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1. Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Author

Mukkada, S, Bhakta, N, Chantada, G, Chen, Y, Vedaraju, Y, Faughnan, L, Homsi, M, Muniz-Talavera, H, Ranadive, R, Metzger, M, Friedrich, P, Agulnik, A, Jeha, S, Lam, C, Dalvi, R, Hessissen, L, Moreira, D, Santana, V, Sullivan, M, Bouffet, E, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Ribelles, A, Balduzzi, A, Elhaddad, A, Casanovas, A, Garcia Velazquez, A, Laptsevich, A, Chang, A, F. Sampaio A., L, Gonzalez Prieto, A, Lassaletta, A, Suarez M, A, Alcasabas, A, Colita, A, Morales La Madrid, A, Samudio, A, Tondo, A, Colombini, A, Kattamis, A, Lopez Facundo, N, Bhattacharyya, A, Alimi, A, Phulpin, A, Vakrmanova, B, Aksoy, B, Brethon, B, Kobuin, J, Nolasco Monteiro, C, Paillard, C, Vezina, C, Ceyhun, B, Hentea, C, Meazza, C, Ortiz-Morales, D, Solorzano, R, Arce Cabrera, D, Zama, D, Ghosh, D, Ramirez-Rivera, D, Calle Jara, D, Janic, D, Rey Helo, E, Gouache, E, Guerrero Quiroz, E, Lopez, E, Thebault, E, Maradiegue, E, de Berranger, E, Ebeid, F, Galaverna, F, Antillon-Klussmann, F, Espinoza Chacur, F, Negro, F, Carraro, F, Compagno, F, Barriga, F, Tamayo Pedraza, G, Sanchez Fernandez, G, Naidu, G, Tokuc, G, Alias, H, B Segocio, H, Boudiaf, H, Asetre Luna, I, Maia, I, Astigarraga, I, Maza, I, Montoya Vasquez, J, Jazbec, J, Lazic, J, Beck Dean, J, Rouger-Gaudichon, J, Contreras Gonzalez, J, Huerta Aragones, J, Fuster, J, Quintana, J, Palma, J, Svojgr, K, Quintero, K, Malic Tudor, K, Georgantzi, K, P Schultz, K, Urena Horno, L, Fraquelli, L, Meneghello, L, Shalaby, L, Macias Mora, L, A Renner, L, Nunes Silva, L, Sisinni, L, Hammad, M, Fernandez Sanmartin, M, Zubieta A, C, Drozdowski, M, Kourti, M, Palladino, M, Miranda Madrazo, M, Poiree, M, Popova, M, Melgar, M, Baragano, M, Aviles-Robles, M, Provenzi, M, Mendes Lins, M, Fatih Orhan, M, Villarroel, M, Jeronimo, M, Varas Palma, M, Rafie Raza, M, M Justin, M, Shaheen, N, Dominguez-Pinilla, N, Whipple, N, Andre, N, Hrusak, O, Velasco Puyo, P, Zacasa Vargas, P, Olate Mellado, P, Yola Gassant, P, Diaz Romero, P, De Santis, R, Kebudi, R, Boranbayeva, R, Vasquez, R, Segura, R, Rosado, R, Gomez, S, Raimbault, S, Gunasekera, S, Makkeyah, S, Buyukkapu Bay, S, M Gomez, S, Bouttefroy, S, Islam, S, Abouelnaga, S, Torres, S, Cesaro, S, Nunes, S, Rouxinol, S, Bhaumik, S, Saliyeva, S, Inostroza, T, Velasquez, T, Hnin, T, Noren-Nystrom, U, Baretta, V, Jimenez-Antolinez, Y, Perez Alonso, V, Ayer Miller, V, Gandemer, V, Lotero, V, Mishkova, V, Gomez-Garcia, W, Margaryan, Y, Syed, Y, Mukkada S., Bhakta N., Chantada G. L., Chen Y., Vedaraju Y., Faughnan L., Homsi M. R., Muniz-Talavera H., Ranadive R., Metzger M., Friedrich P., Agulnik A., Jeha S., Lam C., Dalvi R., Hessissen L., Moreira D. C., Santana V. M., Sullivan M., Bouffet E., Caniza M. A., Devidas M., Pritchard-Jones K., Rodriguez-Galindo C., Ribelles A. J., Balduzzi A., Elhaddad A., Casanovas A., Garcia Velazquez A., Laptsevich A., Chang A., F. Sampaio A. L., Gonzalez Prieto A., Lassaletta A., Suarez M A., Alcasabas A. P., Colita A., Morales La Madrid A., Samudio A., Tondo A., Colombini A., Kattamis A., Lopez Facundo N. A., Bhattacharyya A., Alimi A., Phulpin A., Vakrmanova B., Aksoy B. A., Brethon B., Kobuin J. B., Nolasco Monteiro C., Paillard C., Vezina C., Ceyhun B., Hentea C., Meazza C., Ortiz-Morales D., Solorzano R. D., Arce