is the most frequent malignancy in children, studies that investigated survivin expression in ALL are limited, and there is no study on 3B and 2α expression in ALL. Therefore the expression of survivin-wt and its splice variants was investigated in pediatric B-cell ALL patients. Materials and Methods: The expression of survivin-wt and its four splice variants was investigated by quantitative real-time polymerase chain reaction in archival RNA samples of 35 pediatric B-cell ALL patients. Patients were divided into high- and standard-risk groups according to age, white blood cell count, extramedullary involvement, and genetic risk factors; expression of survivin variants was compared between these two risk groups. Results: We found that the ratio of survivin-ΔEx3/wild type (WT) expression was higher in the low-risk group than in the high-risk group. Conclusion: Comparative analysis between the high- and low-risk B-cell ALL groups indicated that the survivin-ΔEx3/WT expression ratio could potentially be used in risk classification for pediatric B-cell ALL.
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Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Survivin/genética , Adolescente , Biomarcadores de Tumor , Niño , Preescolar , Cartilla de ADN , Exones/genética , Femenino , Regulación Leucémica de la Expresión Génica , Humanos , Lactante , Intrones/genética , Masculino , Proteínas de Neoplasias/biosíntesis , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Riesgo , Survivin/biosíntesisRESUMEN
The aim of the present study was to evaluate the efficiency and side effects of mifamurtide in childhood osteosarcoma (OS). In total, 477 doses of 2 mg/m intravenous (IV) mifamurtide, along with paracetamol as a premedication, were given to 15 patients with primary nonmetastatic OS after complete surgical resection and to 3 patients with progressive OS. The most common side effects encountered in the patients were chills and fever (17/18). These reactions were observed in 4 patients during the administration of each dose, in a single patient during the last administration, and in the remaining 12 patients during the first or initial 2 administrations. Headache, myalgia, and arthralgia were observed in 2 patients during each infusion. Headache was observed in 1 patient with additional hearing loss during the first 2 infusions. One patient had back pain occuring within the first infusion. Of the 15 patients with primary nonmetastatic OS and treated with the addition of mifamurtide to chemotherapy, 13 showed a complete remission, and 2 patients were still under treatment with a complete remission. Of 3 patients with progressive disease, 2 died while the disease progressed further in the third case over a 51-month period. The 3-year overall survival and event-free survival distributions were 87.5% (mean follow-up time, 46.12; 95% confidence interval, 37.79-52.45 mo) and 75.6% (mean follow-up time, 31.30; 95% confidence interval, 26.54-36.06 mo), respectively. We consider that mifamurtide therapy is a safe and well-tolerated agent in childhood OS.