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291 results on '"Szczepanski T."'

1. Topological insulator and quantum memory

Author

Kulig, M., Kurashvili, P., Jasiukiewicz, C., Inglot, M., Wolski, S., Stagraczyński, S., Masłowski, T., Szczepański, T., Stagraczyński, R., Dugaev, V. K., and Chotorlishvili, L.

Subjects
Quantum Physics
Abstract

Measurements done on the quantum systems are too specific. Contrary to their classical counterparts, quantum measurements can be invasive and destroy the state of interest. Besides, quantumness limits the accuracy of measurements done on quantum systems. Uncertainty relations define the universal accuracy limit of the quantum measurements. Relatively recently, it was discovered that quantum correlations and quantum memory might reduce the uncertainty of quantum measurements. In the present work, we study two different types of measurements done on the topological system. Namely, we discuss measurements done on the spin operators and the canonical pair of operators: momentum and coordinate. We quantify the spin operator's measurements through the entropic measures of uncertainty and exploit the concept of quantum memory. While for the momentum and coordinate operators, we exploit the improved uncertainty relations. We discovered that quantum memory reduces the uncertainties of spin measurements. On the hand, we proved that the uncertainties in the measurements of the coordinate and momentum operators depend on the value of the momentum and are substantially enhanced at small distances between itinerant and localized electrons (the large momentum limit). We note that the topological nature of the system leads to the spin-momentum locking. The momentum of the electron depends on the spin and vice versa. Therefore, we suggest the indirect measurement scheme for the momentum and coordinate operators through the spin operator. Due to the factor of quantum memory, such indirect measurements in topological insulators have smaller uncertainties rather than direct measurements.

Published
2023

2. Random spin-orbit gates in the system of a Topological insulator and a Quantum dot

Author

Wolski, S., Inglot, M., Jasiukiewicz, C., Kouzakov, K. A., Masłowski, T., Szczepański, T., Stagraczyński, S., Stagraczyński, R., Dugaev, V. K., and Chotorlishvili, L.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Quantum Physics
Abstract

The spin-dependent scattering process in a system of topological insulator and quantum dot is studied. The unitary scattering process is viewed as a gate transformation applied to an initial state of two electrons. Due to the randomness imposed through the impurities and alloying-induced effects of band parameters, the formalism of the random unitary gates is implemented. For quantifying entanglement in the system, we explored concurrence and ensemble-averaged R\'enyi entropy. We found that applied external magnetic field leads to long-range entanglement on the distances much larger than the confinement length. We showed that topological features of itinerant electrons sustain the formation of robust long-distance entanglement, which survives even in the presence of a strong disorder., Comment: 12 pages, 8 figures

Published
2022
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3. Shot noise in magnetic tunneling structures with two-level quantum dots

Author

Szczepanski, T., Dugaev, V. K., Barnas, J., Martinez, I., Cascales, J. P., Hong, J. -Y., Lin, M. -T., and Aliev, F. G.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

We analyze shot noise in a magnetic tunnel junction with a two-level quantum dot attached to the magnetic electrodes. The considerations are limited to the case when some transport channels are suppressed at low temperatures. Coupling of the two dot's levels to the electrodes are assumed to be generally different and also spin-dependent. To calculate the shot noise we apply the approach based on the full counting statistics. The approach is used to account for experimental data obtained in magnetic tunnel junctions with organic barriers. The experimentally observed Fano factors correspond to the super-Poissonian statistics, and also depend on relative orientation of the electrodes' magnetic moments. We have also calculated the corresponding spin shot noise, which is associated with fluctuations of spin current.

Published
2017
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5. 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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6. Minimal residual disease assessment in B-cell precursor acute lymphoblastic leukemia by semi-automated identification of normal hematopoietic cells: A EuroFlow study

Author

Verbeek, M, Rodríguez, B, Sedek, L, Laqua, A, Buracchi, C, Buysse, M, Reiterová, M, Oliveira, E, Morf, D, Oude Alink, S, Barrena, S, Kohlscheen, S, Nierkens, S, Hofmans, M, Fernandez, P, de Costa, E, Mejstrikova, E, Szczepanski, T, Slota, L, Brüggemann, M, Gaipa, G, Grigore, G, van Dongen, J, Orfao, A, van der Velden, V, Verbeek M. W. C., Rodríguez B. S., Sedek L., Laqua A., Buracchi C., Buysse M., Reiterová M., Oliveira E., Morf D., Oude Alink S. R., Barrena S., Kohlscheen S., Nierkens S., Hofmans M., Fernandez P., de Costa E. S., Mejstrikova E., Szczepanski T., Slota L., Brüggemann M., Gaipa G., Grigore G., van Dongen J. J. M., Orfao A., van der Velden V. H. J., Verbeek, M, Rodríguez, B, Sedek, L, Laqua, A, Buracchi, C, Buysse, M, Reiterová, M, Oliveira, E, Morf, D, Oude Alink, S, Barrena, S, Kohlscheen, S, Nierkens, S, Hofmans, M, Fernandez, P, de Costa, E, Mejstrikova, E, Szczepanski, T, Slota, L, Brüggemann, M, Gaipa, G, Grigore, G, van Dongen, J, Orfao, A, van der Velden, V, Verbeek M. W. C., Rodríguez B. S., Sedek L., Laqua A., Buracchi C., Buysse M., Reiterová M., Oliveira E., Morf D., Oude Alink S. R., Barrena S., Kohlscheen S., Nierkens S., Hofmans M., Fernandez P., de Costa E. S., Mejstrikova E., Szczepanski T., Slota L., Brüggemann M., Gaipa G., Grigore G., van Dongen J. J. M., Orfao A., and van der Velden V. H. J.

Abstract

Presence of minimal residual disease (MRD), detected by flow cytometry, is an important prognostic biomarker in the management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, data-analysis remains mainly expert-dependent. In this study, we designed and validated an Automated Gating & Identification (AGI) tool for MRD analysis in BCP-ALL patients using the two tubes of the EuroFlow 8-color MRD panel. The accuracy, repeatability, and reproducibility of the AGI tool was validated in a multicenter study using bone marrow follow-up samples from 174 BCP-ALL patients, stained with the EuroFlow BCP-ALL MRD panel. In these patients, MRD was assessed both by manual analysis and by AGI tool supported analysis. Comparison of MRD levels obtained between both approaches showed a concordance rate of 83%, with comparable concordances between MRD tubes (tube 1, 2 or both), treatment received (chemotherapy versus targeted therapy) and flow cytometers (FACSCanto versus FACSLyric). After review of discordant cases by additional experts, the concordance increased to 97%. Furthermore, the AGI tool showed excellent intra-expert concordance (100%) and good inter-expert concordance (90%). In addition to MRD levels, also percentages of normal cell populations showed excellent concordance between manual and AGI tool analysis. We conclude that the AGI tool may facilitate MRD analysis using the EuroFlow BCP-ALL MRD protocol and will contribute to a more standardized and objective MRD assessment. However, appropriate training is required for the correct analysis of MRD data.

Published
2023

7. Controlling shot noise in double-barrier magnetic tunnel junctions

Author

Cascales, J. P., Herranz, D., Aliev, F. G., Szczepanski, T., Dugaev, V. K., Barnas, J., Duluard, A., Hehn, M., and Tiusan, C.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Materials Science
Abstract

We demonstrate that shot noise in Fe/MgO/Fe/MgO/Fe double-barrier magnetic tunnel junctions is determined by the relative magnetic configuration of the junction and also by the asymmetry of the barriers. The proposed theoretical model, based on sequential tunneling through the system and including spin relaxation, successfully accounts for the experimental observations for bias voltages below 0.5V, where the influence of quantum well states is negligible. A weak enhancement of conductance and shot noise, observed at some voltages (especially above 0.5V), indicates the formation of quantum well states in the middle magnetic layer. The observed results open up new perspectives for a reliable magnetic control of the most fundamental noise in spintronic structures., Comment: 8 pages, 4 figures

Published
2012
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8. A Case of Acute Myeloid Leukemia with Novel Translocation t(6;11)(p22.2;q23) and Concurrent Insertion ins(11;9)(q23;p21.3p21.3)

Author

Malinowska, I., Sikorska-Fic, B., Romiszewska, M., Stefaniak, A., Pastwińska, A., Górska, E., Popko, K., Meyer, C., Marschalek, R., Szczepański, T., COHEN, IRUN R., Series editor, LAJTHA, ABEL, Series editor, LAMBRIS, JOHN D., Series editor, PAOLETTI, RODOLFO, Series editor, Rezaei, Nima, Series editor, and Pokorski, Mieczyslaw, editor