Cabrera D., Zama D., Ghosh D., Ramirez-Rivera D., Calle Jara D. A., Janic D., Rey Helo E., Gouache E., Guerrero Quiroz E., Lopez E., Thebault E., Maradiegue E., de Berranger E., Ebeid F. S. E., Galaverna F., Antillon-Klussmann F., Espinoza Chacur F., Negro F. D., Carraro F., Compagno F., Barriga F., Tamayo Pedraza G., Sanchez Fernandez G., Naidu G., Tokuc G., Alias H., B Segocio H. G., Boudiaf H., Asetre Luna I., Maia I., Astigarraga I., Maza I., Montoya Vasquez J. E., Jazbec J., Lazic J., Beck Dean J., Rouger-Gaudichon J., Contreras Gonzalez J. C., Huerta Aragones J., Fuster J. L., Quintana J., Palma J., Svojgr K., Quintero K., Malic Tudor K., Georgantzi K., P Schultz K. A., Urena Horno L., Fraquelli L., Meneghello L., Shalaby L., Macias Mora L. L., A Renner L., Nunes Silva L., Sisinni L., Hammad M., Fernandez Sanmartin M., Zubieta A C. M., Drozdowski M. C., Kourti M., Palladino M. M., Miranda Madrazo M. R., Poiree M., Popova M., Melgar M., Baragano M., Aviles-Robles M. J., Provenzi M., Mendes Lins M., Fatih Orhan M., Villarroel M., Jeronimo M., Varas Palma M., Rafie Raza M., M Justin M., Shaheen N., Dominguez-Pinilla N., Whipple N. S., Andre N., Hrusak O., Velasco Puyo P., Zacasa Vargas P., Olate Mellado P., Yola Gassant P., Diaz Romero P., De Santis R., Kebudi R., Boranbayeva R., Vasquez R., Segura R. A., Rosado R. E., Gomez S., Raimbault S., Gunasekera S., Makkeyah S. M., Buyukkapu Bay S., M Gomez S., Bouttefroy S., Islam S., Abouelnaga S., Torres S. F., Cesaro S., Nunes S., Rouxinol S., Bhaumik S., Saliyeva S., Inostroza T., Velasquez T., Hnin T. M., Noren-Nystrom U., Baretta V., Jimenez-Antolinez Y. V., Perez Alonso V., Ayer Miller V., Gandemer V., Lotero V., Mishkova V., Gomez-Garcia W., Margaryan Y., Syed Y., Mukkada, S, Bhakta, N, Chantada, G, Chen, Y, Vedaraju, Y, Faughnan, L, Homsi, M, Muniz-Talavera, H, Ranadive, R, Metzger, M, Friedrich, P, Agulnik, A, Jeha, S, Lam, C, Dalvi, R, Hessissen, L, Moreira, D, Santana, V, Sullivan, M, Bouffet, E, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Ribelles, A, Balduzzi, A, Elhaddad, A, Casanovas, A, Garcia Velazquez, A, Laptsevich, A, Chang, A, F. Sampaio A., L, Gonzalez Prieto, A, Lassaletta, A, Suarez M, A, Alcasabas, A, Colita, A, Morales La Madrid, A, Samudio, A, Tondo, A, Colombini, A, Kattamis, A, Lopez Facundo, N, Bhattacharyya, A, Alimi, A, Phulpin, A, Vakrmanova, B, Aksoy, B, Brethon, B, Kobuin, J, Nolasco Monteiro, C, Paillard, C, Vezina, C, Ceyhun, B, Hentea, C, Meazza, C, Ortiz-Morales, D, Solorzano, R, Arce Cabrera, D, Zama, D, Ghosh, D, Ramirez-Rivera, D, Calle Jara, D, Janic, D, Rey Helo, E, Gouache, E, Guerrero Quiroz, E, Lopez, E, Thebault, E, Maradiegue, E, de Berranger, E, Ebeid, F, Galaverna, F, Antillon-Klussmann, F, Espinoza Chacur, F, Negro, F, Carraro, F, Compagno, F, Barriga, F, Tamayo Pedraza, G, Sanchez Fernandez, G, Naidu, G, Tokuc, G, Alias, H, B Segocio, H, Boudiaf, H, Asetre Luna, I, Maia, I, Astigarraga, I, Maza, I, Montoya Vasquez, J, Jazbec, J, Lazic, J, Beck Dean, J, Rouger-Gaudichon, J, Contreras Gonzalez, J, Huerta Aragones, J, Fuster, J, Quintana, J, Palma, J, Svojgr, K, Quintero, K, Malic Tudor, K, Georgantzi, K, P Schultz, K, Urena Horno, L, Fraquelli, L, Meneghello, L, Shalaby, L, Macias Mora, L, A Renner, L, Nunes Silva, L, Sisinni, L, Hammad, M, Fernandez Sanmartin, M, Zubieta A, C, Drozdowski, M, Kourti, M, Palladino, M, Miranda