Detection of N-Glycolyl GM3 Ganglioside in Neuroectodermal Tumors by Immunohistochemistry: An Attractive Vaccine Target for Aggressive Pediatric Cancer

The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 μm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy

Tridimensional Retinoblastoma Cultures as Vitreous Seeds Models for Live-Cell Imaging of Chemotherapy Penetration

A preclinical model could aid in understanding retinoblastoma vitreous seeds behavior, drug penetration, and response to chemotherapy to optimize patient treatment. Our aim was to develop a tridimensional in vitro model of retinoblastoma vitreous seeds to assess chemotherapy penetration by means of live-cell imaging. Cell cultures from patients with retinoblastoma who underwent upfront enucleation were established and thoroughly characterized for authentication of human tumor origin. The correlation of the in vitro tridimensional structures resembling human spheres and dusts vitreous seeds was established. Confocal microscopy was used to quantify real-time fluorescence of topotecan as a measure of its penetration into different sizes of spheres. Cell viability was determined after chemotherapy penetration. The in vitro spheres and dusts models were able to recapitulate the morphology, phenotype, and genotype of patient vitreous seeds. The larger the size of the spheres, the longer the time required for the drug to fully penetrate into the core (p < 0.05). Importantly, topotecan penetration correlated with its cytotoxic activity. Therefore, the studied tridimensional cell model recapitulated several characteristics of vitreous seeds observed in patients with retinoblastoma and were successfully used to assess live-cell imaging of chemotherapy penetration for drug distribution studies.Fil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aschero, María del Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fuentes, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Buontempo, Fabian. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Zugbi, Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sgroi, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Abramson, David H.. Memorial Sloan-kettering Cancer Center; Estados UnidosFil: Carcaboso, Angel M.. Hospital Sant Joan de Deu Barcelona; EspañaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Treatment of nonmetastatic unilateral retinoblastoma in children

IMPORTANCE: Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management. OBJECTIVE: To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria. DESIGN, SETTING, AND PARTICIPANTS: This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017. INTERVENTIONS: Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10mg/m2/d], and vincristine sulfate [0.05mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500mg/m2/d, days 1 and 2] and etoposide [100mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles. MAIN OUTCOMES AND MEASURES: Probability of event-free survival (extraocular relapse and death from any cause were considered events). RESULTS: Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95%CI, 0.94-0.99), and the probability of overall survival was 0.98 (95%CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death). CONCLUSIONS AND RELEVANCE: Adjuvant therapymay be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.Fil: Pérez, Verónica. Hospital San Juan de Dios; ChileFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Rey, Guadalupe. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Parareda Salles, Andreu. Hospital Sant Joan de Déu; EspañaFil: Kopp, Katherine. Hospital Dr. Luis Calvo Mackenna Hospital; ChileFil: Dabezies, Agustín P.. Hospital Pereyra Rossell; UruguayFil: Dufort, Gustavo. Hospital Pereyra Rossell; UruguayFil: Zelter, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: López, Juan P.. Hospital Calvo Mackenna; ChileFil: Urbieta, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Alcalde Ruiz, Elisa. Hospital Dr. Luis Calvo Mackenna Hospital; ChileFil: Catala Mora, Jaume. Hospital Sant Joan de Déu; EspañaFil: Suñol, Mariona. Hospital Sant Joan de Déu; EspañaFil: Ossandon, Diego. Hospital San Juan de Dios; ChileFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Croxatto, Juan Oscar. Fundación Oftalmología Argentina "J. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Dávila, María T. G.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Reaman, Gregory. Center for Drug Evaluation and Research; Estados UnidosFil: Ravindranath, Yaddanapudi. Children’s Hospital of Michigan; Estados UnidosFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Recurrent somatic chromosomal abnormalities in relapsed extraocular retinoblastoma

