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1. Automated identification of leukocyte subsets improves standardization of database-guided expert-supervised diagnostic orientation in acute leukemia: a EuroFlow study

Author

Lhermitte, Ludovic, Barreau, Sylvain, Morf, Daniela, Fernandez, Paula, Grigore, Georgiana, Barrena, Susana, de Bie, Maaike, Flores-Montero, Juan, Brüggemann, Monika, Mejstrikova, Ester, Nierkens, Stefan, Burgos, Leire, Caetano, Joana, Gaipa, Giuseppe, Buracchi, Chiara, da Costa, Elaine Sobral, Sedek, Lukasz, Szczepański, Tomasz, Aanei, Carmen-Mariana, van der Sluijs-Gelling, Alita, Delgado, Alejandro Hernández, Fluxa, Rafael, Lecrevisse, Quentin, Pedreira, Carlos E., van Dongen, Jacques J.M., Orfao, Alberto, van der Velden, Vincent H.J., van Dongen, J. J.M., Bitter, W.M., Lubbers, B.R., Teodosio, C.I., Zlei, M., van der Sluijs-Gelling, A.J., de Bie, F., de Bruin-Versteeg, S., van der Burg, M., Schilham, M.W., van der Velden, V. H.J., Langerak, A.W., te Marvelde, J., Bras, A.E., Schilperoord-Vermeulen, J., Jugooa, R., Heezen, K.C., Orfao, A., Almeida, J., Vidriales, M.B., Flores-Montero, J., Pérez-Andrés, M., Matarraz, S., Martín, L., Lecrevisse, Q., Pérez-Morán, J.J., Puig, N., Almeida, A. Medina, Gomes da Silva, M., Faria, T., Brüggemann, M., Ritgen, M., Szczepanowski, M., Kohlscheen, S., Laqua, A., Harbst, E., Finke, J., Asnafi, V., Lhermitte, L., Duroyon, E., Trka, J., Hrusak, O., Kalina, T., Mejstrikova, E., Novakova, M., Thurner, D., Kanderova, V., Szczepanski, T., Sędek, L., Bulsa, J., Slota, L., Kulis, J., Pedreira, C.E., da Costa, E. Sobral, Nierkens, S., de Jong, A., de Koning, A., Lima, M., Santos, A.H., Böttcher, S., Lange, S., Engelmann, R., Paape, D., Machka, C., Gaipa, G., Burracchi, C., Bugarin, C., Lopez-Granados, E., del Pino Molina, L., Campos-Guyotat, L., Aanei, C., Miguel, J. F. San, Paiva, B., Burgos, L., Villamor-Casas, N., Magnano, L., Philippé, J., Bonroy, C., Denys, B., Willems, A., Breughe, P., de Wolf, J., Sousa, A.E., Silva, S.L., Fernandez, P., and Morf, D.

Published
2021
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2. Improved survival and MRD remission with blinatumomab vs. chemotherapy in children with first high-risk relapse B-ALL

Author

Locatelli, F, Zugmaier, G, Rizzari, C, Morris, J, Gruhn, B, Klingebiel, T, Parasole, R, Linderkamp, C, Flotho, C, Petit, A, Micalizzi, C, Zeng, Y, Desai, R, Kormany, W, Eckert, C, Moricke, A, Sartor, M, Hrusak, O, Peters, C, Saha, V, Vinti, L, von Stackelberg, A, Locatelli F., Zugmaier G., Rizzari C., Morris J. D., Gruhn B., Klingebiel T., Parasole R., Linderkamp C., Flotho C., Petit A., Micalizzi C., Zeng Y., Desai R., Kormany W. N., Eckert C., Moricke A., Sartor M., Hrusak O., Peters C., Saha V., Vinti L., von Stackelberg A., Locatelli, F, Zugmaier, G, Rizzari, C, Morris, J, Gruhn, B, Klingebiel, T, Parasole, R, Linderkamp, C, Flotho, C, Petit, A, Micalizzi, C, Zeng, Y, Desai, R, Kormany, W, Eckert, C, Moricke, A, Sartor, M, Hrusak, O, Peters, C, Saha, V, Vinti, L, von Stackelberg, A, Locatelli F., Zugmaier G., Rizzari C., Morris J. D., Gruhn B., Klingebiel T., Parasole R., Linderkamp C., Flotho C., Petit A., Micalizzi C., Zeng Y., Desai R., Kormany W. N., Eckert C., Moricke A., Sartor M., Hrusak O., Peters C., Saha V., Vinti L., and von Stackelberg A.

Published
2023

4. Improved survival and MRD remission with blinatumomab vs. chemotherapy in children with first high-risk relapse B-ALL

Author

Locatelli, Franco, Zugmaier, G., Rizzari, C., Morris, J. D., Gruhn, B., Klingebiel, T., Parasole, R., Linderkamp, C., Flotho, C., Petit, A., Micalizzi, C., Zeng, Y., Desai, R., Kormany, W. N., Eckert, C., Moricke, A., Sartor, M., Hrusak, O., Peters, C., Saha, V., Vinti, L., von Stackelberg, A., Locatelli F. (ORCID:0000-0002-7976-3654), Locatelli, Franco, Zugmaier, G., Rizzari, C., Morris, J. D., Gruhn, B., Klingebiel, T., Parasole, R., Linderkamp, C., Flotho, C., Petit, A., Micalizzi, C., Zeng, Y., Desai, R., Kormany, W. N., Eckert, C., Moricke, A., Sartor, M., Hrusak, O., Peters, C., Saha, V., Vinti, L., von Stackelberg, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2023

5. Automated identification of leukocyte subsets improves standardization of database-guided expert-supervised diagnostic orientation in acute leukemia: a EuroFlow study

Author

Lhermitte, L, Barreau, S, Morf, D, Fernandez, P, Grigore, G, Barrena, S, de Bie, M, Flores-Montero, J, Bruggemann, M, Mejstrikova, E, Nierkens, S, Burgos, L, Caetano, J, Gaipa, G, Buracchi, C, da Costa, E, Sedek, L, Szczepanski, T, Aanei, C, van der Sluijs-Gelling, A, Delgado, A, Fluxa, R, Lecrevisse, Q, Pedreira, C, van Dongen, J, Orfao, A, van der Velden, V, Bitter, W, Lubbers, B, Teodosio, C, Zlei, M, de Bie, F, de Bruin-Versteeg, S, van der Burg, M, Schilham, M, Langerak, A, te Marvelde, J, Bras, A, Schilperoord-Vermeulen, J, Jugooa, R, Heezen, K, Almeida, J, Vidriales, M, Perez-Andres, M, Matarraz, S, Martin, L, Perez-Moran, J, Puig, N, Almeida, A, Gomes da Silva, M, Faria, T, Ritgen, M, Szczepanowski, M, Kohlscheen, S, Laqua, A, Harbst, E, Finke, J, Asnafi, V, Duroyon, E, Trka, J, Hrusak, O, Kalina, T, Novakova, M, Thurner, D, Kanderova, V, Bulsa, J, Slota, L, Kulis, J, de Jong, A, de Koning, A, Lima, M, Santos, A, Bottcher, S, Lange, S, Engelmann, R, Paape, D, Machka, C, Burracchi, C, Bugarin, C, Lopez-Granados, E, del Pino Molina, L, Campos-Guyotat, L, Miguel, J, Paiva, B, Villamor-Casas, N, Magnano, L, Philippe, J, Bonroy, C, Denys, B, Willems, A, Breughe, P, de Wolf, J, Sousa, A, Silva, S, Lhermitte L., Barreau S., Morf D., Fernandez P., Grigore G., Barrena S., de Bie M., Flores-Montero J., Bruggemann M., Mejstrikova E., Nierkens S., Burgos L., Caetano J., Gaipa G., Buracchi C., da Costa E. S., Sedek L., Szczepanski T., Aanei C. -M., van der Sluijs-Gelling A., Delgado A. H., Fluxa R., Lecrevisse Q., Pedreira C. E., van Dongen J. J. M., Orfao A., van der Velden V. H. J., Bitter W. M., Lubbers B. R., Teodosio C. I., Zlei M., van der Sluijs-Gelling A. J., de Bie F., de Bruin-Versteeg S., van der Burg M., Schilham M. W., Langerak A. W., te Marvelde J., Bras A. E., Schilperoord-Vermeulen J., Jugooa R., Heezen K. C., Almeida J., Vidriales M. B., Perez-Andres M., Matarraz S., Martin L., Perez-Moran J. J., Puig N., Almeida A. M., Gomes da Silva M., Faria T., Ritgen M., Szczepanowski M., Kohlscheen S., Laqua A., Harbst E., Finke J., Asnafi V., Duroyon E., Trka J., Hrusak O., Kalina T., Novakova M., Thurner D., Kanderova V., Bulsa J., Slota L., Kulis J., de Jong A., de Koning A., Lima M., Santos A. H., Bottcher S., Lange S., Engelmann R., Paape D., Machka C., Burracchi C., Bugarin C., Lopez-Granados E., del Pino Molina L., Campos-Guyotat L., Aanei C., Miguel J. F. S., Paiva B., Villamor-Casas N., Magnano L., Philippe J., Bonroy C., Denys B., Willems A., Breughe P., de Wolf J., Sousa A. E., Silva S. L., Lhermitte, L, Barreau, S, Morf, D, Fernandez, P, Grigore, G, Barrena, S, de Bie, M, Flores-Montero, J, Bruggemann, M, Mejstrikova, E, Nierkens, S, Burgos, L, Caetano, J, Gaipa, G, Buracchi, C, da Costa, E, Sedek, L, Szczepanski, T, Aanei, C, van der Sluijs-Gelling, A, Delgado, A, Fluxa, R, Lecrevisse, Q, Pedreira, C, van Dongen, J, Orfao, A, van der Velden, V, Bitter, W, Lubbers, B, Teodosio, C, Zlei, M, de Bie, F, de Bruin-Versteeg, S, van der Burg, M, Schilham, M, Langerak, A, te Marvelde, J, Bras, A, Schilperoord-Vermeulen, J, Jugooa, R, Heezen, K, Almeida, J, Vidriales, M, Perez-Andres, M, Matarraz, S, Martin, L, Perez-Moran, J, Puig, N, Almeida, A, Gomes da Silva, M, Faria, T, Ritgen, M, Szczepanowski, M, Kohlscheen, S, Laqua, A, Harbst, E, Finke, J, Asnafi, V, Duroyon, E, Trka, J, Hrusak, O, Kalina, T, Novakova, M, Thurner, D, Kanderova, V, Bulsa, J, Slota, L, Kulis, J, de Jong, A, de Koning, A, Lima, M, Santos, A, Bottcher, S, Lange, S, Engelmann, R, Paape, D, Machka, C, Burracchi, C, Bugarin, C, Lopez-Granados, E, del Pino Molina, L, Campos-Guyotat, L, Miguel, J, Paiva, B, Villamor-Casas, N, Magnano, L, Philippe, J, Bonroy, C, Denys, B, Willems, A, Breughe, P, de Wolf, J, Sousa, A, Silva, S, Lhermitte L., Barreau S., Morf D., Fernandez P., Grigore G., Barrena S., de Bie M., Flores-Montero J., Bruggemann M., Mejstrikova E., Nierkens S., Burgos L., Caetano J., Gaipa G., Buracchi C., da Costa E. S., Sedek L., Szczepanski T., Aanei C. -M., van der Sluijs-Gelling A., Delgado A. H., Fluxa R., Lecrevisse Q., Pedreira C. E., van Dongen J. J. M., Orfao A., van der Velden V. H. J., Bitter W. M., Lubbers B. R., Teodosio C. I., Zlei M., van der Sluijs-Gelling A. J., de Bie F., de Bruin-Versteeg S., van der Burg M., Schilham M. W., Langerak A. W., te Marvelde J., Bras A. E., Schilperoord-Vermeulen J., Jugooa R., Heezen K. C., Almeida J., Vidriales M. B., Perez-Andres M., Matarraz S., Martin L., Perez-Moran J. J., Puig N., Almeida A. M., Gomes da Silva M., Faria T., Ritgen M., Szczepanowski M., Kohlscheen S., Laqua A., Harbst E., Finke J., Asnafi V., Duroyon E., Trka J., Hrusak O., Kalina T., Novakova M., Thurner D., Kanderova V., Bulsa J., Slota L., Kulis J., de Jong A., de Koning A., Lima M., Santos A. H., Bottcher S., Lange S., Engelmann R., Paape D., Machka C., Burracchi C., Bugarin C., Lopez-Granados E., del Pino Molina L., Campos-Guyotat L., Aanei C., Miguel J. F. S., Paiva B., Villamor-Casas N., Magnano L., Philippe J., Bonroy C., Denys B., Willems A., Breughe P., de Wolf J., Sousa A. E., and Silva S. L.

Abstract

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide toward the relevant classification panel and final diagnosis. In this study, we designed and validated an algorithm for automated (database-supported) gating and identification (AGI tool) of cell subsets within samples stained with ALOT. A reference database of normal peripheral blood (PB, n = 41) and bone marrow (BM; n = 45) samples analyzed with the ALOT was constructed, and served as a reference for the AGI tool to automatically identify normal cells. Populations not unequivocally identified as normal cells were labeled as checks and were classified by an expert. Additional normal BM (n = 25) and PB (n = 43) and leukemic samples (n = 109), analyzed in parallel by experts and the AGI tool, were used to evaluate the AGI tool. Analysis of normal PB and BM samples showed low percentages of checks (<3% in PB, <10% in BM), with variations between different laboratories. Manual analysis and AGI analysis of normal and leukemic samples showed high levels of correlation between cell numbers (r2 > 0.95 for all cell types in PB and r2 > 0.75 in BM) and resulted in highly concordant classification of leukemic cells by our previously published automated database-guided expert-supervised orientation tool for immunophenotypic diagnosis and classification of acute leukemia (Compass tool). Similar data were obtained using alternative, commercially available tubes, confirming the robustness of the developed tools. The AGI tool represents an innovative step in minimizing human intervention and requirements in expertise, toward a “sample-in and result-out” approach which may result in more objective and reproducible data analysis and diagnostics. The AGI tool may improve quality of immunophenotyping in individual laboratories, since high percentages of checks in normal samples are an alert on the quality of the internal p

Published
2021

6. 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

7. An extensive quality control and quality assurance (QC/QA) program significantly improves inter-laboratory concordance rates of flow-cytometric minimal residual disease assessment in acute lymphoblastic leukemia: An I-BFM-FLOW-network report

Author

Maurer-Granofszky, M, Schumich, A, Buldini, B, Gaipa, G, Kappelmayer, J, Mejstrikova, E, Karawajew, L, Rossi, J, Suzan, A, Agriello, E, Anastasiou-Grenzelia, T, Barcala, V, Barna, G, Batinic, D, Bourquin, J, Bruggemann, M, Bukowska-Strakova, K, Burnusuzov, H, Carelli, D, Deniz, G, Dubravcic, K, Feuerstein, T, Gaillard, M, Galeano, A, Giordano, H, Gonzalez, A, Groeneveld-Krentz, S, Hevessy, Z, Hrusak, O, Iarossi, M, Jakso, P, Prevodnik, V, Kohlscheen, S, Kreminska, E, Maglia, O, Malusardi, C, Marinov, N, Martin, B, Moller, C, Nikulshin, S, Palazzi, J, Paterakis, G, Popov, A, Ratei, R, Rodriguez, C, Sajaroff, E, Sala, S, Samardzija, G, Sartor, M, Scarparo, P, Sedek, L, Slavkovic, B, Solari, L, Svec, P, Szczepanski, T, Taparkou, A, Torrebadell, M, Tzanoudaki, M, Varotto, E, Vernitsky, H, Attarbaschi, A, Schrappe, M, Conter, V, Biondi, A, Felice, M, Campbell, M, Kiss, C, Basso, G, Dworzak, M, Maurer-Granofszky M., Schumich A., Buldini B., Gaipa G., Kappelmayer J., Mejstrikova E., Karawajew L., Rossi J., Suzan A. C., Agriello E., Anastasiou-Grenzelia T., Barcala V., Barna G., Batinic D., Bourquin J. -P., Bruggemann M., Bukowska-Strakova K., Burnusuzov H., Carelli D., Deniz G., Dubravcic K., Feuerstein T., Gaillard M. I., Galeano A., Giordano H., Gonzalez A., Groeneveld-Krentz S., Hevessy Z., Hrusak O., Iarossi M. B., Jakso P., Prevodnik V. K., Kohlscheen S., Kreminska E., Maglia O., Malusardi C., Marinov N., Martin B. M., Moller C., Nikulshin S., Palazzi J., Paterakis G., Popov A., Ratei R., Rodriguez C., Sajaroff E. O., Sala S., Samardzija G., Sartor M., Scarparo P., Sedek L., Slavkovic B., Solari L., Svec P., Szczepanski T., Taparkou A., Torrebadell M., Tzanoudaki M., Varotto E., Vernitsky H., Attarbaschi A., Schrappe M., Conter V., Biondi A., Felice M., Campbell M., Kiss C., Basso G., Dworzak M. N., Maurer-Granofszky, M, Schumich, A, Buldini, B, Gaipa, G, Kappelmayer, J, Mejstrikova, E, Karawajew, L, Rossi, J, Suzan, A, Agriello, E, Anastasiou-Grenzelia, T, Barcala, V, Barna, G, Batinic, D, Bourquin, J, Bruggemann, M, Bukowska-Strakova, K, Burnusuzov, H, Carelli, D, Deniz, G, Dubravcic, K, Feuerstein, T, Gaillard, M, Galeano, A, Giordano, H, Gonzalez, A, Groeneveld-Krentz, S, Hevessy, Z, Hrusak, O, Iarossi, M, Jakso, P, Prevodnik, V, Kohlscheen, S, Kreminska, E, Maglia, O, Malusardi, C, Marinov, N, Martin, B, Moller, C, Nikulshin, S, Palazzi, J, Paterakis, G, Popov, A, Ratei, R, Rodriguez, C, Sajaroff, E, Sala, S, Samardzija, G, Sartor, M, Scarparo, P, Sedek, L, Slavkovic, B, Solari, L, Svec, P, Szczepanski, T, Taparkou, A, Torrebadell, M, Tzanoudaki, M, Varotto, E, Vernitsky, H, Attarbaschi, A, Schrappe, M, Conter, V, Biondi, A, Felice, M, Campbell, M, Kiss, C, Basso, G, Dworzak, M, Maurer-Granofszky M., Schumich A., Buldini B., Gaipa G., Kappelmayer J., Mejstrikova E., Karawajew L., Rossi J., Suzan A. C., Agriello E., Anastasiou-Grenzelia T., Barcala V., Barna G., Batinic D., Bourquin J. -P., Bruggemann M., Bukowska-Strakova K., Burnusuzov H., Carelli D., Deniz G., Dubravcic K., Feuerstein T., Gaillard M. I., Galeano A., Giordano H., Gonzalez A., Groeneveld-Krentz S., Hevessy Z., Hrusak O., Iarossi M. B., Jakso P., Prevodnik V. K., Kohlscheen S., Kreminska E., Maglia O., Malusardi C., Marinov N., Martin B. M., Moller C., Nikulshin S., Palazzi J., Paterakis G., Popov A., Ratei R., Rodriguez C., Sajaroff E. O., Sala S., Samardzija G., Sartor M., Scarparo P., Sedek L., Slavkovic B., Solari L., Svec P., Szczepanski T., Taparkou A., Torrebadell M., Tzanoudaki M., Varotto E., Vernitsky H., Attarbaschi A., Schrappe M., Conter V., Biondi A., Felice M., Campbell M., Kiss C., Basso G., and Dworzak M. N.

Abstract

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

Published
2021

8. P359: IMPROVED OVERALL SURVIVAL AND MRD CLEARANCE WITH BLINATUMOMAB VS CHEMOTHERAPY AS PRE-TRANSPLANT CONSOLIDATION IN PEDIATRIC HIGH-RISK FIRST-RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL)

Author

Locatelli, F., primary, Zugmaier, G., additional, Rizzari, C., additional, Morris, J., additional, Gruhn, B., additional, Klingebiel, T., additional, Parasole, R., additional, Linderkamp, C., additional, Flotho, C., additional, Petit, A., additional, Micalizzi, C., additional, Zeng, Y., additional, Desai, R., additional, Kormany, W., additional, Eckert, C., additional, Möricke, A., additional, Sartor, M., additional, Hrusak, O., additional, Peters, C., additional, Saha, V., additional, Vinti, L., additional, and von Stackelberg, A., additional

Published
2022
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11. RT-PCR-Based Detection of TEL/AML1 Fusion Transcript in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia — a Czech Childhood Leukemia Working Group Experience

Author

Childhood Leukemia Working Group, Trka, J., Zuna, J., Kalinova, M., Hrusak, O., Paukertova, R., Eckschlager, T., Stary, J., Hiddemann, W., editor, Büchner, T., editor, Wörmann, B., editor, Ritter, J., editor, Creutzig, U., editor, Keating, M., editor, and Plunkett, W., editor

Published
1998
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14. Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment

Author

Hrusak, O, Kalina, T, Wolf, J, Balduzzi, A, Provenzi, M, Rizzari, C, Rives, S, del Pozo Carlavilla, M, Alonso, M, Dominguez-Pinilla, N, Bourquin, J, Schmiegelow, K, Attarbaschi, A, Grillner, P, Mellgren, K, van der Werff ten Bosch, J, Pieters, R, Brozou, T, Borkhardt, A, Escherich, G, Lauten, M, Stanulla, M, Smith, O, Yeoh, A, Elitzur, S, Vora, A, Li, C, Ariffin, H, Kolenova, A, Dallapozza, L, Farah, R, Lazic, J, Manabe, A, Styczynski, J, Kovacs, G, Ottoffy, G, Felice, M, Buldini, B, Conter, V, Stary, J, Schrappe, M, Hrusak O., Kalina T., Wolf J., Balduzzi A., Provenzi M., Rizzari C., Rives S., del Pozo Carlavilla M., Alonso M. E. V., Dominguez-Pinilla N., Bourquin J. -P., Schmiegelow K., Attarbaschi A., Grillner P., Mellgren K., van der Werff ten Bosch J., Pieters R., Brozou T., Borkhardt A., Escherich G., Lauten M., Stanulla M., Smith O., Yeoh A. E. J., Elitzur S., Vora A., Li C. -K., Ariffin H., Kolenova A., Dallapozza L., Farah R., Lazic J., Manabe A., Styczynski J., Kovacs G., Ottoffy G., Felice M. S., Buldini B., Conter V., Stary J., Schrappe M., Hrusak, O, Kalina, T, Wolf, J, Balduzzi, A, Provenzi, M, Rizzari, C, Rives, S, del Pozo Carlavilla, M, Alonso, M, Dominguez-Pinilla, N, Bourquin, J, Schmiegelow, K, Attarbaschi, A, Grillner, P, Mellgren, K, van der Werff ten Bosch, J, Pieters, R, Brozou, T, Borkhardt, A, Escherich, G, Lauten, M, Stanulla, M, Smith, O, Yeoh, A, Elitzur, S, Vora, A, Li, C, Ariffin, H, Kolenova, A, Dallapozza, L, Farah, R, Lazic, J, Manabe, A, Styczynski, J, Kovacs, G, Ottoffy, G, Felice, M, Buldini, B, Conter, V, Stary, J, Schrappe, M, Hrusak O., Kalina T., Wolf J., Balduzzi A., Provenzi M., Rizzari C., Rives S., del Pozo Carlavilla M., Alonso M. E. V., Dominguez-Pinilla N., Bourquin J. -P., Schmiegelow K., Attarbaschi A., Grillner P., Mellgren K., van der Werff ten Bosch J., Pieters R., Brozou T., Borkhardt A., Escherich G., Lauten M., Stanulla M., Smith O., Yeoh A. E. J., Elitzur S., Vora A., Li C. -K., Ariffin H., Kolenova A., Dallapozza L., Farah R., Lazic J., Manabe A., Styczynski J., Kovacs G., Ottoffy G., Felice M. S., Buldini B., Conter V., Stary J., and Schrappe M.

Abstract

Introduction: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. Aim and methods: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. Results: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. Conclusion: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.

Published
2020

18. Childhood secondary ALL after ALL treatment

Author

Zuna, J, Cavé, H, Eckert, C, Szczepanski, T, Meyer, C, Mejstrikova, E, Fronkova, E, Muzikova, K, Clappier, E, Mendelova, D, Boutard, P, Schrauder, A, Sterba, J, Marschalek, R, van Dongen, J J M, Hrusak, O, Stary, J, and Trka, J

Published
2007
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20. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes

Author

van Dongen, J JM, Lhermitte, L, Böttcher, S, Almeida, J, van der Velden, V HJ, Flores-Montero, J, Rawstron, A, Asnafi, V, Lécrevisse, Q, Lucio, P, Mejstrikova, E, Szczepański, T, Kalina, T, de Tute, R, Brüggemann, M, Sedek, L, Cullen, M, Langerak, A W, Mendonça, A, Macintyre, E, Martin-Ayuso, M, Hrusak, O, Vidriales, M B, and Orfao, A

Published
2012
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24. Blood monitoring of circulating tumor plasma cells by next generation flow in multiple myeloma after therapy

Author

Sanoja-Flores, L., Flores-Montero, J., Puig, N., Contreras-Sanfeliciano, T., Pontes, R., Corral-Mateos, A., Garcia-Sanchez, O., Diez-Campelo, M., Magalhaes, R.J.P. de, Garcia-Martin, L., Alonso-Alonso, J.M., Garcia-Mateo, A., Aguilar-Franco, C., Labrador, J., Barez-Garcia, A., Maiolino, A., Paiva, B., San Miguel, J., Costa, E.S. da, Gonzalez, M., Mateos, M.V., Durie, B., Dongen, J.J.M. van, Orfao, A., Bitter, W.M., Lubbers, B.R., Meij, A.S.M. van der, Teodosio, C.I., Zlei, M., Sluijs-Gelling, A.J. van der, Burg, M. van der, Velden, V.H.J. van der, Langerak, A.W., Marvelde, J. te, Schilperoord-Vermeulen, J., Blijkerk, A., Heezen, K.C., Almeida, J., Vidriales, M.B., Perez-Andres, J.F.M.M., Matarraz, S., Blanco, E., Martin, L., Lecrevisse, Q., Perez-Moran, J.J., Almeida, A.M., Silva, M.G. da, Faria, T., Bruggemann, M., Ritgen, M., Szczepanowski, M., Kohlscheen, S., Steinert, A., Harbst, E., Finke, J., Asnafi, V., Lhermitte, L., Duroyon, E., Trka, J., Hrusak, O., Kalina, T., Mejstrikova, E., Novakova, M., Thurner, D., Kanderova, V., Szczepanski, T., Sedek, L., Bulsa, J., Slota, L., Kulis, J., Pedreira, C.E., Nierkens, S., Jong, A. de, Koning, A. de, Lima, M., Santos, A.H., Bottcher, S., Lange, S., Engelmann, R., Paape, D., Machka, C., Gaipa, G., Burracchi, C., Bugarin, C., Lopez-Granados, E., Molina, L.D., Vlkova, M., Nechvatalova, J., Roussel, M., Campos-Guyotat, L., Aanei, C., Burgos, L., Villamor-Casas, N., Magnano, L., Philippe, J., Bonroy, C., Denys, B., Willems, A., Breughe, P., Wolf, J. de, Sousa, A.E., Silva, S.L., Fernandez, P., Morf, D., EuroFlow Consortium, and Immunology

Subjects
Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Immunology, Plasma Cells, Cell Biology, Hematology, medicine.disease, Flow Cytometry, Neoplastic Cells, Circulating, Prognosis, Biochemistry, Flow cytometry, Immunophenotyping, Text mining, Flow (mathematics), medicine, Humans, business, Multiple Myeloma, Letter to Blood, Multiple myeloma
Published
2019

27. COVID-19 - Impact on Childhood Haematology Patients

Author

Wolfs, T, Attarbaschi, A, Balduzzi, A, Bernardo, M, Bomken, S, Borkhardt, A, Bourquin, J, Dufour, C, Gennery, A, Grainger, J, Hasle, H, Hrusak, O, Izraeli, S, Mechinaud, F, Trka, J, Vormoor, J, Wolfs, Tom F W, Attarbaschi, Andishe, Balduzzi, Adriana, Bernardo, Maria Ester, Bomken, Simon, Borkhardt, Arndt, Bourquin, Jean-Pierre, Dufour, Carlo, Gennery, Andrew, Grainger, John, Hasle, Henrik, Hrusak, Ondrej, Izraeli, Shai, Mechinaud, Francoise, Trka, Jan, Vormoor, Josef, Wolfs, T, Attarbaschi, A, Balduzzi, A, Bernardo, M, Bomken, S, Borkhardt, A, Bourquin, J, Dufour, C, Gennery, A, Grainger, J, Hasle, H, Hrusak, O, Izraeli, S, Mechinaud, F, Trka, J, Vormoor, J, Wolfs, Tom F W, Attarbaschi, Andishe, Balduzzi, Adriana, Bernardo, Maria Ester, Bomken, Simon, Borkhardt, Arndt, Bourquin, Jean-Pierre, Dufour, Carlo, Gennery, Andrew, Grainger, John, Hasle, Henrik, Hrusak, Ondrej, Izraeli, Shai, Mechinaud, Francoise, Trka, Jan, and Vormoor, Josef

Published
2020

31. Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia

Author

Lhermitte, L., Mejstrikova, E., Sluijs-Gelling, A.J. van der, Grigore, G.E., Sedek, L., Bras, A.E., Gaipa, G., Costa, E.S. da, Novakova, M., Sonneveld, E., Buracchi, C., Bacelar, T.D., Marvelde, J.G.T., Trinquand, A., Asnafi, V., Szczepanski, T., Matarraz, S., Lopez, A., Vidriales, B., Bulsa, J., Hrusak, O., Kalina, T., Lecrevisse, Q., Ayuso, M.M., Bruggemann, M., Verde, J., Fernandez, P., Burgos, L., Paiva, B., Pedreira, C.E., Dongen, J.J.M. van, Orfao, A., Velden, V.H.J. van der, EuroFlow Consortium, Instituto de Salud Carlos III, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Ministerio de Sanidad y Consumo (España), Polish Academy of Sciences, Fundações de Amparo à Pesquisa (Brasil), Ministerio de Economía y Competitividad (España), Immunology, Lhermitte, L, Mejstrikova, E, Van Der Sluijs-Gelling, A, Grigore, G, Sedek, L, Bras, A, Gaipa, G, Sobral Da Costa, E, Novakova, M, Sonneveld, E, Buracchi, C, De Sa Bacelar, T, Te Marvelde, J, Trinquand, A, Asnafi, V, Szczepanski, T, Matarraz, S, Lopez, A, Vidriales, B, Bulsa, J, Hrusak, O, Kalina, T, Lecrevisse, Q, Martin Ayuso, M, Bruggemann, M, Verde, J, Fernandez, P, Burgos, L, Paiva, B, Pedreira, C, Van Dongen, J, Orfao, A, and Van Der Velden, V

Subjects
Adult, Male, 0301 basic medicine, Cancer Research, Myeloid, Adolescent, T-cell acute lymphoblastic leukemia (T-ALL), Immunophenotyping, Young Adult, 03 medical and health sciences, Text mining, Acute leukemia (AL), EuroFlow, medicine, Humans, AL orientation tube (ALOT), Child, Aged, Aged, 80 and over, Acute leukemia, Leukemia, business.industry, Orientation (computer vision), Infant, Newborn, Infant, Myeloid leukemia, Pattern recognition, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Leukemia, Myeloid, Acute, Statistical classification, 030104 developmental biology, medicine.anatomical_structure, Oncology, Child, Preschool, Acute Disease, B-cell precursor (BCP), Female, Original Article, Artificial intelligence, business
Abstract

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications., The research was performed within the EuroFlow Consortium, which started with an EU-FP6 grant (LSHB-CT-2006-018708) and obtained sustainability by protecting and licensing intellectual property, thereby obtaining royalties, which are exclusively being used for supporting the EuroFlow research program (chairmen: JJMvD and AO). LS, JB and TS were supported by STRATEGMED3/304586/5/NCBR/2017 PersonALL grant of the Polish National Center for Research and Development. ESC acknowledges FAPERJ, Rio de Janeiro, Brazil (E26/110.105/2014; E26/102.191/2013) and Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPQ of Brazil (400194/2014-7). AO, SM and AL acknowledge the Instituto de Salud Carlos III (MINECO, Madrid, Spain) for the DTS15/00119, and CIBERONC-FEDER-CB16/12/00400 grants. EM, OH, TK and MN were supported by Ministry of Health grant number 15-28525A and NPU LO1604. The research for this manuscript was in part performed within the framework of the Erasmus Postgraduate School Molecular Medicine.

Published
2018

32. AIEOP-BFM consensus guidelines 2016 for flow cytometric immunophenotyping of Pediatric acute lymphoblastic leukemia

Author

Dworzak, M, Buldini, B, Gaipa, G, Ratei, R, Hrusak, O, Luria, D, Rosenthal, E, Bourquin, J, Sartor, M, Schumich, A, Karawajew, L, Mejstrikova, E, Maglia, O, Mann, G, Ludwig, W, Biondi, A, Schrappe, M, Basso, G, Dworzak, M, Buldini, B, Gaipa, G, Ratei, R, Hrusak, O, Luria, D, Rosenthal, E, Bourquin, J, Sartor, M, Schumich, A, Karawajew, L, Mejstrikova, E, Maglia, O, Mann, G, Ludwig, W, Biondi, A, Schrappe, M, and Basso, G

Subjects
standardization, flow cytometry, immunophenotyping, leukemia, pediatric, 2734, Histology, Cell Biology, Consensus, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Immunophenotyping, Phenotype, Acute Disease, Humans, Child
Abstract

Immunophenotyping by flow cytometry (FCM) is a worldwide mainstay in leukemia diagnostics. For concordant multicentric application, however, a gap exists between available classification systems, technologic standardization, and clinical needs. The AIEOP-BFM consortium induced an extensive standardization and validation effort between its nine national reference laboratories collaborating in immunophenotyping of pediatric acute lymphoblastic leukemia (ALL). We elaborated common guidelines which take advantage of the possibilities of multi-color FCM: marker panel requirements, immunological blast gating, in-sample controls, tri-partite antigen expression rating (negative vs. weak or strong positive) with capturing of blast cell heterogeneities and subclone formation, refined ALL subclassification, and a dominant lineage assignment algorithm able to distinguish “simple” from bilineal/“complex” mixed phenotype acute leukemia (MPAL) cases, which is essential for choice of treatment. These guidelines are a first step toward necessary inter-laboratory standardization of pediatric leukemia immunophenotyping for a concordant multicentric application. © 2017 International Clinical Cytometry Society.

Published
2018

33. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia

Author

Theunissen, P, Mejstrikova, E, Sedek, L, Van Der Sluijs-Gelling, A, Gaipa, G, Bartels, M, Sobral da Costa, E, Kotrova, M, Novakova, M, Sonneveld, E, Buracchi, C, Bonaccorso, P, Oliveira, E, Te Marvelde, J, Szczepanski, T, Lhermitte, L, Hrusak, O, Lecrevisse, Q, Grigore, G, Fronkova, E, Trka, J, Bruggemann, M, Orfao, A, Van Dongen, J, Van Der Velden, V, Theunissen P., Mejstrikova E., Sedek L., Van Der Sluijs-Gelling A. J., Gaipa G., Bartels M., Sobral da Costa E., Kotrova M., Novakova M., Sonneveld E., Buracchi C., Bonaccorso P., Oliveira E., Te Marvelde J. G., Szczepanski T., Lhermitte L., Hrusak O., Lecrevisse Q., Grigore G. E., Fronkova E., Trka J., Bruggemann M., Orfao A., Van Dongen J. J. M., Van Der Velden V. H. J., Theunissen, P, Mejstrikova, E, Sedek, L, Van Der Sluijs-Gelling, A, Gaipa, G, Bartels, M, Sobral da Costa, E, Kotrova, M, Novakova, M, Sonneveld, E, Buracchi, C, Bonaccorso, P, Oliveira, E, Te Marvelde, J, Szczepanski, T, Lhermitte, L, Hrusak, O, Lecrevisse, Q, Grigore, G, Fronkova, E, Trka, J, Bruggemann, M, Orfao, A, Van Dongen, J, Van Der Velden, V, Theunissen P., Mejstrikova E., Sedek L., Van Der Sluijs-Gelling A. J., Gaipa G., Bartels M., Sobral da Costa E., Kotrova M., Novakova M., Sonneveld E., Buracchi C., Bonaccorso P., Oliveira E., Te Marvelde J. G., Szczepanski T., Lhermitte L., Hrusak O., Lecrevisse Q., Grigore G. E., Fronkova E., Trka J., Bruggemann M., Orfao A., Van Dongen J. J. M., and Van Der Velden V. H. J.

Abstract

A fully-standardized EuroFlow 8–color antibody panel and laboratory procedure was stepwise designed to measure minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients with a sensitivity of £1025, comparable to real-time quantitative polymerase chain reaction (RQ-PCR)–based MRD detection via antigen-receptor rearrangements. Leukocyte markers and the corresponding antibodies and fluorochromes were selected based on their contribution in separating BCP-ALL cells from normal/regenerating BCP cells in multidimensional principal component analyses. After 5 multicenter design-test-evaluate-redesign phases with a total of 319 BCP-ALL patients at diagnosis, two 8-color antibody tubes were selected, which allowed separation between normal and malignant BCP cells in 99% of studied patients. These 2 tubes were tested with a new erythrocyte bulk-lysis protocol allowing acquisition of high cell numbers in 377 bone marrow follow-up samples of 178 BCP-ALL patients. Comparison with RQ-PCR–based MRD data showed a clear positive relation between the percentage concordant cases and the number of cells acquired. For those samples with >4 million cells acquired, concordant results were obtained in 93% of samples. Most discordances were clarified upon high-throughput sequencing of antigen-receptor rearrangements and blind multicenter reanalysis of flow cytometric data, resulting in an unprecedented concordance of 98% (97% for samples with MRD < 0.01%). In conclusion, the fully standardized EuroFlow BCP-ALL MRD strategy is applicable in >98% of patients with sensitivities at least similar to RQ-PCR (£1025), if sufficient cells (>4 3 106, preferably more) are evaluated.

Published
2017

35. PB1651 INFERIOR PROGNOSIS OF TLX3 GENE REARRANGEMENTS IN PEDIATRIC T-ALL

Author

Lizcova, L., primary, Prihodova, E., additional, Pavlistova, L., additional, Sladkova, L., additional, Svobodova, K., additional, Mejstrikova, E., additional, Hrusak, O., additional, Luknarova, P., additional, Janotova, I., additional, Sramkova, L., additional, Stary, J., additional, Michalova, K., additional, and Zemanova, Z., additional

Published
2019
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36. PF237 THE PROGNOSTIC IMPACT OF LYMPHOCYTE REPERTOIRE RECOVERY AFTER INDUCTION TREATMENT OF CHILDHOOD AML

Author

Svaton, M., primary, Novakova, M., additional, Reznickova, L., additional, Darzentas, N., additional, Stuchly, J., additional, Svenkrtova, A., additional, Zaliova, M., additional, Zuna, J., additional, Mejstrikova, E., additional, Kotrova, M., additional, Reigl, T., additional, Hrusak, O., additional, Stary, J., additional, Trka, J., additional, and Fronkova, E., additional

Published
2019
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37. PF176 MONOCYTIC SWITCH AND DISCREPANCY BETWEEN FLOW CYTOMETRIC AND MOLECULAR MINIMAL RESIDUAL DISEASE ARE FREQUENT IN DUX4 REARRANGED AND PAX5-P80R MUTATED B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA

Author

Novakova, M., primary, Vakrmanova, B., additional, Slamova, L., additional, Musilova, A., additional, Bruggemann, M., additional, Ritgen, M., additional, Kolenovska, A., additional, Svec, P., additional, Fronkova, E., additional, Kalina, T., additional, Trka, J., additional, Stary, J., additional, Vaskova, M., additional, Winkowska, L., additional, Zaliova, M., additional, Fiser, K., additional, Hrusak, O., additional, and Mejstrikova, E., additional

Published
2019
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38. CD19 and CD22-directed biespecific CAR for B-cell Acute Lymphoblastic Leukemia

Author

Zanetti, SR, additional, Velazco-Hernandez, T, additional, Gutierrez-Agüera, F, additional, Roca-Ho, H, additional, Sánchez-Martínez, D, additional, Petazzi, P, additional, Torres, R, additional, Molina, O, additional, Torrebadell-Burriel, M, additional, Vidriales-Vicente, MB, additional, Hrusak, O, additional, Fuster, JL, additional, Juan, M, additional, Bueno, C, additional, and Menéndez, P, additional

Published
2019
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39. International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

Author

Hrusak, O. De Haas, V. Stancikova, J. Vakrmanova, B. Janotova, I. Mejstrikova, E. Capek, V. Trka, J. Zaliova, M. Luks, A. Bleckmann, K. Möricke, A. Irving, J. Konatkowska, B. Alexander, T.B. Inaba, H. Schmiegelow, K. Stokley, S. Zemanova, Z. Moorman, A.V. Rossi, J.G. Felice, M.S. Dalla-Pozza, L. Morales, J. Dworzak, M. Buldini, B. Basso, G. Campbell, M. Cabrera, M.E. Marinov, N. Elitzur, S. Izraeli, S. Luria, D. Feuerstein, T. Kolenova, A. Svec, P. Kreminska, O. Rabin, K.R. Polychronopoulou, S. Da Costa, E. Marquart, H.V. Kattamis, A. Ratei, R. Reinhardt, D. Choi, J.K. Schrappe, M. Stary, J.

Subjects
hemic and lymphatic diseases
Abstract

Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Münster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80% 6 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% 6 7.2% and 50% 6 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD191 leukemia was 83% 6 5.3% on ALL-type primary treatment compared with 0% 6 0% and 28% 6 14% on AML-type and combined-type primary treatment, respectively. Superiority , of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization . and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD191 ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD192 and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ‡5% blasts after remission induction. The results provide a basis for a prospective trial. (Blood. 2018;132(3):264-276) © American Society of Hematology. All rights reserved.

Published
2018

40. Customized or randomized trials for relapsed refractory pediatric Burkitt lymphomas? A retrospective analysis of two clinical cases with comprehensive molecular profiling: Possible explanation for different treatment outcomes after similar targeted therapies

Author

Polaskova, K., primary, Martincekova, A., additional, Krenova, Z., additional, Valik, D., additional, Noskova, H., additional, Slaby, O., additional, Kanderova, V., additional, Hrusak, O., additional, Klement, G.L., additional, Neradil, J., additional, Veselska, R., additional, and Sterba, J., additional

Published
2018
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41. Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia

Author

Lhermitte, L, Mejstrikova, E, Van Der Sluijs-Gelling, A, Grigore, G, Sedek, L, Bras, A, Gaipa, G, Sobral Da Costa, E, Novakova, M, Sonneveld, E, Buracchi, C, De Sa Bacelar, T, Te Marvelde, J, Trinquand, A, Asnafi, V, Szczepanski, T, Matarraz, S, Lopez, A, Vidriales, B, Bulsa, J, Hrusak, O, Kalina, T, Lecrevisse, Q, Martin Ayuso, M, Bruggemann, M, Verde, J, Fernandez, P, Burgos, L, Paiva, B, Pedreira, C, Van Dongen, J, Orfao, A, Van Der Velden, V, Lhermitte, L, Mejstrikova, E, Van Der Sluijs-Gelling, A, Grigore, G, Sedek, L, Bras, A, Gaipa, G, Sobral Da Costa, E, Novakova, M, Sonneveld, E, Buracchi, C, De Sa Bacelar, T, Te Marvelde, J, Trinquand, A, Asnafi, V, Szczepanski, T, Matarraz, S, Lopez, A, Vidriales, B, Bulsa, J, Hrusak, O, Kalina, T, Lecrevisse, Q, Martin Ayuso, M, Bruggemann, M, Verde, J, Fernandez, P, Burgos, L, Paiva, B, Pedreira, C, Van Dongen, J, Orfao, A, and Van Der Velden, V

Abstract

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications.

Published
2018

42. The genetic basis and cell of origin of mixed phenotype acute leukaemia.

Author

Alexander, TB, Gu, Z, Iacobucci, I, Dickerson, K, Choi, JK, Xu, B, Payne-Turner, D, Yoshihara, H, Loh, ML, Horan, J, Buldini, B, Basso, G, Elitzur, S, de Haas, V, Zwaan, CM, Yeoh, A, Reinhardt, D, Tomizawa, D, Kiyokawa, N, Lammens, T, De Moerloose, B, Catchpoole, D, Hori, H, Moorman, A, Moore, AS, Hrusak, O, Meshinchi, S, Orgel, E, Devidas, M, Borowitz, M, Wood, B, Heerema, NA, Carrol, A, Yang, Y-L, Smith, MA, Davidsen, TM, Hermida, LC, Gesuwan, P, Marra, MA, Ma, Y, Mungall, AJ, Moore, RA, Jones, SJM, Valentine, M, Janke, LJ, Rubnitz, JE, Pui, C-H, Ding, L, Liu, Y, Zhang, J, Nichols, KE, Downing, JR, Cao, X, Shi, L, Pounds, S, Newman, S, Pei, D, Guidry Auvil, JM, Gerhard, DS, Hunger, SP, Inaba, H, Mullighan, CG, Alexander, TB, Gu, Z, Iacobucci, I, Dickerson, K, Choi, JK, Xu, B, Payne-Turner, D, Yoshihara, H, Loh, ML, Horan, J, Buldini, B, Basso, G, Elitzur, S, de Haas, V, Zwaan, CM, Yeoh, A, Reinhardt, D, Tomizawa, D, Kiyokawa, N, Lammens, T, De Moerloose, B, Catchpoole, D, Hori, H, Moorman, A, Moore, AS, Hrusak, O, Meshinchi, S, Orgel, E, Devidas, M, Borowitz, M, Wood, B, Heerema, NA, Carrol, A, Yang, Y-L, Smith, MA, Davidsen, TM, Hermida, LC, Gesuwan, P, Marra, MA, Ma, Y, Mungall, AJ, Moore, RA, Jones, SJM, Valentine, M, Janke, LJ, Rubnitz, JE, Pui, C-H, Ding, L, Liu, Y, Zhang, J, Nichols, KE, Downing, JR, Cao, X, Shi, L, Pounds, S, Newman, S, Pei, D, Guidry Auvil, JM, Gerhard, DS, Hunger, SP, Inaba, H, and Mullighan, CG

Abstract

Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with myeloid and lymphoid features, limited genetic characterization, and a lack of consensus regarding appropriate therapy. Here we show that the two principal subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct. Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are common in T/M MPAL, which shares genomic features with early T-cell precursor acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic heterogeneity characteristic of MPAL is independent of somatic genetic variation, that founding lesions arise in primitive haematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. These findings indicate that the cell of origin and founding lesions, rather than an accumulation of distinct genomic alterations, prime tumour cells for lineage promiscuity. Moreover, these findings position MPAL in the spectrum of immature leukaemias and provide a genetically informed framework for future clinical trials of potential treatments for MPAL.