Published
2017
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10. Global effort to evacuate Ukrainian children with cancer and blood disorders who have been affected by war

Author

Agulnik, A, Kizyma, R, Salek, M, Wlodarski, M, Pogorelyy, M, Oszer, A, Yakimkova, T, Nogovitsyna, Y, Dutkiewicz, M, Dalle, J, Dirksen, U, Eggert, A, Fernandez-Teijeiro, A, Greiner, J, Kraal, K, Mueller, A, Sramkova, L, Zecca, M, Wise, P, Mlynarski, W, Avula, M, Adyrov, M, Berlanga, P, Blackwood, C, Bouffet, E, Czauderna, P, de Koning, L, dos Reis Farinha, N, Foster, W, Graetz, D, Gupta, S, Holter, W, Hough, R, Kliuchkivska, K, Kolenova, A, Kolodrubiec, J, Moreira, D, Mukkada, S, Mykychak, I, Raciborska, A, Salman, Z, Sopilnyak, A, Tyupa, S, Vinitsky, A, Wobst, N, Miller, B, Rasul, S, Rodriguez-Galindo, C, Alanbousi, I, Alexander, S, Apel, A, Bal, W, Balwierz, W, Basset-Salom, L, Bastardo Blanco, D, Bauer, K, Bayazitov, I, Bhakta, N, Bien, E, Bieniek, K, Blair, S, Bodak, K, Bordeianu, I, Braganca, J, Bucurenci, M, Budny, E, Budzyn, A, Bumgardner, C, Burditt, R, Burnside Clapp, V, Bykov, V, Canete, A, Carnelli, M, Cela, E, Cepowska, Z, Chaber, R, Cherner-Drieux, A, Chubata, M, Clough, H, Czernicka - Siwecka, J, Czyzewski, K, Dashchakovska, O, Dembowska-Baginska, B, Derwich, K, Dommett, R, Dorosh, O, Drabko, K, Dragomir, M, Dworzak, M, Dyma, S, Earl, J, English, M, Evseev, D, Farren, B, Fedyk, N, Ferneza, S, Fox Irwin, L, Galazkowski, R, Ganieva, G, Garanzha, V, Gelman, M, Godzinski, J, Goeres, A, Golban, R, Griksaitis, M, Hampel, M, Hastings, S, Heenen, D, Hill, M, Holiuk, I, Hutnik, L, Irga-Jaworska, N, Istomin, O, Janczar, S, Kacharian, A, Kalwak, K, Karolczyk, G, Karpenko, N, Katsubo, H, Kaznowska, B, Kentsis, A, Ketteler, P, Kienesberger, A, Kiselev, R, Kizyma, Z, Klymniuk, H, Kostiuk, Y, Kowalik, T, Kozlova, O, Kozubenko, V, Kramar, T, Krawczuk-Rybak, M, Kulemzina, I, Kurkowska, P, Kuzyk, A, Ladenstein, R, Laguna, P, Lassaletta, A, Lehmberg, K, Leontieva, O, Liashenko, S, Loizou, L, Lucchetta, S, Lupo, M, Lysytsia, L, Lysytsia, O, Machnik, K, Mainland, J, Matczak, K, Matysiak, M, Mayeur, P, Minervina, A, Mishkova, V, Mizia-Malarz, A, Morales La Madrid, A, Moreno, L, Moskvin, V, Muszynska-Roslan, K, Nelson, A, Ociepa, T, Oltolini, S, Onipko, N, Pappas, A, Patel, A, Patrahau, A, Pauley, J, Pavlenko, Y, Pavlovych, A, Peregud-Pogorzelski, J, Perek-Polnik, M, Perez, V, Perez-Martinez, A, Pikman, Y, Pitozzi, G, Portugal, R, Posternak, V, Prete, A, Pritchard-Jones, K, Radaelli, A, Reeves, T, Reinhardt, D, Reshetnyak, A, Rider, A, Rizzari, C, Rizzi, D, Rodriguez Hermosillo, K, Ronenko, O, Rostowska, A, Rudko, L, Sakaan, F, Sakhar, N, Savva, N, Scaccaglia, D, Schaeffer, E, Schneider, C, Scobie, N, Semeniuk, O, Shevchyk, R, Shuler, A, Shvets, S, Skoczen, S, Smeal, W, Sokolowski, I, Sonkin, A, Stepanjuk, A, Spota, A, Sterba, J, Styczynski, J, Svintsova, O, Synyuta, A, Szczepanski, T, Szczucinski, P, Szmyd, B, Tasso Cereceda, M, Teliuk, A, Tomanek, I, Topping, P, Torrent, M, Trelinska, J, Troyanovska, O, Trubnikova, E, Tsurkan, L, Tsymbalyuk-Voloshyn, I, Urasinski, T, Urbanek-Dadela, A, Vasilieva, N, Vasilyeva, A, Verdu-Amoros, J, Vilcu-Bajurean, N, Vinitsky, L, Volpe, G, Vorobel, O, Wachowiak, J, Wasiak, M, Wiedower, L, Wuenschel, L, Wysocki, M, Yurieva, M, Zagurska, A, Zakharenko, S, Zakharenko, A, Zapotochna, K, Zawitkowska, J, Agulnik A., Kizyma R., Salek M., Wlodarski M. W., Pogorelyy M., Oszer A., Yakimkova T., Nogovitsyna Y., Dutkiewicz M., Dalle J. -H., Dirksen U., Eggert A., Fernandez-Teijeiro A., Greiner J., Kraal K., Mueller A., Sramkova L., Zecca M., Wise P. H., Mlynarski W., Avula M., Adyrov M. V., Berlanga P., Blackwood C. A., Bouffet E., Czauderna P. S., de Koning L. A., dos Reis Farinha N. J., Foster W. B., Graetz D. E., Gupta S., Holter W., Hough R. E., Kliuchkivska K., Kolenova A., Kolodrubiec J., Moreira D. C., Mukkada S. T., Mykychak I., Raciborska A., Salman Z. S., Sopilnyak A., Tyupa S., Vinitsky A., Wobst N. M., Miller B. A., Rasul S. S., Rodriguez-Galindo C., Alanbousi I., Alexander S. W., Apel A., Bal W. A., Balwierz W. A., Basset-Salom L., Bastardo Blanco D., Bauer K. J., Bayazitov I. T., Bhakta N. H., Bien E. I., Bieniek K. A., Blair S. J., Bodak K. I., Bordeianu I. M., Braganca J. M., Bucurenci M. S., Budny E. B., Budzyn A., Bumgardner C. C., Burditt R. N., Burnside Clapp V. G., Bykov V., Canete A., Carnelli M., Cela E., Cepowska Z. P., Chaber R., Cherner-Drieux A., Chubata M., Clough H. M., Czernicka - Siwecka J., Czyzewski K., Dashchakovska O., Dembowska-Baginska B. M., Derwich K., Dommett R., Dorosh O., Drabko K. A., Dragomir M. D., Dworzak M., Dyma S., Earl J. D., English M. W., Evseev D. A., Farren B. S., Fedyk N., Ferneza S., Fox Irwin L. E., Galazkowski R. M., Ganieva G., Garanzha V., Gelman M. S., Godzinski J. K., Goeres A. F., Golban R., Griksaitis M. J., Hampel M. A., Hastings S. G., Heenen D. L., Hill M. C., Holiuk I., Hutnik L. M., Irga-Jaworska N., Istomin O., Janczar S. L., Kacharian A., Kalwak K., Karolczyk G. M., Karpenko N. M., Katsubo H., Kaznowska B. J., Kentsis A., Ketteler P., Kienesberger A., Kiselev R., Kizyma Z., Klymniuk H., Kostiuk Y., Kowalik T., Kozlova O., Kozubenko V., Kramar T., Krawczuk-Rybak M., Kulemzina I., Kurkowska P., Kuzyk A. S., Ladenstein R. L., Laguna P. J., Lassaletta A., Lehmberg K., Leontieva O., Liashenko S., Loizou L. G., Lucchetta S. A., Lupo M. W., Lysytsia L., Lysytsia O., Machnik K. A., Mainland J. A., Matczak K. E., Matysiak M. J., Mayeur P., Minervina A. A., Mishkova V., Mizia-Malarz A. J., Morales La Madrid A., Moreno L., Moskvin V. P., Muszynska-Roslan K. M., Nelson A. J., Ociepa T., Oltolini S., Onipko N., Pappas A., Patel A. B., Patrahau A., Pauley J. L., Pavlenko Y., Pavlovych A., Peregud-Pogorzelski J., Perek-Polnik M., Perez V., Perez-Martinez A., Pikman Y., Pitozzi G., Portugal R. G., Posternak V. V., Prete A., Pritchard-Jones K., Radaelli A., Reeves T., Reinhardt D., Reshetnyak A. V., Rider A. J., Rizzari C., Rizzi D., Rodriguez Hermosillo K. G., Ronenko O., Rostowska A. O., Rudko L., Sakaan F. M., Sakhar N., Savva N. N., Scaccaglia D., Schaeffer E. H., Schneider C. U., Scobie N., Semeniuk O., Shevchyk R., Shuler A. I., Shvets S., Skoczen S. P., Smeal W. J., Sokolowski I., Sonkin A. A., Stepanjuk A. I., Spota A., Sterba J., Styczynski J., Svintsova O., Synyuta A. V., Szczepanski T., Szczucinski P. K., Szmyd B. M., Tasso Cereceda M., Teliuk A., Tomanek I., Topping P., Torrent M., Trelinska J., Troyanovska O., Trubnikova E., Tsurkan L. G., Tsymbalyuk-Voloshyn I., Urasinski T. F., Urbanek-Dadela A., Vasilieva N., Vasilyeva A., Verdu-Amoros J., Vilcu-Bajurean N., Vinitsky L., Volpe G., Vorobel O., Wachowiak J. T., Wasiak M. S., Wiedower L. A., Wuenschel L. I., Wysocki M. S., Yurieva M., Zagurska A., Zakharenko S. S., Zakharenko A. V., Zapotochna K., Zawitkowska J. E., Agulnik, A, Kizyma, R, Salek, M, Wlodarski, M, Pogorelyy, M, Oszer, A, Yakimkova, T, Nogovitsyna, Y, Dutkiewicz, M, Dalle, J, Dirksen, U, Eggert, A, Fernandez-Teijeiro, A, Greiner, J, Kraal, K, Mueller, A, Sramkova, L, Zecca, M, Wise, P, Mlynarski, W, Avula, M, Adyrov, M, Berlanga, P, Blackwood, C, Bouffet, E, Czauderna, P, de Koning, L, dos Reis Farinha, N, Foster, W, Graetz, D, Gupta, S, Holter, W, Hough, R, Kliuchkivska, K, Kolenova, A, Kolodrubiec, J, Moreira, D, Mukkada, S, Mykychak, I, Raciborska, A, Salman, Z, Sopilnyak, A, Tyupa, S, Vinitsky, A, Wobst, N, Miller, B, Rasul, S, Rodriguez-Galindo, C, Alanbousi, I, Alexander, S, Apel, A, Bal, W, Balwierz, W, Basset-Salom, L, Bastardo Blanco, D, Bauer, K, Bayazitov, I, Bhakta, N, Bien, E, Bieniek, K, Blair, S, Bodak, K, Bordeianu, I, Braganca, J, Bucurenci, M, Budny, E, Budzyn, A, Bumgardner, C, Burditt, R, Burnside Clapp, V, Bykov, V, Canete, A, Carnelli, M, Cela, E, Cepowska, Z, Chaber, R, Cherner-Drieux, A, Chubata, M, Clough, H, Czernicka - Siwecka, J, Czyzewski, K, Dashchakovska, O, Dembowska-Baginska, B, Derwich, K, Dommett, R, Dorosh, O, Drabko, K, Dragomir, M, Dworzak, M, Dyma, S, Earl, J, English, M, Evseev, D, Farren, B, Fedyk, N, Ferneza, S, Fox Irwin, L, Galazkowski, R, Ganieva, G, Garanzha, V, Gelman, M, Godzinski, J, Goeres, A, Golban, R, Griksaitis, M, Hampel, M, Hastings, S, Heenen, D, Hill, M, Holiuk, I, Hutnik, L, Irga-Jaworska, N, Istomin, O, Janczar, S, Kacharian, A, Kalwak, K, Karolczyk, G, Karpenko, N, Katsubo, H, Kaznowska, B, Kentsis, A, Ketteler, P, Kienesberger, A, Kiselev, R, Kizyma, Z, Klymniuk, H, Kostiuk, Y, Kowalik, T, Kozlova, O, Kozubenko, V, Kramar, T, Krawczuk-Rybak, M, Kulemzina, I, Kurkowska, P, Kuzyk, A, Ladenstein, R, Laguna, P, Lassaletta, A, Lehmberg, K, Leontieva, O, Liashenko, S, Loizou, L, Lucchetta, S, Lupo, M, Lysytsia, L, Lysytsia, O, Machnik, K, Mainland, J, Matczak, K, Matysiak, M, Mayeur, P, Minervina, A, Mishkova, V, Mizia-Malarz, A, Morales La Madrid, A, Moreno, L, Moskvin, V, Muszynska-Roslan, K, Nelson, A, Ociepa, T, Oltolini, S, Onipko, N, Pappas, A, Patel, A, Patrahau, A, Pauley, J, Pavlenko, Y, Pavlovych, A, Peregud-Pogorzelski, J, Perek-Polnik, M, Perez, V, Perez-Martinez, A, Pikman, Y, Pitozzi, G, Portugal, R, Posternak, V, Prete, A, Pritchard-Jones, K, Radaelli, A, Reeves, T, Reinhardt, D, Reshetnyak, A, Rider, A, Rizzari, C, Rizzi, D, Rodriguez Hermosillo, K, Ronenko, O, Rostowska, A, Rudko, L, Sakaan, F, Sakhar, N, Savva, N, Scaccaglia, D, Schaeffer, E, Schneider, C, Scobie, N, Semeniuk, O, Shevchyk, R, Shuler, A, Shvets, S, Skoczen, S, Smeal, W, Sokolowski, I, Sonkin, A, Stepanjuk, A, Spota, A, Sterba, J, Styczynski, J, Svintsova, O, Synyuta, A, Szczepanski, T, Szczucinski, P, Szmyd, B, Tasso Cereceda, M, Teliuk, A, Tomanek, I, Topping, P, Torrent, M, Trelinska, J, Troyanovska, O, Trubnikova, E, Tsurkan, L, Tsymbalyuk-Voloshyn, I, Urasinski, T, Urbanek-Dadela, A, Vasilieva, N, Vasilyeva, A, Verdu-Amoros, J, Vilcu-Bajurean, N, Vinitsky, L, Volpe, G, Vorobel, O, Wachowiak, J, Wasiak, M, Wiedower, L, Wuenschel, L, Wysocki, M, Yurieva, M, Zagurska, A, Zakharenko, S, Zakharenko, A, Zapotochna, K, Zawitkowska, J, Agulnik A., Kizyma R., Salek M., Wlodarski M. W., Pogorelyy M., Oszer A., Yakimkova T., Nogovitsyna Y., Dutkiewicz M., Dalle J. -H., Dirksen U., Eggert A., Fernandez-Teijeiro A., Greiner J., Kraal K., Mueller A., Sramkova L., Zecca M., Wise P. H., Mlynarski W., Avula M., Adyrov M. V., Berlanga P., Blackwood C. A., Bouffet E., Czauderna P. S., de Koning L. A., dos Reis Farinha N. J., Foster W. B., Graetz D. E., Gupta S., Holter W., Hough R. E., Kliuchkivska K., Kolenova A., Kolodrubiec J., Moreira D. C., Mukkada S. T., Mykychak I., Raciborska A., Salman Z. S., Sopilnyak A., Tyupa S., Vinitsky A., Wobst N. M., Miller B. A., Rasul S. S., Rodriguez-Galindo C., Alanbousi I., Alexander S. W., Apel A., Bal W. A., Balwierz W. A., Basset-Salom L., Bastardo Blanco D., Bauer K. J., Bayazitov I. T., Bhakta N. H., Bien E. I., Bieniek K. A., Blair S. J., Bodak K. I., Bordeianu I. M., Braganca J. M., Bucurenci M. S., Budny E. B., Budzyn A., Bumgardner C. C., Burditt R. N., Burnside Clapp V. G., Bykov V., Canete A., Carnelli M., Cela E., Cepowska Z. P., Chaber R., Cherner-Drieux A., Chubata M., Clough H. M., Czernicka - Siwecka J., Czyzewski K., Dashchakovska O., Dembowska-Baginska B. M., Derwich K., Dommett R., Dorosh O., Drabko K. A., Dragomir M. D., Dworzak M., Dyma S., Earl J. D., English M. W., Evseev D. A., Farren B. S., Fedyk N., Ferneza S., Fox Irwin L. E., Galazkowski R. M., Ganieva G., Garanzha V., Gelman M. S., Godzinski J. K., Goeres A. F., Golban R., Griksaitis M. J., Hampel M. A., Hastings S. G., Heenen D. L., Hill M. C., Holiuk I., Hutnik L. M., Irga-Jaworska N., Istomin O., Janczar S. L., Kacharian A., Kalwak K., Karolczyk G. M., Karpenko N. M., Katsubo H., Kaznowska B. J., Kentsis A., Ketteler P., Kienesberger A., Kiselev R., Kizyma Z., Klymniuk H., Kostiuk Y., Kowalik T., Kozlova O., Kozubenko V., Kramar T., Krawczuk-Rybak M., Kulemzina I., Kurkowska P., Kuzyk A. S., Ladenstein R. L., Laguna P. J., Lassaletta A., Lehmberg K., Leontieva O., Liashenko S., Loizou L. G., Lucchetta S. A., Lupo M. W., Lysytsia L., Lysytsia O., Machnik K. A., Mainland J. A., Matczak K. E., Matysiak M. J., Mayeur P., Minervina A. A., Mishkova V., Mizia-Malarz A. J., Morales La Madrid A., Moreno L., Moskvin V. P., Muszynska-Roslan K. M., Nelson A. J., Ociepa T., Oltolini S., Onipko N., Pappas A., Patel A. B., Patrahau A., Pauley J. L., Pavlenko Y., Pavlovych A., Peregud-Pogorzelski J., Perek-Polnik M., Perez V., Perez-Martinez A., Pikman Y., Pitozzi G., Portugal R. G., Posternak V. V., Prete A., Pritchard-Jones K., Radaelli A., Reeves T., Reinhardt D., Reshetnyak A. V., Rider A. J., Rizzari C., Rizzi D., Rodriguez Hermosillo K. G., Ronenko O., Rostowska A. O., Rudko L., Sakaan F. M., Sakhar N., Savva N. N., Scaccaglia D., Schaeffer E. H., Schneider C. U., Scobie N., Semeniuk O., Shevchyk R., Shuler A. I., Shvets S., Skoczen S. P., Smeal W. J., Sokolowski I., Sonkin A. A., Stepanjuk A. I., Spota A., Sterba J., Styczynski J., Svintsova O., Synyuta A. V., Szczepanski T., Szczucinski P. K., Szmyd B. M., Tasso Cereceda M., Teliuk A., Tomanek I., Topping P., Torrent M., Trelinska J., Troyanovska O., Trubnikova E., Tsurkan L. G., Tsymbalyuk-Voloshyn I., Urasinski T. F., Urbanek-Dadela A., Vasilieva N., Vasilyeva A., Verdu-Amoros J., Vilcu-Bajurean N., Vinitsky L., Volpe G., Vorobel O., Wachowiak J. T., Wasiak M. S., Wiedower L. A., Wuenschel L. I., Wysocki M. S., Yurieva M., Zagurska A., Zakharenko S. S., Zakharenko A. V., Zapotochna K., and Zawitkowska J. E.

Published
2022

12. Impact of Pre-Analytical and Analytical Variables Associated with Sample Preparation on Flow Cytometric Stainings Obtained with EuroFlow Panels

Author

Sedek, L, Flores-Montero, J, van der Sluijs, A, Kulis, J, Marvelde, J, Philippe, J, Bottcher, S, Bitter, M, Caetano, J, van der Velden, V, Sonneveld, E, Buracchi, C, Santos, A, Lima, M, Szczepanski, T, van Dongen, J, Orfao, A, Sedek L., Flores-Montero J., van der Sluijs A., Kulis J., Marvelde J. T., Philippe J., Bottcher S., Bitter M., Caetano J., van der Velden V. H. J., Sonneveld E., Buracchi C., Santos A. H., Lima M., Szczepanski T., van Dongen J. J. M., Orfao A., Sedek, L, Flores-Montero, J, van der Sluijs, A, Kulis, J, Marvelde, J, Philippe, J, Bottcher, S, Bitter, M, Caetano, J, van der Velden, V, Sonneveld, E, Buracchi, C, Santos, A, Lima, M, Szczepanski, T, van Dongen, J, Orfao, A, Sedek L., Flores-Montero J., van der Sluijs A., Kulis J., Marvelde J. T., Philippe J., Bottcher S., Bitter M., Caetano J., van der Velden V. H. J., Sonneveld E., Buracchi C., Santos A. H., Lima M., Szczepanski T., van Dongen J. J. M., and Orfao A.

Abstract

Objective interpretation of FC results may still be hampered by limited technical stan-dardization. The EuroFlow consortium conducted a series of experiments to determine the impact of different variables on the relative distribution and the median fluorescence intensity (MFI) of markers stained on different cell populations, from both healthy donors and patients’ samples with distinct hematological malignancies. The use of different anticoagulants; the time interval between sample collection, preparation, and acquisition; pH of washing buffers; and the use of cell surface membrane-only (SM) vs. cell surface plus intracytoplasmic (SM+CY) staining protocols, were evaluated. Our results showed that only monocytes were represented at higher percentages in EDTA-vs. heparin-anticoagulated samples. Application of SM or SM+CY protocols resulted in slight differences in the percentage of neutrophils and debris determined only with particular antibody combinations. In turn, storage of samples for 24 h at RT was associated with greater percentage of debris and cell doublets when the plasma cell disorder panel was used. Furthermore, 24 h storage of stained cells at RT was selectively detrimental for MFI levels of CD19 and CD45 on mature B-and T-cells (but not on leukemic blasts, clonal B-and plasma cells, neutrophils, and NK cells). The obtained results showed that the variables evaluated might need to be tailored for sample and cell type(s) as well as to the specific markers compared; however, defining of well-balanced boundaries for storage time, staining-to-acquisition delay, and pH of washing buffer would be a valid recommendation for most applications and circumstances described herein.

Published
2022

13. Flow cytometric minimal residual disease assessment in B-cell precursor acute lymphoblastic leukaemia patients treated with CD19-targeted therapies — a EuroFlow study

Author

Verbeek, M, Buracchi, C, Laqua, A, Nierkens, S, Sedek, L, Flores-Montero, J, Hofmans, M, Sobral de Costa, E, Novakova, M, Mejstrikova, E, Barrena, S, Kohlscheen, S, Szczepanowski, M, Kulis, J, Oliveira, E, Jugooa, R, de Jong, A, Szczepanski, T, Philippe, J, van Dongen, J, Orfao, A, Bruggemann, M, Gaipa, G, van der Velden, V, Verbeek M. W. C., Buracchi C., Laqua A., Nierkens S., Sedek L., Flores-Montero J., Hofmans M., Sobral de Costa E., Novakova M., Mejstrikova E., Barrena S., Kohlscheen S., Szczepanowski M., Kulis J., Oliveira E., Jugooa R., de Jong A. X., Szczepanski T., Philippe J., van Dongen J. J. M., Orfao A., Bruggemann M., Gaipa G., van der Velden V. H. J., Verbeek, M, Buracchi, C, Laqua, A, Nierkens, S, Sedek, L, Flores-Montero, J, Hofmans, M, Sobral de Costa, E, Novakova, M, Mejstrikova, E, Barrena, S, Kohlscheen, S, Szczepanowski, M, Kulis, J, Oliveira, E, Jugooa, R, de Jong, A, Szczepanski, T, Philippe, J, van Dongen, J, Orfao, A, Bruggemann, M, Gaipa, G, van der Velden, V, Verbeek M. W. C., Buracchi C., Laqua A., Nierkens S., Sedek L., Flores-Montero J., Hofmans M., Sobral de Costa E., Novakova M., Mejstrikova E., Barrena S., Kohlscheen S., Szczepanowski M., Kulis J., Oliveira E., Jugooa R., de Jong A. X., Szczepanski T., Philippe J., van Dongen J. J. M., Orfao A., Bruggemann M., Gaipa G., and van der Velden V. H. J.

Abstract

The standardized EuroFlow protocol, including CD19 as primary B-cell marker, enables highly sensitive and reliable minimal residual disease (MRD) assessment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients treated with chemotherapy. We developed and validated an alternative gating strategy allowing reliable MRD analysis in BCP-ALL patients treated with CD19-targeting therapies. Concordant data were obtained in 92% of targeted therapy patients who remained CD19-positive, whereas this was 81% in patients that became (partially) CD19-negative. Nevertheless, in both groups median MRD values showed excellent correlation with the original MRD data, indicating that, despite higher interlaboratory variation, the overall MRD analysis was correct.

Published
2022

14. Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated on the Interfant-06 protocol

Author

Stutterheim, J, de Lorenzo, P, van der Sluin, I, Alten, J, Ancliffe, P, Attarbaschi, A, Aversa, L, Boer, J, Biondi, A, Brethon, B, Diaz, P, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Leung, A, Locatelli, F, Silverman, L, Stary, J, Szczepanski, T, van der Velden, V, Vora, A, Zuna, J, Schrappe, M, Valsecchi, M, Pieters, R, Stutterheim J., de Lorenzo P., van der Sluin I. M., Alten J., Ancliffe P., Attarbaschi A., Aversa L., Boer J. M., Biondi A., Brethon B., Diaz P., Cazzaniga G., Escherich G., Ferster A., Kotecha R. S., Lausen B., Leung A. W., Locatelli F., Silverman L., Stary J., Szczepanski T., van der Velden V. H. J., Vora A., Zuna J., Schrappe M., Valsecchi M. G., Pieters R., Stutterheim, J, de Lorenzo, P, van der Sluin, I, Alten, J, Ancliffe, P, Attarbaschi, A, Aversa, L, Boer, J, Biondi, A, Brethon, B, Diaz, P, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Leung, A, Locatelli, F, Silverman, L, Stary, J, Szczepanski, T, van der Velden, V, Vora, A, Zuna, J, Schrappe, M, Valsecchi, M, Pieters, R, Stutterheim J., de Lorenzo P., van der Sluin I. M., Alten J., Ancliffe P., Attarbaschi A., Aversa L., Boer J. M., Biondi A., Brethon B., Diaz P., Cazzaniga G., Escherich G., Ferster A., Kotecha R. S., Lausen B., Leung A. W., Locatelli F., Silverman L., Stary J., Szczepanski T., van der Velden V. H. J., Vora A., Zuna J., Schrappe M., Valsecchi M. G., and Pieters R.

Abstract

Background: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study. Methods: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10−4), and high (≥5∗10−4). Results: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10−4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10−4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02). Conclusion: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.

Published
2022

15. First-Line Immunosuppressive Treatment in Children with Aplastic Anemia: Rabbit Antithymocyte Globulin

Author

Pawelec, K., Salamonowicz, M., Panasiuk, A., Demkow, U., Kowalczyk, J., Balwierz, W., Zaleska-Czepko, E., Chybicka, A., Szmyd, K., Szczepanski, T., Bubala, H., Wysocki, M., Kurylak, A., Wachowiak, J., Szpecht, D., Młynarski, W., Bulas, M., Krawczuk-Rybak, M., Leszczynska, E., Urasinski, T., Peregud-Pogorzelski, J., Balcerska, A., Kaczorowska-Hac, B., Matysiak, M., and Pokorski, Mieczyslaw, Series editor

Published
2015
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16. Phenotypic profiling of CD34+ cells by advanced flow cytometry improves diagnosis of Juvenile Myelomonocytic Leukemia

Author

Bugarin, C, Antolini, L, Buracchi, C, Matarraz, S, Coliva, T, Van der Velden, V, Szczepanski, T, Da Costa, E, Van der Sluijs, A, Novakova, M, Mejstrikova, E, Nierkens, S, De Mello, F, Fernandez, P, Aanei, C, Sędek, Ł, Strocchio, L, Masetti, R, Sainati, L, Philippé, J, Valsecchi, M, Locatelli, F, Van Dongen, J, Biondi, A, Orfao, A, Gaipa, G, Bugarin, Cristina, Antolini, Laura, Buracchi, Chiara, Matarraz, Sergio, Coliva, Tiziana Angela, Van der Velden, Vincent H, Szczepanski, Tomasz, Da Costa, Elaine Sobral, Van der Sluijs, Alita, Novakova, Michaela, Mejstrikova, Ester, Nierkens, Stefan, De Mello, Fabiana Vieira, Fernandez, Paula, Aanei, Carmen, Sędek, Łukasz, Strocchio, Luisa, Masetti, Riccardo, Sainati, Laura, Philippé, Jan, Valsecchi, Maria Grazia, Locatelli, Franco, Van Dongen, Jacques J M, Biondi, Andrea, Orfao, Alberto, Gaipa, Giuseppe, Bugarin, C, Antolini, L, Buracchi, C, Matarraz, S, Coliva, T, Van der Velden, V, Szczepanski, T, Da Costa, E, Van der Sluijs, A, Novakova, M, Mejstrikova, E, Nierkens, S, De Mello, F, Fernandez, P, Aanei, C, Sędek, Ł, Strocchio, L, Masetti, R, Sainati, L, Philippé, J, Valsecchi, M, Locatelli, F, Van Dongen, J, Biondi, A, Orfao, A, Gaipa, G, Bugarin, Cristina, Antolini, Laura, Buracchi, Chiara, Matarraz, Sergio, Coliva, Tiziana Angela, Van der Velden, Vincent H, Szczepanski, Tomasz, Da Costa, Elaine Sobral, Van der Sluijs, Alita, Novakova, Michaela, Mejstrikova, Ester, Nierkens, Stefan, De Mello, Fabiana Vieira, Fernandez, Paula, Aanei, Carmen, Sędek, Łukasz, Strocchio, Luisa, Masetti, Riccardo, Sainati, Laura, Philippé, Jan, Valsecchi, Maria Grazia, Locatelli, Franco, Van Dongen, Jacques J M, Biondi, Andrea, Orfao, Alberto, and Gaipa, Giuseppe

Abstract

Diagnostic criteria for juvenile myelomonocytic leukemia (JMML) are currently well defined, however in some patients diagnosis still remains a challenge. Flow cytometry is a well-established tool for diagnosis and follow-up of hematological malignancies, nevertheless it is not routinely used for JMML diagnosis. Herewith, we characterized the CD34+ hematopoietic precursor cells collected from 31 children with JMML using a combination of standardized EuroFlow antibody panels to assess the ability to discriminate JMML cells from normal/reactive bone marrow cell as controls (n=29) or from cells of children with other hematological diseases mimicking JMML (n=9). CD34+ precursors in JMML showed markedly reduced B and erythroid-committed precursors compared to controls, whereas monocytic and CD7+ lymphoid precursors were significantly expanded. Moreover, aberrant immunophenotypes were consistently present in CD34+ precursors in JMML, while they were virtually absent in controls. Multivariate logistic regression analysis showed that combined assessment of the number of CD34+CD7+ lymphoid precursors and CD34+ aberrant precursors or erythroid precursors had a great potential in discriminating JMMLs vs controls. Importantly our scoring model allowed highly efficient discrimination of truly JMML vs patients with JMML-like diseases. In conclusion, we show for the first time that CD34+ precursors from JMML patients display a unique immunophenotypic profile which might contribute to a fast and accurate diagnosis of JMML worldwide by applying an easy to standardize single 8-color antibody combination.

Published
2023

17. European standard clinical practice - Key issues for the medical care of individuals with familial leukemia

Author

Förster, A, Davenport, C, Duployez, N, Erlacher, M, Ferster, A, Fitzgibbon, J, Göhring, G, Hasle, H, Jongmans, M, Kolenova, A, Kronnie, G, Lammens, T, Mecucci, C, Mlynarski, W, Niemeyer, C, Sole, F, Szczepanski, T, Waanders, E, Biondi, A, Wlodarski, M, Schlegelberger, B, Ripperger, T, Förster, Alisa, Davenport, Claudia, Duployez, Nicolas, Erlacher, Miriam, Ferster, Alina, Fitzgibbon, Jude, Göhring, Gudrun, Hasle, Henrik, Jongmans, Marjolijn C, Kolenova, Alexandra, Kronnie, Geertruijte, Lammens, Tim, Mecucci, Cristina, Mlynarski, Wojciech, Niemeyer, Charlotte M, Sole, Francesc, Szczepanski, Tomasz, Waanders, Esmé, Biondi, Andrea, Wlodarski, Marcin, Schlegelberger, Brigitte, Ripperger, Tim, Förster, A, Davenport, C, Duployez, N, Erlacher, M, Ferster, A, Fitzgibbon, J, Göhring, G, Hasle, H, Jongmans, M, Kolenova, A, Kronnie, G, Lammens, T, Mecucci, C, Mlynarski, W, Niemeyer, C, Sole, F, Szczepanski, T, Waanders, E, Biondi, A, Wlodarski, M, Schlegelberger, B, Ripperger, T, Förster, Alisa, Davenport, Claudia, Duployez, Nicolas, Erlacher, Miriam, Ferster, Alina, Fitzgibbon, Jude, Göhring, Gudrun, Hasle, Henrik, Jongmans, Marjolijn C, Kolenova, Alexandra, Kronnie, Geertruijte, Lammens, Tim, Mecucci, Cristina, Mlynarski, Wojciech, Niemeyer, Charlotte M, Sole, Francesc, Szczepanski, Tomasz, Waanders, Esmé, Biondi, Andrea, Wlodarski, Marcin, Schlegelberger, Brigitte, and Ripperger, Tim

Abstract

Although hematologic malignancies (HM) are no longer considered exclusively sporadic, additional awareness of familial cases has yet to be created. Individuals carrying a (likely) pathogenic germline variant (e.g., in ETV6, GATA2, SAMD9, SAMD9L, or RUNX1) are at an increased risk for developing HM. Given the clinical and psychological impact associated with the diagnosis of a genetic predisposition to HM, it is of utmost importance to provide high-quality, standardized patient care. To address these issues and harmonize care across Europe, the Familial Leukemia Subnetwork within the ERN PaedCan has been assigned to draft an European Standard Clinical Practice (ESCP) document reflecting current best practices for pediatric patients and (healthy) relatives with (suspected) familial leukemia. The group was supported by members of the German network for rare diseases MyPred, of the Host Genome Working Group of SIOPE, and of the COST action LEGEND. The ESCP on familial leukemia is proposed by an interdisciplinary team of experts including hematologists, oncologists, and human geneticists. It is intended to provide general recommendations in areas where disease-specific recommendations do not yet exist. Here, we describe key issues for the medical care of familial leukemia that shall pave the way for a future consensus guideline: (i) identification of individuals with or suggestive of familial leukemia, (ii) genetic analysis and variant interpretation, (iii) genetic counseling and patient education, and (iv) surveillance and (psychological) support. To address the question on how to proceed with individuals suggestive of or at risk of familial leukemia, we developed an algorithm covering four different, partially linked clinical scenarios, and additionally a decision tree to guide clinicians in their considerations regarding familial leukemia in minors with HM. Our recommendations cover, not only patients but also relatives that both should have access to adequate medical

Published
2023

18. EBV-DRIVEN LYMPHOID NEOPLASMS ASSOCIATED WITH ALL MAINTENANCE THERAPY: AN INTERNATIONAL OBSERVATINAL STUDY

Author

Elitzur, S., primary, Vora, A., additional, Burkhardt, B., additional, Inaba, H., additional, Attarbaschi, A., additional, Baruchel, A., additional, Escherich, G., additional, Gibson, B., additional, Liu, H., additional, Loh, M., additional, Moorman, A., additional, Moricke, A., additional, Pieters, R., additional, Uyttebroeck, A., additional, Baird, S., additional, Bartram, J., additional, Ben-Harosh, M., additional, Bertrand, Y., additional, Buitenkamp, T., additional, Caldwell, K., additional, Drut, R., additional, Geerlinks, A., additional, Grainger, J., additional, Haouy, S., additional, Heaney, N., additional, Huang, M., additional, Ingham, D., additional, Krenova, Z., additional, Kuhlen, M., additional, Lehrnbecher, T., additional, Manabe, A., additional, Niggli, F., additional, Paris, C., additional, Revel-Vilk, S., additional, Rohrlich, P., additional, Sandeep, B., additional, Sinno, M., additional, Szczepanski, T., additional, Tamesberger, M., additional, Warrier, R., additional, Wolfl, M., additional, Nirel, R., additional, Izraeli, S., additional, Borkhardt, A., additional, and Schmiegelow, K., additional

Published
2022
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19. 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

20. 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

23. Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: an international collaborative study

Author

Boer, J M, van der Veer, A, Rizopoulos, D, Fiocco, M, Sonneveld, E, de Groot-Kruseman, H A, Kuiper, R P, Hoogerbrugge, P, Horstmann, M, Zaliova, M, Palmi, C, Trka, J, Fronkova, E, Emerenciano, M, do Socorro Pombo-de-Oliveira, M, Mlynarski, W, Szczepanski, T, Nebral, K, Attarbaschi, A, Venn, N, Sutton, R, Schwab, C J, Enshaei, A, Vora, A, Stanulla, M, Schrappe, M, Cazzaniga, G, Conter, V, Zimmermann, M, Moorman, A V, Pieters, R, and den Boer, M L

Published
2016
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24. Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated on the Interfant-06 protocol

Author

Stutterheim, J., de Lorenzo, P., van der Sluis, I. M., Alten, J., Ancliffe, P., Attarbaschi, A., Aversa, L., Boer, J. M., Biondi, A., Brethon, B., Diaz, P., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Leung, A. W., Locatelli, Franco, Silverman, L., Stary, J., Szczepanski, T., van der Velden, V. H. J., Vora, A., Zuna, J., Schrappe, M., Valsecchi, M. G., Pieters, R., Locatelli F. (ORCID:0000-0002-7976-3654), Stutterheim, J., de Lorenzo, P., van der Sluis, I. M., Alten, J., Ancliffe, P., Attarbaschi, A., Aversa, L., Boer, J. M., Biondi, A., Brethon, B., Diaz, P., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Leung, A. W., Locatelli, Franco, Silverman, L., Stary, J., Szczepanski, T., van der Velden, V. H. J., Vora, A., Zuna, J., Schrappe, M., Valsecchi, M. G., Pieters, R., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Background: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study. Methods: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10−4), and high (≥5∗10−4). Results: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10−4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10−4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02). Conclusion: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.

Published
2022

25. Flow cytometric minimal residual disease assessment in B-cell precursor acute lymphoblastic leukaemia patients treated with CD19-targeted therapies — a EuroFlow study

Author

Verbeek, M. W. C., Buracchi, C., Laqua, A., Nierkens, S., Sedek, L., Flores-Montero, J., Hofmans, M., Sobral de Costa, E., Nováková, M., Mejstrikova, E., Barrena, S., Kohlscheen, S., Szczepanowski, M., Kulis, J., Oliveira, E., Jugooa, R., de Jong, A. X., Szczepanski, T., Philippé, J., van Dongen, J. J. M., Orfao, A., Brüggemann, M., Gaipa, G., van der Velden, V. H. J., Verbeek, M. W. C., Buracchi, C., Laqua, A., Nierkens, S., Sedek, L., Flores-Montero, J., Hofmans, M., Sobral de Costa, E., Nováková, M., Mejstrikova, E., Barrena, S., Kohlscheen, S., Szczepanowski, M., Kulis, J., Oliveira, E., Jugooa, R., de Jong, A. X., Szczepanski, T., Philippé, J., van Dongen, J. J. M., Orfao, A., Brüggemann, M., Gaipa, G., and van der Velden, V. H. J.

Abstract

The standardized EuroFlow protocol, including CD19 as primary B-cell marker, enables highly sensitive and reliable minimal residual disease (MRD) assessment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients treated with chemotherapy. We developed and validated an alternative gating strategy allowing reliable MRD analysis in BCP-ALL patients treated with CD19-targeting therapies. Concordant data were obtained in 92% of targeted therapy patients who remained CD19-positive, whereas this was 81% in patients that became (partially) CD19-negative. Nevertheless, in both groups median MRD values showed excellent correlation with the original MRD data, indicating that, despite higher interlaboratory variation, the overall MRD analysis was correct.

Published
2022

26. Bone Marrow Stromal Cell Regeneration Profile in Treated B-Cell Precursor Acute Lymphoblastic Leukemia Patients: Association with MRD Status and Patient Outcome

Author

Oliveira, E, Costa, E, Ciudad, J, Gaipa, G, Sedek, Ł, Barrena, S, Szczepanski, T, Buracchi, C, Silvestri, D, Siqueira, P, Mello, F, Torres, R, Oliveira, L, Fay-Neves, I, Sonneveld, E, van der Velden, V, Mejstrikova, E, Ribera, J, Conter, V, Schrappe, M, van Dongen, J, Land, M, Orfao, A, Oliveira, E, Costa, E, Ciudad, J, Gaipa, G, Sedek, Ł, Barrena, S, Szczepanski, T, Buracchi, C, Silvestri, D, Siqueira, P, Mello, F, Torres, R, Oliveira, L, Fay-Neves, I, Sonneveld, E, van der Velden, V, Mejstrikova, E, Ribera, J, Conter, V, Schrappe, M, van Dongen, J, Land, M, and Orfao, A

Abstract

For the last two decades, measurable residual disease (MRD) has become one of the most powerful independent prognostic factors in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the effect of therapy on the bone marrow (BM) microenvironment and its potential relationship with the MRD status and disease free survival (DFS) still remain to be investigated. Here we analyzed the distribution of mesenchymal stem cells (MSC) and endothelial cells (EC) in the BM of treated BCP-ALL patients, and its relationship with the BM MRD status and patient outcome. For this purpose, the BM MRD status and EC/MSC regeneration profile were analyzed by multiparameter flow cytometry (MFC) in 16 control BM (10 children; 6 adults) and 1204 BM samples from 347 children and 100 adult BCP-ALL patients studied at diagnosis (129 children; 100 adults) and follow-up (824 childhood samples; 151 adult samples). Patients were grouped into a discovery cohort (116 pediatric BCP-ALL patients; 338 samples) and two validation cohorts (74 pediatric BCP-ALL, 211 samples; and 74 adult BCP-ALL patients; 134 samples). Stromal cells (i.e., EC and MSC) were detected at relatively low frequencies in all control BM (16/16; 100%) and in most BCP-ALL follow-up samples (874/975; 90%), while they were undetected in BCP-ALL BM at diagnosis. In control BM samples, the overall percentage of EC plus MSC was higher in children than adults (p = 0.011), but with a similar EC/MSC ratio in both groups. According to the MRD status similar frequencies of both types of BM stromal cells were detected in BCP-ALL BM studied at different time points during the follow-up. Univariate analysis (including all relevant prognostic factors together with the percentage of stromal cells) performed in the discovery cohort was used to select covariates for a multivariate Cox regression model for predicting patient DFS. Of note, an increased percentage of EC (>32%) within the BCP-ALL BM stromal cell compartment at day +78 of

Published
2022

27. Unusual Immunoglobulin and T-cell Receptor Gene Rearrangement Patterns in Acute Lymphoblastic Leukemias

Author

Szczepański, T., Pongers-Willemse, M. J., Langerak, A. W., van Dongen, J. J. M., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Koprowski, H., editor, Ito, Y., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Melchers, Fritz, editor, and Potter, Michael, editor

Published
1999
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29. Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated on the Interfant-06 protocol

Author

Stutterheim, J., primary, de Lorenzo, P., additional, van der Sluis, I.M., additional, Alten, J., additional, Ancliffe, P., additional, Attarbaschi, A., additional, Aversa, L., additional, Boer, J.M., additional, Biondi, A., additional, Brethon, B., additional, Diaz, P., additional, Cazzaniga, G., additional, Escherich, G., additional, Ferster, A., additional, Kotecha, R.S., additional, Lausen, B., additional, Leung, Alex WK., additional, Locatelli, F., additional, Silverman, L., additional, Stary, J., additional, Szczepanski, T., additional, van der Velden, V.H.J., additional, Vora, A., additional, Zuna, J., additional, Schrappe, M., additional, Valsecchi, M.G., additional, and Pieters, R., additional

Published
2022
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30. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol: Results from an international phase III randomized study

Author

Pieters, R, De Lorenzo, P, Ancliffe, P, Aversa, L, Brethon, B, Biondi, A, Campbell, M, Escherich, G, Ferster, A, Gardner, R, Kotecha, R, Lausen, B, Li, C, Locatelli, F, Attarbaschi, A, Peters, C, Rubnitz, J, Silverman, L, Stary, J, Szczepanski, T, Vora, A, Schrappe, M, Valsecchi, M, Pieters R., De Lorenzo P., Ancliffe P., Aversa L. A., Brethon B., Biondi A., Campbell M., Escherich G., Ferster A., Gardner R. A., Kotecha R. S., Lausen B., Li C. K., Locatelli F., Attarbaschi A., Peters C., Rubnitz J. E., Silverman L. B., Stary J., Szczepanski T., Vora A., Schrappe M., Valsecchi M. G., Pieters, R, De Lorenzo, P, Ancliffe, P, Aversa, L, Brethon, B, Biondi, A, Campbell, M, Escherich, G, Ferster, A, Gardner, R, Kotecha, R, Lausen, B, Li, C, Locatelli, F, Attarbaschi, A, Peters, C, Rubnitz, J, Silverman, L, Stary, J, Szczepanski, T, Vora, A, Schrappe, M, Valsecchi, M, Pieters R., De Lorenzo P., Ancliffe P., Aversa L. A., Brethon B., Biondi A., Campbell M., Escherich G., Ferster A., Gardner R. A., Kotecha R. S., Lausen B., Li C. K., Locatelli F., Attarbaschi A., Peters C., Rubnitz J. E., Silverman L. B., Stary J., Szczepanski T., Vora A., Schrappe M., and Valsecchi M. G.

Abstract

PURPOSE Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stemcell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 3 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE1MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant- 06 did not improve compared with that in Interfant-99.

Published
2019

33. Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study

Author

Styczynski, J., Czyzewski, K., Wysocki, M., Gryniewicz-Kwiatkowska, O., Kolodziejczyk-Gietka, A., Salamonowicz, M., Hutnik, L., Zajac-Spychala, O., Zaucha-Prazmo, A., Chelmecka-Wiktorczyk, L., Siewiera, K., Fraczkiewicz, J., Malas, Z., Tomaszewska, R., Irga-Jaworska, N., Plonowski, M., Ociepa, T., Pierlejewski, F., Gamrot, Z., Urbanek-Dadela, A., Gozdzik, J., Stolpa, W., Dembowska-Baginska, B., Perek, D., Matysiak, M., Wachowiak, J., Kowalczyk, J., Balwierz, W., Kalwak, K., Chybicka, A., Badowska, W., Szczepanski, T., Drozynska, E., Krawczuk-Rybak, M., Urasinski, T., Mlynarski, W., Woszczyk, M., Karolczyk, G., Sobol-Milejska, G., and Gil, L.

Published
2016
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34. First-Line Immunosuppressive Treatment in Children with Aplastic Anemia: Rabbit Antithymocyte Globulin

Author

Pawelec, K., primary, Salamonowicz, M., additional, Panasiuk, A., additional, Demkow, U., additional, Kowalczyk, J., additional, Balwierz, W., additional, Zaleska-Czepko, E., additional, Chybicka, A., additional, Szmyd, K., additional, Szczepanski, T., additional, Bubala, H., additional, Wysocki, M., additional, Kurylak, A., additional, Wachowiak, J., additional, Szpecht, D., additional, Młynarski, W., additional, Bulas, M., additional, Krawczuk-Rybak, M., additional, Leszczynska, E., additional, Urasinski, T., additional, Peregud-Pogorzelski, J., additional, Balcerska, A., additional, Kaczorowska-Hac, B., additional, and Matysiak, M., additional

Published
2014
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35. Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

Author

Stutterheim, J., van der Sluis, I. M., de Lorenzo, P., Alten, J., Ancliffe, P., Attarbaschi, A., Brethon, B., Biondi, A., Campbell, M., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Li, C. K., Lo Nigro, L., Locatelli, Franco, Marschalek, R., Meyer, C., Schrappe, M., Stary, J., Vora, A., Zuna, J., van der Velden, V. H. J., Szczepanski, T., Valsecchi, M. G., Pieters, R., Locatelli F. (ORCID:0000-0002-7976-3654), Stutterheim, J., van der Sluis, I. M., de Lorenzo, P., Alten, J., Ancliffe, P., Attarbaschi, A., Brethon, B., Biondi, A., Campbell, M., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Li, C. K., Lo Nigro, L., Locatelli, Franco, Marschalek, R., Meyer, C., Schrappe, M., Stary, J., Vora, A., Zuna, J., van der Velden, V. H. J., Szczepanski, T., Valsecchi, M. G., Pieters, R., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

PURPOSE: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). MATERIALS AND METHODS: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4). RESULTS: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9). CONCLUSION: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may bene