Madrazo, M, Poiree, M, Popova, M, Melgar, M, Baragano, M, Aviles-Robles, M, Provenzi, M, Mendes Lins, M, Fatih Orhan, M, Villarroel, M, Jeronimo, M, Varas Palma, M, Rafie Raza, M, M Justin, M, Shaheen, N, Dominguez-Pinilla, N, Whipple, N, Andre, N, Hrusak, O, Velasco Puyo, P, Zacasa Vargas, P, Olate Mellado, P, Yola Gassant, P, Diaz Romero, P, De Santis, R, Kebudi, R, Boranbayeva, R, Vasquez, R, Segura, R, Rosado, R, Gomez, S, Raimbault, S, Gunasekera, S, Makkeyah, S, Buyukkapu Bay, S, M Gomez, S, Bouttefroy, S, Islam, S, Abouelnaga, S, Torres, S, Cesaro, S, Nunes, S, Rouxinol, S, Bhaumik, S, Saliyeva, S, Inostroza, T, Velasquez, T, Hnin, T, Noren-Nystrom, U, Baretta, V, Jimenez-Antolinez, Y, Perez Alonso, V, Ayer Miller, V, Gandemer, V, Lotero, V, Mishkova, V, Gomez-Garcia, W, Margaryan, Y, Syed, Y, Mukkada S., Bhakta N., Chantada G. L., Chen Y., Vedaraju Y., Faughnan L., Homsi M. R., Muniz-Talavera H., Ranadive R., Metzger M., Friedrich P., Agulnik A., Jeha S., Lam C., Dalvi R., Hessissen L., Moreira D. C., Santana V. M., Sullivan M., Bouffet E., Caniza M. A., Devidas M., Pritchard-Jones K., Rodriguez-Galindo C., Ribelles A. J., Balduzzi A., Elhaddad A., Casanovas A., Garcia Velazquez A., Laptsevich A., Chang A., F. Sampaio A. L., Gonzalez Prieto A., Lassaletta A., Suarez M A., Alcasabas A. P., Colita A., Morales La Madrid A., Samudio A., Tondo A., Colombini A., Kattamis A., Lopez Facundo N. A., Bhattacharyya A., Alimi A., Phulpin A., Vakrmanova B., Aksoy B. A., Brethon B., Kobuin J. B., Nolasco Monteiro C., Paillard C., Vezina C., Ceyhun B., Hentea C., Meazza C., Ortiz-Morales D., Solorzano R. D., Arce Cabrera D., Zama D., Ghosh D., Ramirez-Rivera D., Calle Jara D. A., Janic D., Rey Helo E., Gouache E., Guerrero Quiroz E., Lopez E., Thebault E., Maradiegue E., de Berranger E., Ebeid F. S. E., Galaverna F., Antillon-Klussmann F., Espinoza Chacur F., Negro F. D., Carraro F., Compagno F., Barriga F., Tamayo Pedraza G., Sanchez Fernandez G., Naidu G., Tokuc G., Alias H., B Segocio H. G., Boudiaf H., Asetre Luna I., Maia I., Astigarraga I., Maza I., Montoya Vasquez J. E., Jazbec J., Lazic J., Beck Dean J., Rouger-Gaudichon J., Contreras Gonzalez J. C., Huerta Aragones J., Fuster J. L., Quintana J., Palma J., Svojgr K., Quintero K., Malic Tudor K., Georgantzi K., P Schultz K. A., Urena Horno L., Fraquelli L., Meneghello L., Shalaby L., Macias Mora L. L., A Renner L., Nunes Silva L., Sisinni L., Hammad M., Fernandez Sanmartin M., Zubieta A C. M., Drozdowski M. C., Kourti M., Palladino M. M., Miranda Madrazo M. R., Poiree M., Popova M., Melgar M., Baragano M., Aviles-Robles M. J., Provenzi M., Mendes Lins M., Fatih Orhan M., Villarroel M., Jeronimo M., Varas Palma M., Rafie Raza M., M Justin M., Shaheen N., Dominguez-Pinilla N., Whipple N. S., Andre N., Hrusak O., Velasco Puyo P., Zacasa Vargas P., Olate Mellado P., Yola Gassant P., Diaz Romero P., De Santis R., Kebudi R., Boranbayeva R., Vasquez R., Segura R. A., Rosado R. E., Gomez S., Raimbault S., Gunasekera S., Makkeyah S. M., Buyukkapu Bay S., M Gomez S., Bouttefroy S., Islam S., Abouelnaga S., Torres S. F., Cesaro S., Nunes S., Rouxinol S., Bhaumik S., Saliyeva S., Inostroza T., Velasquez T., Hnin T. M., Noren-Nystrom U., Baretta V., Jimenez-Antolinez Y. V., Perez Alonso V., Ayer Miller V., Gandemer V., Lotero V., Mishkova V., Gomez-Garcia W., Margaryan Y., and Syed Y.

Abstract

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count

Published
2021

2. Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Author

Sheena Mukkada, Nickhill Bhakta, Guillermo L Chantada, Yichen Chen, Yuvanesh Vedaraju, Lane Faughnan, Maysam R Homsi, Hilmarie Muniz-Talavera, Radhikesh Ranadive, Monika Metzger, Paola Friedrich, Asya Agulnik, Sima Jeha, Catherine Lam, Rashmi Dalvi, Laila Hessissen, Daniel C Moreira, Victor M Santana, Michael Sullivan, Eric Bouffet, Miguela A Caniza, Meenakshi Devidas, Kathy Pritchard-Jones, Carlos Rodriguez-Galindo, A Juan Ribelles, Adriana Balduzzi, Alaa Elhaddad, Alejandra Casanovas, Alejandra Garcia Velazquez, Aliaksandra Laptsevich, Alicia Chang, Alessandra Lamenha F. Sampaio, Almudena González Prieto, Alvaro Lassaletta, Amaranto Suarez M, Ana Patricia Alcasabas, Anca Colita, Andres Morales La Madrid, Angélica Samudio, Annalisa Tondo, Antonella Colombini, Antonis Kattamis, N Araceli Lopez Facundo, Arpita Bhattacharyya, Aurélia Alimi, Aurélie Phulpin, Barbora Vakrmanova, Basak A Aksoy, Benoit Brethon, Jator Brian Kobuin, Carla Nolasco Monteiro, Catherine Paillard, Catherine Vezina, Bozkurt Ceyhun, Cristiana Hentea, Cristina Meazza, Daniel Ortiz-Morales, Roque Daniel Solorzano, Daniela Arce Cabrera, Daniele Zama, Debjani Ghosh, Diana Ramírez-Rivera, Doris A Calle Jara, Dragana Janic, Elianneth Rey Helo, Elodie Gouache, Enmanuel Guerrero Quiroz, Enrique Lopez, Eric Thebault, Essy Maradiegue, Eva de Berranger, Fatma S E Ebeid, Federica Galaverna, Federico Antillon-Klussmann, Felipe Espinoza Chacur, Fernando Daniel Negro, Francesca Carraro, Francesca Compagno, Francisco Barriga, Gabriela Tamayo Pedraza, Gissela Sanchez Fernandez, Gita Naidu, Gülnur Tokuc, Hamidah Alias, Hannah Grace B Segocio, Houda Boudiaf, Imelda Asetre Luna, Iris Maia, Itziar Astigarraga, Ivan Maza, Jacqueline E Montoya Vásquez, Janez Jazbec, Jelena Lazic, Jeniffer Beck Dean, Jeremie Rouger-Gaudichon, Johanny Carolina Contreras González, Jorge Huerta Aragonés, José L Fuster, Juan Quintana, Julia Palma, Karel Svojgr, Karina Quintero, Karolina Malic Tudor, Kleopatra Georgantzi, Kris Ann P Schultz, Laura Ureña Horno, Lidia Fraquelli, Linda Meneghello, Lobna Shalaby, Lola L Macias Mora, Lorna A Renner, Luciana Nunes Silva, Luisa Sisinni, Mahmoud Hammad, M Fernández Sanmartín, C Marcela Zubieta A, María Constanza Drozdowski, Maria Kourti, Marcela María Palladino, Maria R Miranda Madrazo, Marilyne Poiree, Marina Popova, Mario Melgar, Marta Baragaño, Martha J Avilés-Robles, Massimo Provenzi, Mecneide Mendes Lins, Mehmet Fatih Orhan, Milena Villarroel, Mónica Jerónimo, Mónica Varas Palma, Muhammad Rafie Raza, Mulindwa M Justin, Najma Shaheen, Nerea Domínguez-Pinilla, Nicholas S Whipple, Nicolas André, Ondrej Hrusak, Pablo Velasco Puyó, Pamela Zacasa Vargas, Paola Olate Mellado, Pascale Yola Gassant, Paulina Diaz Romero, Raffaella De Santis, Rejin Kebudi, Riza Boranbayeva, Roberto Vasquez, Romel A. Segura, Roy Enrique Rosado, Sandra Gómez, Sandra Raimbault, Sanjeeva Gunasekera, Sara M Makkeyah, Sema Buyukkapu Bay, Sergio M Gómez, Séverine Bouttefroy, Shahnoor Islam, Sherif Abouelnaga, Silvio Fabio Torres, Simone Cesaro, Sofia Nunes, Soraia Rouxinol, Sucharita Bhaumik, Symbat Saliyeva, Tamara Inostroza, Thelma Velasquez, Tint Myo Hnin, Ulrika Norén-Nyström, Valentina Baretta, Yajaira Valentine Jimenez-Antolinez, Vanesa Pérez Alonso, Vanessa Ayer Miller, Virginie Gandemer, Viviana Lotero, Volha Mishkova, Wendy Gómez-García, Yeva Margaryan, Yumna Syed, Mukkada S., Bhakta N., Chantada G.L., Chen Y., Vedaraju Y., Faughnan L., Homsi M.R., Muniz-Talavera H., Ranadive R., Metzger M., Friedrich P., Agulnik A., Jeha S., Lam C., Dalvi R., Hessissen L., Moreira D.C., Santana V.M., Sullivan M., Bouffet E., Caniza M.A., Devidas M., Pritchard-Jones K., Rodriguez-Galindo C., Ribelles A.J., Balduzzi A., Elhaddad A., Casanovas A., Garcia Velazquez A., Laptsevich A., Chang A., F. Sampaio A.L., Gonzalez Prieto A., Lassaletta A., Suarez M A., Alcasabas A.P., Colita A., Morales La Madrid A., Samudio A., Tondo A., Colombini A., Kattamis A., Lopez Facundo N.A., Bhattacharyya A., Alimi A., Phulpin A., Vakrmanova B., Aksoy B.A., Brethon B., Kobuin J.B., Nolasco Monteiro C., Paillard C., Vezina C., Ceyhun B., Hentea C., Meazza C., Ortiz-Morales D., Solorzano R.D., Arce Cabrera D., Zama D., Ghosh D., Ramirez-Rivera D., Calle Jara D.A., Janic D., Rey Helo E., Gouache E., Guerrero Quiroz E., Lopez E., Thebault E., Maradiegue E., de Berranger E., Ebeid F.S.E., Galaverna F., Antillon-Klussmann F., Espinoza Chacur F., Negro F.D., Carraro F., Compagno F., Barriga F., Tamayo Pedraza G., Sanchez Fernandez G., Naidu G., Tokuc G., Alias H., B Segocio H.G., Boudiaf H., Asetre Luna I., Maia I., Astigarraga I., Maza I., Montoya Vasquez J.E., Jazbec J., Lazic J., Beck Dean J., Rouger-Gaudichon J., Contreras Gonzalez J.C., Huerta Aragones J., Fuster J.L., Quintana J., Palma J., Svojgr K., Quintero K., Malic Tudor K., Georgantzi K., P Schultz K.A., Urena Horno L., Fraquelli L., Meneghello L., Shalaby L., Macias Mora L.L., A Renner L., Nunes Silva L., Sisinni L., Hammad M., Fernandez Sanmartin M., Zubieta A C.M., Drozdowski M.C., Kourti M., Palladino M.M., Miranda Madrazo M.R., Poiree M., Popova M., Melgar M., Baragano M., Aviles-Robles M.J., Provenzi M., Mendes Lins M., Fatih Orhan M., Villarroel M., Jeronimo M., Varas Palma M., Rafie Raza M., M Justin M., Shaheen N., Dominguez-Pinilla N., Whipple N.S., Andre N., Hrusak O., Velasco Puyo P., Zacasa Vargas P., Olate Mellado P., Yola Gassant P., Diaz Romero P., De Santis R., Kebudi R., Boranbayeva R., Vasquez R., Segura R.A., Rosado R.E., Gomez S., Raimbault S., Gunasekera S., Makkeyah S.M., Buyukkapu Bay S., M Gomez S., Bouttefroy S., Islam S., Abouelnaga S., Torres S.F., Cesaro S., Nunes S., Rouxinol S., Bhaumik S., Saliyeva S., Inostroza T., Velasquez T., Hnin T.M., Noren-Nystrom U., Baretta V., Jimenez-Antolinez Y.V., Perez Alonso V., Ayer Miller V., Gandemer V., Lotero V., Mishkova V., Gomez-Garcia W., Margaryan Y., Syed Y., Mukkada, S, Bhakta, N, Chantada, G, Chen, Y, Vedaraju, Y, Faughnan, L, Homsi, M, Muniz-Talavera, H, Ranadive, R, Metzger, M, Friedrich, P, Agulnik, A, Jeha, S, Lam, C, Dalvi, R, Hessissen, L, Moreira, D, Santana, V, Sullivan, M, Bouffet, E, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Ribelles, A, Balduzzi, A, Elhaddad, A, Casanovas, A, Garcia Velazquez, A, Laptsevich, A, Chang, A, F. Sampaio A., L, Gonzalez Prieto, A, Lassaletta, A, Suarez M, A, Alcasabas, A, Colita, A, Morales La Madrid, A, Samudio, A, Tondo, A, Colombini, A, Kattamis, A, Lopez Facundo, N, Bhattacharyya, A, Alimi, A, Phulpin, A, Vakrmanova, B, Aksoy, B, Brethon, B, Kobuin, J, Nolasco Monteiro, C, Paillard, C, Vezina, C, Ceyhun, B, Hentea, C, Meazza, C, Ortiz-Morales, D, Solorzano, R, Arce Cabrera, D, Zama, D, Ghosh, D, Ramirez-Rivera, D, Calle Jara, D, Janic, D, Rey Helo, E, Gouache, E, Guerrero Quiroz, E, Lopez, E, Thebault, E, Maradiegue, E, de Berranger, E, Ebeid, F, Galaverna, F, Antillon-Klussmann, F, Espinoza Chacur, F, Negro, F, Carraro, F, Compagno, F, Barriga, F, Tamayo Pedraza, G, Sanchez Fernandez, G, Naidu, G, Tokuc, G, Alias, H, B Segocio, H, Boudiaf, H, Asetre Luna, I, Maia, I, Astigarraga, I, Maza, I, Montoya Vasquez, J, Jazbec, J, Lazic, J, Beck Dean, J, Rouger-Gaudichon, J, Contreras Gonzalez, J, Huerta Aragones, J, Fuster, J, Quintana, J, Palma, J, Svojgr, K, Quintero, K, Malic Tudor, K, Georgantzi, K, P Schultz, K, Urena Horno, L, Fraquelli, L, Meneghello, L, Shalaby, L, Macias Mora, L, A Renner, L, Nunes Silva, L, Sisinni, L, Hammad, M, Fernandez Sanmartin, M, Zubieta A, C, Drozdowski, M, Kourti, M, Palladino, M, Miranda Madrazo, M, Poiree, M, Popova, M, Melgar, M, Baragano, M, Aviles-Robles, M, Provenzi, M, Mendes Lins, M, Fatih Orhan, M, Villarroel, M, Jeronimo, M, Varas Palma, M, Rafie Raza, M, M Justin, M, Shaheen, N, Dominguez-Pinilla, N, Whipple, N, Andre, N, Hrusak, O, Velasco Puyo, P, Zacasa Vargas, P, Olate Mellado, P, Yola Gassant, P, Diaz Romero, P, De Santis, R, Kebudi, R, Boranbayeva, R, Vasquez, R, Segura, R, Rosado, R, Gomez, S, Raimbault, S, Gunasekera, S, Makkeyah, S, Buyukkapu Bay, S, M Gomez, S, Bouttefroy, S, Islam, S, Abouelnaga, S, Torres, S, Cesaro, S, Nunes, S, Rouxinol, S, Bhaumik, S, Saliyeva, S, Inostroza, T, Velasquez, T, Hnin, T, Noren-Nystrom, U, Baretta, V, Jimenez-Antolinez, Y, Perez Alonso, V, Ayer Miller, V, Gandemer, V, Lotero, V, Mishkova, V, Gomez-Garcia, W, Margaryan, Y, and Syed, Y

Subjects
Male, Pediatrics, medicine.medical_specialty, COVID-19, Children, adolescents, cancer, Adolescent, MEDLINE, Severity of Illness Index, Health systems, Neoplasms, purl.org/becyt/ford/3.2 [https], Severity of illness, medicine, Humans, Child, Children, Pandemics, Pandemic, business.industry, SARS-CoV-2, Risk Factor, Infant, Newborn, Infant, Cancer, COVID-19, Odds ratio, Articles, medicine.disease, Transplantation, Oncology, Child, Preschool, Cohort, Absolute neutrophil count, Neoplasm, purl.org/becyt/ford/3 [https], Female, Cohort Studie, business, Delivery of Health Care, Human, Cohort study
Abstract

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (

Published
2021

3. Somatic RAP1B gain-of-function variant underlies isolated thrombocytopenia and immunodeficiency.

Author

Benavides-Nieto M, Adam F, Martin E, Boussard C, Lagresle-Peyrou C, Callebaut I, Kauskot A, Repérant C, Feng M, Bordet JC, Castelle M, Morelle G, Brouzes C, Zarhrate M, Panikulam P, Lambert N, Picard C, Bodet D, Rouger-Gaudichon J, Revy P, de Villartay JP, and Moshous D

Subjects
Humans, Male, Amino Acid Substitution, Hematopoietic Stem Cell Transplantation, Immunologic Deficiency Syndromes genetics, Mutation, Missense, Infant, Newborn, Infant, Child, Preschool, Child, Gain of Function Mutation, rap GTP-Binding Proteins genetics, rap GTP-Binding Proteins metabolism, Thrombocytopenia genetics, Thrombocytopenia pathology
Abstract

The ubiquitously expressed small GTPase Ras-related protein 1B (RAP1B) acts as a molecular switch that regulates cell signaling, cytoskeletal remodeling, and cell trafficking and activates integrins in platelets and lymphocytes. The residue G12 in the P-loop is required for the RAP1B-GTPase conformational switch. Heterozygous germline RAP1B variants have been described in patients with syndromic thrombocytopenia. However, the causality and pathophysiological impact remained unexplored. We report a boy with neonatal thrombocytopenia, combined immunodeficiency, neutropenia, and monocytopenia caused by a heterozygous de novo single nucleotide substitution, c.35G>A (p.G12E) in RAP1B. We demonstrate that G12E and the previously described G12V and G60R were gain-of-function variants that increased RAP1B activation, talin recruitment, and integrin activation, thereby modifying late responses such as platelet activation, T cell proliferation, and migration. We show that in our patient, G12E was a somatic variant whose allele frequency decreased over time in the peripheral immune compartment, but remained stable in bone marrow cells, suggesting a differential effect in distinct cell populations. Allogeneic hematopoietic stem cell transplantation fully restored the patient's hemato-immunological phenotype. Our findings define monoallelic RAP1B gain-of-function variants as a cause for constitutive immunodeficiency and thrombocytopenia. The phenotypic spectrum ranged from isolated hematological manifestations in our patient with somatic mosaicism to complex syndromic features in patients with reported germline RAP1B variants.

Published
2024
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4. Hypoxia regulates CD9 expression and dissemination of B lymphoblasts.

Author

Rouger-Gaudichon J, Cousin E, Jakobczyk H, Debaize L, Rio AG, Forestier A, Arnaud MP, Villacreces A, Praloran V, Jacamo R, Galibert MD, Troadec MB, and Gandemer V

Subjects
Male, Humans, Mice, Animals, Tetraspanin 29 genetics, Tetraspanin 29 metabolism, Cell Adhesion, Oxygen, Signal Transduction, Hypoxia
Abstract

Acute lymphoblastic leukemias (ALL) are the most frequent cancer in children and derive most often from B-cell precursors. Current survival rates roughly reach 90% at 10 years from diagnosis. However, 15-20% of children still relapse with a significant risk of death. Our previous work showed that the transmembrane protein CD9 plays a major role in lymphoblasts migration into sanctuary sites, especially in testis, through the activation of RAC1 signaling upon blasts stimulation with C-X-C chemokine ligand 12 (CXCL12). Here, we identified common factors shared by the bone marrow and extramedullary niches which could upregulate CD9 expression and function. We found that low oxygen levels enhance CD9 expression both at mRNA and protein levels. We further determined that Hypoxia Inducible Factor 1α (HIF1α), the master transcription factor involved in hypoxia response, binds directly CD9 promoter and induce CD9 transcription. We also showed that CD9 protein is crucial for leukemic cell adhesion and migration at low oxygen levels, possibly through its action on RAC1 signaling. Mouse xenograft experiments indicate that HIF1α signaling pathway promotes ALL cells engraftment in a CD9-dependent manner. The present work increments our understanding of CD9 implication in ALL pathogenesis., Competing Interests: Conflict of interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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5. ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis.

Author

Jakobczyk H, Jiang Y, Debaize L, Soubise B, Avner S, Sérandour AA, Rouger-Gaudichon J, Rio AG, Carroll JS, Raslova H, Gilot D, Liu Z, Demengeot J, Salbert G, Douet-Guilbert N, Corcos L, Galibert MD, Gandemer V, and Troadec MB

Subjects
Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Core Binding Factor Alpha 2 Subunit genetics, Homeodomain Proteins genetics, Humans, Oncogene Proteins, Fusion genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Tumor Cells, Cultured, Cell Transformation, Neoplastic pathology, Core Binding Factor Alpha 2 Subunit metabolism, Gene Expression Regulation, Leukemic, Homeodomain Proteins metabolism, Oncogene Proteins, Fusion metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology
Published
2022
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6. Invasive Fungal Infections in Immunocompromised Children: Novel Insight Following a National Study.

Author

Olivier-Gougenheim L, Rama N, Dupont D, Saultier P, Leverger G, AbouChahla W, Paillard C, Gandemer V, Theron A, Freycon C, Pluchart C, Blouin P, Pellier I, Thouvenin-Doulet S, Desplantes C, Ducassou S, Oudot C, Rouger-Gaudichon J, Cheikh N, Poiree M, Schneider P, Plat G, Contet A, Rialland F, Gouache E, Brethon B, Bertrand Y, and Domenech C

Subjects
Adolescent, Child, Child, Preschool, Female, France, Humans, Incidence, Infant, Infant, Newborn, Invasive Fungal Infections diagnosis, Invasive Fungal Infections therapy, Male, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Immunocompromised Host, Invasive Fungal Infections epidemiology, Leukemia, Myeloid, Acute immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology
Abstract

Objective: To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT)., Study Design: We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units., Results: From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with "emergent" fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P < .0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P = 4.90 ×10 -4 ) compared with a-HSCT recipients who did not receive antifungal prophylaxis. The main cause of IFI in children receiving prophylaxis was emergent pathogens (41%), such as mucormycosis and fusariosis, which were resistant to the prophylactic agents., Conclusions: The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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7. COVID19 and acute lymphoblastic leukemias of children and adolescents: Updated recommendations (Version 2) of the Leukemia Committee of the French Society for the fight against Cancers and leukemias in children and adolescents (SFCE).

Author

Rouger-Gaudichon J, Bertrand Y, Boissel N, Brethon B, Ducassou S, Gandemer V, Halfon-Domenech C, Leblanc T, Leverger G, Michel G, Petit A, Ray-Lunven AF, Rohrlich PS, Schneider P, Sirvent N, Strullu M, and Baruchel A

Subjects
Adenosine Monophosphate analogs & derivatives, Adenosine Monophosphate therapeutic use, Adolescent, Adrenal Cortex Hormones therapeutic use, Alanine analogs & derivatives, Alanine therapeutic use, Antiviral Agents therapeutic use, COVID-19 diagnosis, COVID-19 Nucleic Acid Testing, COVID-19 Vaccines therapeutic use, Cancer Care Facilities, Child, Consolidation Chemotherapy, Drug Interactions, France epidemiology, Humans, Induction Chemotherapy methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Maintenance Chemotherapy methods, Recurrence, Risk Assessment, Societies, Medical, COVID-19 Drug Treatment, COVID-19 epidemiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
Abstract

Since the emergence of the SARS-CoV-2 infection, many recommendations have been made. However, the very specific nature of acute lymphoblastic leukemias and their treatment in children and adolescents led the Leukemia Committee of the French Society for the fight against Cancers and leukemias in children and adolescents (SFCE) to propose more specific recommendations. Here is the second version of these recommendations updated according to the evolution of knowledge on COVID19., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Published
2021
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8. Reduction of RUNX1 transcription factor activity by a CBFA2T3-mimicking peptide: application to B cell precursor acute lymphoblastic leukemia.