Most reports about copy number alterations (CNA) in retinoblastoma relate to patients with intraocular disease and features of children with extraocular relapse remain unknown, so we aimed to describe the CNA in this population. We evaluated 23 patients and 27 specimens from 4 centers. Seventeen cases had extraocular relapse after initial enucleation and six cases after an initial preservation attempt. We performed an analysis of CNA and BCOR gene alteration by SNP array (Single Nucleotide Polymorfism array), whole-exome sequencing, IMPACT panel and CGH array (Array-based comparative genomic hybridization). All cases presented CNA at a higher prevalence than those reported in previously published studies for intraocular cases. CNA previously reported for intraocular retinoblastoma were found at a high frequency in our cohort: gains in 1q (69.5%), 2p (60.9%) and 6p (86.9%), and 16q loss (78.2%). Other, previously less-recognized, CNA were found including loss of 11q (34.8%), gain of 17q (56.5%), loss of 19q (30.4%) and BCOR alterations were present in 72.7% of our cases. A high number of CNA including 11q deletions, 17q gains, 19q loss, and BCOR alterations, are more common in extraocular retinoblastoma. Identification of these features may be correlated with a more aggressive tumor warranting consideration for patient management.Fil: Aschero, María del Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Francis, Jasmine H.. Memorial Sloan-Kettering Cancer Center; Estados UnidosFil: Ganiewich, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Gomez Gonzalez, Soledad. Hospital Sant Joan de Deu Barcelona; EspañaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Zugbi, Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ottaviani, Daniela. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lemelle, Lauriane. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Mena, Marcela Daniela C. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Correa Llano, Genoveva. Hospital Sant Joan de Deu Barcelona; EspañaFil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Szijan, Irene. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Mora, Jaume. Hospital Sant Joan de Deu Barcelona; EspañaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Doz, François. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Radvanyi, François. Universite de Paris; Francia. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Abramson, David H.. Memorial Sloan-Kettering Cancer Center; Estados UnidosFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Hospital Sant Joan de Deu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Early impact of the COVID-19 pandemic on paediatric cancer care in Latin America

Although previous studies have suggested that the complications and mortality rate related to COVID-19 are substantially lower in the paediatric population,1 it is reasonable to consider that children with underlying conditions such as cancer will be at increased risk of severe disease...Fil: Vasquez, Liliana. Universidad de San Martín de Porres; Perú. Organización Panamericana de la Salud; PerúFil: Sampor, Claudia. Fundacion Hospital de Pediatria Professor Dr. Juan P. Garrahan; ArgentinaFil: Villanueva, Gabriela. Fundacion Hospital de Pediatria Professor Dr. Juan P. Garrahan; ArgentinaFil: Maradiegue, Essy. Instituto Nacional de Enfermedades Neoplasicas; PerúFil: Garcia Lombardi, Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gomez García, Wendy. Hospital Infantil Dr. Robert Reid Cabral; República DominicanaFil: Moreno, Florencia. Ministerio de Salud. Instituto Nacional del Cáncer; ArgentinaFil: Diaz, Rosdali. Instituto Nacional de Enfermedades Neoplasicas; PerúFil: Cappellano, Andrea M.. Universidade Federal de Sao Paulo; BrasilFil: Portilla, Carlos Andres. Universidad del Valle; ColombiaFil: Salas, Beatriz. Hospital del Niño Manuel Ascencio Villarroel; BoliviaFil: Nava, Evelinda. Hospital de Niños Jesus Garcia Coello; VenezuelaFil: Brizuela, Silvia. Instituto de Previsión Social ; ParaguayFil: Jimenez, Soledad. Hospital Solca Núcleo de Loja; EcuadorFil: Espinoza, Ximena. Hospital de Niños Dr. Roberto del Río; ChileFil: Gassant, Pascale Yola. Hôpital Saint-Damien; HaitíFil: Quintero, Karina. Children's Hospital Dr Jose Renan Esquivel; PanamáFil: Fuentes Alabi, Soad. Hospital Nacional de Niños Benjamin Bloom; El SalvadorFil: Velasquez, Thelma. No especifíca;Fil: Fu, Ligia. Hospital Escuela de Tegucigalpa; HondurasFil: Gamboa, Yessika. National Children's Hospital; Costa RicaFil: Quintana, Juan. Clinica Las Condes; ChileFil: Castiglioni, Mariela. Hospital Pereira Rossell; UruguayFil: Nuñez, Cesar. Children's Cancer Hospital; Estados UnidosFil: Moreno, Arturo. Hospital Universitario de Puebla; MéxicoFil: Luna Fineman, Sandra. State University of Colorado at Boulder; Estados UnidosFil: Luciani, Silvana. Pan American Health Organization; Estados UnidosFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Hospital Sant Joan de Deu Barcelona; Españ

Clinical, genomic, and pharmacological study of MYCN-amplified RB1 wild-type metastatic retinoblastoma