Published
2021

36. Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

Author

Stutterheim, J, van der Sluis, I, de Lorenzo, P, Alten, J, Ancliffe, P, Attarbaschi, A, Brethon, B, Biondi, A, Campbell, M, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Li, C, Lo Nigro, L, Locatelli, F, Marschalek, R, Meyer, C, Schrappe, M, Stary, J, Vora, A, Zuna, J, van der Velden, V, Szczepanski, T, Valsecchi, M, Pieters, R, Stutterheim, Janine, van der Sluis, Inge M, de Lorenzo, Paola, Alten, Julia, Ancliffe, Philip, Attarbaschi, Andishe, Brethon, Benoit, Biondi, Andrea, Campbell, Myriam, Cazzaniga, Giovanni, Escherich, Gabriele, Ferster, Alina, Kotecha, Rishi S, Lausen, Birgitte, Li, Chi Kong, Lo Nigro, Luca, Locatelli, Franco, Marschalek, Rolf, Meyer, Claus, Schrappe, Martin, Stary, Jan, Vora, Ajay, Zuna, Jan, van der Velden, Vincent H J, Szczepanski, Tomasz, Valsecchi, Maria Grazia, Pieters, Rob, Stutterheim, J, van der Sluis, I, de Lorenzo, P, Alten, J, Ancliffe, P, Attarbaschi, A, Brethon, B, Biondi, A, Campbell, M, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Li, C, Lo Nigro, L, Locatelli, F, Marschalek, R, Meyer, C, Schrappe, M, Stary, J, Vora, A, Zuna, J, van der Velden, V, Szczepanski, T, Valsecchi, M, Pieters, R, Stutterheim, Janine, van der Sluis, Inge M, de Lorenzo, Paola, Alten, Julia, Ancliffe, Philip, Attarbaschi, Andishe, Brethon, Benoit, Biondi, Andrea, Campbell, Myriam, Cazzaniga, Giovanni, Escherich, Gabriele, Ferster, Alina, Kotecha, Rishi S, Lausen, Birgitte, Li, Chi Kong, Lo Nigro, Luca, Locatelli, Franco, Marschalek, Rolf, Meyer, Claus, Schrappe, Martin, Stary, Jan, Vora, Ajay, Zuna, Jan, van der Velden, Vincent H J, Szczepanski, Tomasz, Valsecchi, Maria Grazia, and Pieters, Rob

Abstract

Purpose: Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). Materials and methods: MRD was measured in 249 infants by DNA-based polymerase chain reaction of rearranged KMT2A, immunoglobulin, and/or T-cell receptor genes, at the end of induction (EOI) and end of consolidation (EOC). MRD results were classified as negative, intermediate (< 5 × 10-4), and high (≥ 5 × 10-4). Results: EOI MRD levels predicted outcome with 6-year disease-free survival (DFS) of 60.2% (95% CI, 43.2 to 73.6), 45.0% (95% CI, 28.3 to 53.1), and 33.8% (95% CI, 23.8 to 44.1) for infants with negative, intermediate, and high EOI MRD levels, respectively (P = .0039). EOC MRD levels were also predictive of outcome, with 6-year DFS of 68.2% (95% CI, 55.2 to 78.1), 40.1% (95% CI, 28.1 to 51.9), and 11.9% (95% CI, 2.6 to 29.1) for infants with negative, intermediate, and high EOC MRD levels, respectively (P < .0001). Analysis of EOI MRD according to the type of consolidation treatment showed that infants treated with lymphoid-style consolidation had 6-year DFS of 78.2% (95% CI, 51.4 to 91.3), 47.2% (95% CI, 33.0 to 60.1), and 23.2% (95% CI, 12.1 to 36.4) for negative, intermediate, and high MRD levels, respectively (P < .0001), while for myeloid-style-treated patients the corresponding figures were 45.0% (95% CI, 23.9 to 64.1), 41.3% (95% CI, 23.2 to 58.5), and 45.9% (95% CI, 29.4 to 60.9). Conclusion: This study provides support for the idea that induction therapy selects patients for subsequent therapy; infants with high EOI MRD may benefit from AML-like consolidation (DFS 45.9% v 23.2%), whereas patients with low EOI MRD may bene

Published
2021

38. New insights to the MLL recombinome of acute leukemias

Author

Meyer, C, Kowarz, E, Hofmann, J, Renneville, A, Zuna, J, Trka, J, Ben Abdelali, R, Macintyre, E, De Braekeleer, E, De Braekeleer, M, Delabesse, E, de Oliveira, M P, Cavé, H, Clappier, E, van Dongen, J J M, Balgobind, B V, van den Heuvel-Eibrink, M M, Beverloo, H B, Panzer-Grümayer, R, Teigler-Schlegel, A, Harbott, J, Kjeldsen, E, Schnittger, S, Koehl, U, Gruhn, B, Heidenreich, O, Chan, L C, Yip, S F, Krzywinski, M, Eckert, C, Möricke, A, Schrappe, M, Alonso, C N, Schäfer, B W, Krauter, J, Lee, D A, zur Stadt, U, Te Kronnie, G, Sutton, R, Izraeli, S, Trakhtenbrot, L, Lo Nigro, L, Tsaur, G, Fechina, L, Szczepanski, T, Strehl, S, Ilencikova, D, Molkentin, M, Burmeister, T, Dingermann, T, Klingebiel, T, and Marschalek, R

Published
2009
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39. 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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40. Standardised immunophenotypic analysis of myeloperoxidase in acute leukaemia

Author

Bras, A.E. (Anne), Osmani, Z. (Zgjim), Haas, V. (Valerie) de, Jongen-Lavrencic, M. (Mojca), Marvelde, J.G. (Jeroen) te, Zwaan, C.M. (Michel), Mejstříková, E. (Ester), Fernandez, P. (Paula), Szczepanski, T. (Tomasz), Orfao, A. (Alberto), van Dongen, J.J.M. (Jacques J. M.), Velden, V.H.J. (Vincent) van der, Bras, A.E. (Anne), Osmani, Z. (Zgjim), Haas, V. (Valerie) de, Jongen-Lavrencic, M. (Mojca), Marvelde, J.G. (Jeroen) te, Zwaan, C.M. (Michel), Mejstříková, E. (Ester), Fernandez, P. (Paula), Szczepanski, T. (Tomasz), Orfao, A. (Alberto), van Dongen, J.J.M. (Jacques J. M.), and Velden, V.H.J. (Vincent) van der

Abstract

Given its myeloid-restricted expression, myeloperoxidase (MPO) is typically used for lineage assignment (myeloid vs. lymphoid) during acute leukaemia (AL) diagnostics. In the present study, a robust flow cytometric definition for MPO positivity was established based on the standardised EuroFlow protocols, the standardised Acute Leukaemia Orientation Tube and 1734 multicentre AL cases (with confirmed assay stability). The best diagnostic performance was achieved by defining MPO positivity as ≥20% of the AL cells exceeding a lymphocyte-based threshold. The methodology employed should be applicable to any form of standardised flow cytometry.

Published
2020
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41. 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

48. 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

49. 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

50. Erratum: Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant-99 protocol (Leukemia (2016) 30 5 (1184-1187))

Author

Driessen E. M. C., Driessen, E, de Lorenzo, P, Campbell, M, Felice, M, Ferster, A, Hann, I, Vora, A, Hovi, L, Escherich, G, Li, C, Mann, G, Leblanc, T, Locatelli, F, Biondi, A, Rubnitz, J, Schrappe, M, Silverman, L, Stary, J, Suppiah, R, Szczepanski, T, Valsecchi, M, Pieters, R, Driessen E. M. C., de Lorenzo P., Campbell M., Felice M., Ferster A., Hann I., Vora A., Hovi L., Escherich G., Li C. K., Mann G., Leblanc T., Locatelli F., Biondi A., Rubnitz J., Schrappe M., Silverman L., Stary J., Suppiah R., Szczepanski T., Valsecchi M., Pieters R., Driessen E. M. C., Driessen, E, de Lorenzo, P, Campbell, M, Felice, M, Ferster, A, Hann, I, Vora, A, Hovi, L, Escherich, G, Li, C, Mann, G, Leblanc, T, Locatelli, F, Biondi, A, Rubnitz, J, Schrappe, M, Silverman, L, Stary, J, Suppiah, R, Szczepanski, T, Valsecchi, M, Pieters, R, Driessen E. M. C., de Lorenzo P., Campbell M., Felice M., Ferster A., Hann I., Vora A., Hovi L., Escherich G., Li C. K., Mann G., Leblanc T., Locatelli F., Biondi A., Rubnitz J., Schrappe M., Silverman L., Stary J., Suppiah R., Szczepanski T., Valsecchi M., and Pieters R.

Abstract

This corrects the article DOI: 10.1038/leu.2015.246.

Published
2017

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