Author

Jakobczyk H, Debaize L, Soubise B, Avner S, Rouger-Gaudichon J, Commet S, Jiang Y, Sérandour AA, Rio AG, Carroll JS, Wichmann C, Lie-A-Ling M, Lacaud G, Corcos L, Salbert G, Galibert MD, Gandemer V, and Troadec MB

Subjects
Antineoplastic Agents chemistry, Cell Line, Tumor, Child, Core Binding Factor Alpha 2 Subunit genetics, Core Binding Factor Alpha 2 Subunit metabolism, Gene Expression Regulation, Leukemic drug effects, Humans, Peptides chemistry, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Protein Interaction Domains and Motifs drug effects, Repressor Proteins chemistry, Repressor Proteins genetics, Transcriptional Activation drug effects, Antineoplastic Agents pharmacology, Core Binding Factor Alpha 2 Subunit antagonists & inhibitors, Peptides pharmacology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Protein Interaction Maps drug effects, Repressor Proteins metabolism
Abstract

Background: B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer. Identifying key players involved in proliferation of BCP-ALL cells is crucial to propose new therapeutic targets. Runt Related Transcription Factor 1 (RUNX1) and Core-Binding Factor Runt Domain Alpha Subunit 2 Translocated To 3 (CBFA2T3, ETO2, MTG16) are master regulators of hematopoiesis and are implicated in leukemia., Methods: We worked with BCP-ALL mononuclear bone marrow patients' cells and BCP-ALL cell lines, and performed Chromatin Immunoprecipitations followed by Sequencing (ChIP-Seq), co-immunoprecipitations (co-IP), proximity ligation assays (PLA), luciferase reporter assays and mouse xenograft models., Results: We demonstrated that CBFA2T3 transcript levels correlate with RUNX1 expression in the pediatric t(12;21) ETV6-RUNX1 BCP-ALL. By ChIP-Seq in BCP-ALL patients' cells and cell lines, we found that RUNX1 is recruited on its promoter and on an enhancer of CBFA2T3 located - 2 kb upstream CBFA2T3 promoter and that, subsequently, the transcription factor RUNX1 drives both RUNX1 and CBFA2T3 expression. We demonstrated that, mechanistically, RUNX1 and CBFA2T3 can be part of the same complex allowing CBFA2T3 to strongly potentiate the activity of the transcription factor RUNX1. Finally, we characterized a CBFA2T3-mimicking peptide that inhibits the interaction between RUNX1 and CBFA2T3, abrogating the activity of this transcription complex and reducing BCP-ALL lymphoblast proliferation., Conclusions: Altogether, our findings reveal a novel and important activation loop between the transcription regulator CBFA2T3 and the transcription factor RUNX1 that promotes BCP-ALL proliferation, supporting the development of an innovative therapeutic approach based on the NHR2 subdomain of CBFA2T3 protein.

Published
2021
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9. Impact of COVID-19 on cancer care: A survey from the French Society of Pediatric Oncology (SFCE).

Author

Rouger-Gaudichon J, Gariazzo L, Thébault E, Brethon B, Fenwarth L, Gambart M, Alimi A, Réguerre Y, Piguet C, Jubert C, Gouache E, Thébaud E, Plantaz D, Paillard C, Raimbault S, Haouy S, Schneider P, Phulpin A, Mallebranche C, Dubrasquet M, de Berranger E, Devoldere C, Laithier V, Poirée M, Thouvenin S, Carausu L, Dupraz C, Bouttefroy S, André N, and Gandemer V

Subjects
Adolescent, Child, Child, Preschool, Female, France epidemiology, Humans, Infant, Male, Medical Oncology, Pediatrics, Practice Guidelines as Topic, Societies, Medical, COVID-19 epidemiology, COVID-19 therapy, Delivery of Health Care, Neoplasms epidemiology, Neoplasms therapy, SARS-CoV-2
Published
2021
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10. Impact of the First Wave of COVID-19 on Pediatric Oncology and Hematology: A Report from the French Society of Pediatric Oncology.

Author

Rouger-Gaudichon J, Thébault E, Félix A, Phulpin A, Paillard C, Alimi A, Brethon B, Gouache E, Raimbault S, de Berranger E, Poirée M, Bouttefroy S, André N, Gandemer V, and On Behalf Of Société Française de Lutte Contre Les Cancers Et Leucémies de l'Enfant Et de L'adolescent Sfce

Abstract

Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 in patients followed in French pediatric oncology and hematology wards. All patients diagnosed with COVID-19 and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Data were available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Children and young adults treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored.

Published
2020
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11. COVID-19 in pediatric oncology from French pediatric oncology and hematology centers: High risk of severe forms?

Author

André N, Rouger-Gaudichon J, Brethon B, Phulpin A, Thébault É, Pertuisel S, and Gandemer V

Subjects
Adolescent, Anemia, Sickle Cell therapy, Betacoronavirus, COVID-19, Child, Child, Preschool, Female, France, Hematology, Hematopoietic Stem Cell Transplantation, Humans, Immunocompromised Host, Intensive Care Units, Leukemia, B-Cell drug therapy, Leukemia, B-Cell virology, Male, Medical Oncology, Pandemics, Pediatrics, Risk Factors, SARS-CoV-2, Young Adult, Anemia, Sickle Cell complications, Coronavirus Infections epidemiology, Leukemia, B-Cell complications, Pneumonia, Viral epidemiology
Published
2020
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