Published
2018

43. Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome

Author

Novakova, M, Zaliova, M, Sukova, M, Wlodarski, M, Janda, A, Fronkova, E, Campr, V, Lejhancova, K, Zapletal, O, Pospisilova, D, Cerna, Z, Kuhn, T, Svec, P, Pelkova, V, Zemanova, Z, Kerndrup, G, Van den Heuvel - Eibrink, Marry, van der Velden, Vincent, Niemeyer, C, Kalina, T, Trka, J, Stary, J, Hrusak, O, Mejstrikova, E, and Immunology

Subjects
B-Lymphocytes, Adolescent, Precursor Cells, B-Lymphoid, Anemia, Aplastic, Infant, Bone Marrow Cells, Article, Immunophenotyping, Diagnosis, Differential, GATA2 Transcription Factor, Young Adult, Phenotype, ROC Curve, Bone Marrow, T-Lymphocyte Subsets, hemic and lymphatic diseases, Child, Preschool, Lymphopenia, Myelodysplastic Syndromes, Mutation, Humans, Myeloid Cells, Lymphocyte Count, Child, Biomarkers
Abstract

GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).

Published
2016

45. Standardized Next-Generation Flow Cytometry for Highly Sensitive Mrd Measurements in B-Cell Acute Lymphoblastic Leukemia

Author

Theunissen, Prisca, Mejstrikova, E, Sedek, L, van der Sluijs, A, Gaipa, G, Bartels, M, Sobral de Costa, E, Kotrova, M, Novakova, M, Sonneveld, E, Baracchi, C, Bonaccorso, P, Oliviera, E, te Marvelde, Jeroen, Szczepanski, Tomek, Lhermitte, L, Hrusak, O, Lecrevisse, Q, Grigore, GE, Fronkova, E, Trka, J, Bruggemann, M, Orfao, A, Dongen, Jacques, van der Velden, Vincent, van Dongen, JJM, Immunology, and Plastic and Reconstructive Surgery and Hand Surgery

Published
2016

46. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia

Author

Theunissen, Prisca, Mejstrikova, E, Sedek, L, van der Sluijs-Gelling, AJ, Gaipa, G, Bartels, M, Costa, ES, Kotrova, M, Novakova, M, Sonneveld, E, Buracchi, C, Bonaccorso, P, Oliveira, E, te Marvelde, Jeroen, Szczepanski, T, Lhermitte, L, Hrusak, O, Lecrevisse, Q, Grigore, GE, Fronkova, E, Trka, J, Bruggemann, M, Orfao, A, Dongen, Jacques, van der Velden, Vincent, Theunissen, Prisca, Mejstrikova, E, Sedek, L, van der Sluijs-Gelling, AJ, Gaipa, G, Bartels, M, Costa, ES, Kotrova, M, Novakova, M, Sonneveld, E, Buracchi, C, Bonaccorso, P, Oliveira, E, te Marvelde, Jeroen, Szczepanski, T, Lhermitte, L, Hrusak, O, Lecrevisse, Q, Grigore, GE, Fronkova, E, Trka, J, Bruggemann, M, Orfao, A, Dongen, Jacques, and van der Velden, Vincent

Published
2017

48. Quality assessment program for EuroFlow protocols: summary results of four-year (2010-2013) quality assurance rounds

Author

Kalina, T, Flores-Montero, J, Lecrevisse, Q, Pedreira, CE, van der Velden, Vincent, Novakova, M, Mejstrikova, E, Hrusak, O, Bottcher, S, Karsch, D, Sedek, L, Trinquand, A, Boeckx, N, Caetano, J, Asnafi, V, Lucio, P, Lima, M, Santos, AH, Bonaccorso, P, van der Sluijs-Gelling, AJ, Langerak, Ton, Martin-Ayuso, M, Szczepanski, T, Dongen, Jacques, Orfao, A, and Immunology

Subjects
Europe, Quality Control, Leukemia, Lymphoma, Reference Values, Reference Standards, Flow Cytometry, Healthy Volunteers, Lymphocyte Subsets, Immunophenotyping
Abstract

Flow cytometric immunophenotyping has become essential for accurate diagnosis, classification, and disease monitoring in hemato-oncology. The EuroFlow Consortium has established a fully standardized "all-in-one" pipeline consisting of standardized instrument settings, reagent panels, and sample preparation protocols and software for data analysis and disease classification. For its reproducible implementation, parallel development of a quality assurance (QA) program was required. Here, we report on the results of four consecutive annual rounds of the novel external QA EuroFlow program. The novel QA scheme aimed at monitoring the whole flow cytometric analysis process (cytometer setting, sample preparation, acquisition and analysis) by reading the median fluorescence intensities (MedFI) of defined lymphocytes' subsets. Each QA participant applied the predefined reagents' panel on blood cells of local healthy donors. A uniform gating strategy was applied to define lymphocyte subsets and to read MedFI values per marker. The MedFI values were compared with reference data and deviations from reference values were quantified using performance score metrics. In four annual QA rounds, we analyzed 123 blood samples from local healthy donors on 14 different instruments in 11 laboratories from nine European countries. The immunophenotype of defined cellular subsets appeared sufficiently standardized to permit unified (software) data analysis. The coefficient of variation of MedFI for 7 of 11 markers performed repeatedly below 30%, average MedFI in each QA round ranged from 86 to 125% from overall median. Calculation of performance scores was instrumental to pinpoint standardization failures and their causes. Overall, the new EuroFlow QA system for the first time allowed to quantify the technical variation that is introduced in the measurement of fluorescence intensities in a multicentric setting over an extended period of time. EuroFlow QA is a proficiency test specific for laboratories that use standardized EuroFlow protocols. It may be used to complement, but not replace, established proficiency tests. © 2014 International Society for Advancement of Cytometry.

Published
2014

50. Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction

Author

Luk, CW, Lee, V, Leung, Y, Ng, MHL, Mejstrikova, E, Hrusak, O, Ling, SC, Li, CH, Lee, ACW, Cheuk, KLD, Ha, SY, Leung, AWK, Shing, MMK, Cheng, CK, Ip, RKL, Chan, NPH, Li, CK, Lau, KM, and Cheng, SH

Subjects
Oncology, Male, Pathology, Multivariate analysis, Neoplasm, Residual, Oncogene Proteins, Fusion, lcsh:Medicine, Pediatrics, Polymerase Chain Reaction, Hematologic Cancers and Related Disorders, Molecular cell biology, DNA amplification, Recurrence, hemic and lymphatic diseases, Blood plasma, Antineoplastic Combined Chemotherapy Protocols, Longitudinal Studies, Child, lcsh:Science, Multidisciplinary, medicine.diagnostic_test, Hematology, DNA, Neoplasm, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Flow Cytometry, Acute Lymphoblastic Leukemia, Prognosis, Nucleic acids, medicine.anatomical_structure, Real-time polymerase chain reaction, Child, Preschool, Cohort, Medicine, Female, Research Article, Risk, medicine.medical_specialty, Adolescent, Clinical Research Design, Antineoplastic Agents, Disease-Free Survival, Flow cytometry, Internal medicine, Leukemias, medicine, Humans, Pediatric Hematology, Statistical Methods, Immunoassays, Childhood Acute Lymphoblastic Leukemia, Biology, business.industry, lcsh:R, Infant, DNA, Minimal residual disease, body regions, Pediatric Oncology, Immunologic Techniques, Clinical Immunology, lcsh:Q, Bone marrow, business, Cytometry
Abstract

Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: 10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15

Published
2013

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