An uncommon subgroup of unilateral retinoblastomas with highly aggressive histological features, lacking aberrations in RB1 gene with high-level amplification of MYCN (MCYNampl RB1+/+) has only been described as intra-ocular cases treated with initial enucleation. Here, we present a comprehensive clinical, genomic, and pharmacological analysis of two cases of MCYNampl RB1+/+ with orbital and cervical lymph node involvement, but no central nervous system spread, rapidly progressing to fatal disease due to chemoresistance. Both patients showed in common MYCN high amplification and chromosome 16q and 17p loss. A somatic mutation in TP53, in homozygosis by LOH, and high chromosomal instability leading to aneuploidy was identified in the primary ocular tumor and sites of dissemination of one patient. High-throughput pharmacological screening was performed in a primary cell line derived from the lymph node dissemination of one case. This cell line showed resistance to broad spectrum chemotherapy consistent with the patient’s poor response but sensitivity to the synergistic effects of panobinostat–bortezomib and carboplatin–panobinostat associations. From these cells we established a cell line derived xenograft model that closely recapitulated the tumor dissemination pattern of the patient and served to evaluate whether triple chemotherapy significantly prolonged survival of the animals. We report novel genomic alterations in two cases of metastatic MCYNampl RB1+/+ that may be associated with chemotherapy resistance and in vitro/in vivo models that serve as basis for tailoring therapy in these cases.Fil: Zugbi, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ganiewich, Daiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Bhattacharyya, Arpita. Tata Memorial Hospital; IndiaFil: Aschero, María del Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ottaviani, Daniela. Centre National de la Recherche Scientifique; FranciaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Mena, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sgroi, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Suñol, Mariona. Hospital Sant Joan de Deu Barcelona; EspañaFil: Daroqui, Manuel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Baialardo, Edgardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Salas, Beatriz. Hospital Asencio Villaroel; BoliviaFil: Das, Anirban. Tata Memorial Hospital; IndiaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Francis, Jasmine H.. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Garippa, Ralph. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Abramson, David. Memorial Sloan-kettering Cancer Center.; Estados UnidosFil: Radvanyi, François. Centre National de la Recherche Scientifique; FranciaFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Comparison of the pharmacological activity of idarubicin and doxorubicin for retinoblastoma

Fil: Zugbi, Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castañon, Agustina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Minimally disseminated disease and outcome in overt orbital retinoblastoma

In this retrospective study of patients with overt orbital retinoblastoma, we evaluated minimally disseminated disease (MDD) in bone marrow and cerebrospinal fluid (CSF) using CRX and/or GD2 synthase as markers. Ten patients were evaluated five (50%) at diagnosis and five upon relapse. MDD was detected in four cases (one in the bone marrow, two in the CSF, and in one case in both sites). All patients received chemotherapy and four received orbital radiotherapy. Seven patients relapsed or progressed and all of them died. Three patients remain in complete remission. There was no apparent correlation between MDD and the outcome.Fil: Aschero, Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Torbidoni, Ana Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Laurent, Viviana Eunice. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zugbi, Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Alonso, Daniel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

A phase I study of the anti-idiotype vaccine racotumomab in neuroblastoma and other pediatric refractory malignancies

BACKGROUND: Pediatric neuroectodermal malignancies express N-glycolylated gangliosides including N-glycolyl GM3 (NeuGcGM3) as targets for immunotherapy. PROCEDURE: We evaluated the toxicity and maximum tolerated dose and immunological response of racotumomab, an anti-idiotype vaccine targeting NeuGcGM3 through a Phase I study enrolling children with relapsed or resistant tumors expressing NeuGcGM3. MATERIALS AND METHODS: Drug dose was escalated to three levels (0.15-0.25-0.4 mg) of racotumomab administered intradermally. Each drug level included three patients receiving a total of three doses, every 14 days. A confirmation cohort was added to the highest dose level. Antibody response was assessed upon study entry and at 4-week intervals for at least three immunological determinations for each patient. RESULTS: Fourteen patients were enrolled (10 with neuroblastoma, one with retinoblastoma, one with Wilms' tumor, and two with brainstem glioma). Three patients completed the three drug levels and three were enrolled in the confirmation cohort. One patient died of tumor progression before completing the three applications. Racotumomab was well tolerated. The only side effect observed was grade 1-2 toxicity at the injection site. Racotumomab elicited an IgM and/or IgG antibody response directed against NGcGM3 in nine patients and IgM against racotumomab in 11 of 13 evaluable patients. The maximum tolerated dose was not reached and no dose-limiting toxicity was seen. CONCLUSIONS: Racotumomab vaccination has a favorable toxicity profile up to a dose of 0.4 mg, and most patients elicited an immune response. Its activity as immunotherapy for neuroectodermal malignancies will be tested in further clinical trials.Fil: Cacciavillano, Walter. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Venier, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Gabri, Mariano Rolando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Davila, María Teresa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Galluzzo, María L.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Guthmann, Marcelo D.. Laboratorio ELEA; ArgentinaFil: Fainboim, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin