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1. IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen

Author

Marta Libura, Emilia Bialopiotrowicz, Sebastian Giebel, Agnieszka Wierzbowska, Gail J. Roboz, Beata Piatkowska-Jakubas, Marta Pawelczyk, Patryk Gorniak, Katarzyna Borg, Magdalena Wojtas, Izabella Florek, Karolina Matiakowska, Bozena Jazwiec, Iwona Solarska, Monika Noyszewska-Kania, Karolina Piechna, Magdalena Zawada, Sylwia Czekalska, Zoriana Salamanczuk, Karolina Karabin, Katarzyna Wasilewska, Monika Paluszewska, Elzbieta Urbanowska, Justyna Gajkowska-Kulik, Grazyna Semenczuk, Justyna Rybka, Tomasz Wrobel, Anna Ejduk, Dariusz Kata, Sebastian Grosicki, Tadeusz Robak, Agnieszka Pluta, Agata Kominek, Katarzyna Piwocka, Karolina Pyziak, Agnieszka Sroka-Porada, Anna Wrobel, Agnieszka Przybylowicz, Marzena Wojtaszewska, Krzysztof Lewandowski, Lidia Gil, Agnieszka Piekarska, Wanda Knopinska, Lukasz Bolkun, Krzysztof Warzocha, Kazimierz Kuliczkowski, Tomasz Sacha, Grzegorz Basak, Wieslaw Wiktor Jedrzejczak, Jerzy Holowiecki, Przemysław Juszczynski, and Olga Haus

Subjects
Medicine, Science
Abstract

Abstract Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) genes occur in about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation and epigenetic deregulation. We assessed the prognostic significance of IDH1/2 mutations (IDH1/2 +) in 398 AML patients with normal karyotype (NK-AML), treated with daunorubicine + cytarabine (DA), DA + cladribine (DAC), or DA + fludarabine. IDH2 mutation was an independent favorable prognostic factor for 4-year overall survival (OS) in total NK-AML population (p = 0.03, censoring at allotransplant). We next evaluated the effect of addition of cladribine to induction regimen on the patients’ outcome according to IDH1/2 mutation status. In DAC group, 4-year OS was increased in IDH2 + patients, compared to IDH-wild type group (54% vs 33%; p = 0.0087, censoring at allotransplant), while no difference was observed for DA-treated subjects. In multivariate analysis, DAC independently improved the survival of IDH2 + patients (HR = 0.6 [0.37–0.93]; p = 0.024; censored at transplant), indicating that this group specifically benefits from cladribine-containing therapy. In AML cells with R140Q or R172K IDH2 mutations, cladribine restrained mutations-related DNA hypermethylation. Altogether, DAC regimen produces better outcomes in IDH2 + NK-AML patients than DA, and this likely results from the hypomethylating activity of cladribine. Our observations warrant further investigations of induction protocols combining cladribine with IDH1/2 inhibitors in IDH2-mutant.

Published
2021
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2. Data-driven flow cytometry classification of blast differentiation in older patients with acute myeloid leukemia

Author

Rojas, F., Longoni, H., Milone, G., Fernández, I., Conciencia, Clínica, Ramirez, R., Canepa, C., Saba, S., Balladares, G., Ventiurini, C., Mariano, R., Negri, P., Prates, M.V., Milone, J., Fazio, P., Gelemur, M., Ciarlo, S., Bezares, F., López, L., García, J. J, Giunta, M., Kruss, M., Lafalse, D., Marquesoni, E., Casale, M.F., Gimenez, A., Brulc, E.B., Perusini, M.A., Palmer, L., Correa, M.E., Jaramillo, F.J., Rosales, J., Sossa, C., Herrera, J.C., Arango, M., Holojda, J., Golos, A., Ejduk, A., Ochrem, B., Małgorzata, G., Waszczuk-Gajda, A., Drozd-Sokolowska, J., Czemerska, M., Paluszewska, M., Zarzycka, E., Masternak, A., Hawrylecka, Dr., Podhoreka, M., Giannopoulos, K., Gromek, T., Oleksiuk, J., Armatys, bA., Helbig, G., Sobas, M., Szczepaniak, A., Rzenno, E., Rodzaj, M., Piatkowska-Jakubas, B., Skret, A., Pluta, A., Barańska, E., Vasconcelos, G., Brioso, J., Nunes, A., Bogalho, I., Espadana, A., Coucelo, M., Marini, S., Azevedo, J., Crisostomo, A.I., Ribeiro, L., Pereira, V., Botelho, A., Mariz, J.M., Guimaraes, J.E., Aguiar, E., Coutinho, J., Noriega, V., García, L., Varela, C., Debén, G., González, M.R., Encinas, M., Bendaña, A., González, S., Bello, J.L., Albors, M., Algarra, L., Romero, J.R., Bermon, J.S., Varo, M.J., López, V., López, E., Mora, C., Amorós, C., Romero, A., Jaramillo, A., Valdez, N., Molina, I., Fernández, A., Sánchez, B., García, A., Castaño, V., López, T., Bernabeu, J., Sánchez, M.J., Fernández, C., Gil, C., Botella, C., Fernández, P., Pacheco, M., Tarín, F., Verdú, J.J., García, M.J., Mellado, A., García, M.C., González, J., Castillo, T., Colado, E., Alonso, S., Recio, I., Cabezudo, M., Davila, J., Rodríguez, M.J., Barez, A., Díaz, B., Prieto, J., Arnan, M., Marín, C., Mansilla, M., Balaberdi, A., Amutio, M.E., del Orbe, R.A., Ancin, I., Ruíz, J.C., Olivalres, M., Gómez, C., gonzález, I., Celis, M., Atutxa, K., Carrascosa, T., Artola, T., Lizuain, M., Rodriguez, J .I., Arce, O., Márquez, J.A., Atuch, J., Marco de Lucas, F., Díez, Z., Dávila, B., Cantalejo, R., Díaz, M., Labrador, J., Serra, F., Hermida, G., Díaz, F.J., de Vicente, P., Álvarez, R., Alonso, C., Bergua, J.M., Ugalde, N., Pardal, E., Saldaña, R., Rodríguez, F., Martín, E., Hermosín, L., Garrastazul, M.P., Marchante, I., Raposo, J.A., Capote, F.J., Colorado, M., Batlle, A., Yañez, L., García, S., González, P., Ocio, E.M., Briz, M., Bermúdez, A., Jiménez, C., Beltrán, S., Montagud, M., Castillo, I., García, R., Gascón, A., Clavel, J., Lancharro, A., Lnares, L., Herráez, M.M., Milena, A., Romero, M.J., Hernández, B., Calle, C., Benegas, R., Bolívar, Dr., Serrano, J., Dorado, F.J., Sánchez, J., Martínez, M.C., Cerveró, C.J., Busto, M.J., Bernal, M., Moratalla, L., Mesa, Z., Jurado, M., De Miguel, D., Santos, A.B., Arbeteta, J., Pérez, E., Caminos, N., Uresandi, N., Argoitiaituart, N., Swen, J., Uranga, A., Olazaba, I., Gainza, E., Romero, P., Gil, E., Palma, A.J., Gómez, K.G., Solé, M., Rodríguez, J.N., Murillo, I.M., Marco, J., Serena, J., Marco, V., Perella, M., Costilla, L., López, J.A., Baena, A., Almagro, P., Hermosilla, M., Esteban, A., Campeny, B.A., Nájera, M.J., Herrra, P., Fernández, R., González, J.D., Torres, L., Jiménez, S., Gómez, M.T., Bilbao, C., Rodríguez, C., Hong, A., Ramos de Laón, Y., Afonso, V., Ramos, F., Fuertes, M., de Cabo, E., Aguilera, C., Megido, M., García, T., Lavilla, E., Varela, M., Ferrero, S., Arias, J., Vizcaya, L., Roldán, A., Vilches, A., Penalva, M.J., Vázquez, J., Calderón, M.T., Matilla, A., Serí, C., Otero, M.J., García, N., Sandoval, E., Franco, C., Flores, R., Bravo, P., López, A., López, J.L., Blas, C., Díez, A., Alonso, J.M., Soto, C., Arenas, A., García, J., Martín, Y., Villafuerte, P.S., Magro, E., Bautista, G., De Laiglesia, A., Rodríguez, G., Solán, L., Chicano, M., Balsalobre, P., Monsalvo, S., Font, P., Carbonell, D., Martínez, C., Humala, K., Kerguelen, A.E., Hernández, D., Gasior, M., Gómez, P., Sánchez, I., Redondo, S., Llorente, L., Bengochea, M., Pérez, J., Sebrango, A., M. santero, Morales, A., Figuera, A., Villafuerte, P., Alegre, A., Fernández, E., Alonso, A., Martínez, M.P., Martínez, J., Cedena, M.T., Moreno, L., De la Fuente, A., García, D., Chamorro, C., Pradillo, V., Martí, E., Sánchez, J.M., Delgado, I., Rosado, B., Velasco, A., Miranda, C., Salvatierra, G., Foncillas, M., Hernández, J.A., Escolano, C., Benabente, C., Martínez, R., Polo, M., Anguita, E., Riaza, R., Amores, G., Requena, M.J., Javier, F., Villaloón, L., Aláez, C., Nistal, S., Navas, B., Andreu, M.A., Herrera, P., López, J., García, M., Moreno, M.J., Queipo, M.P., Hernández, A., Barrios, M., Heiniger, A., Jiménez, A., Contento, A., López, F., Alcalá, M., Lorente, S., González, M., Morales, E.M., Gutierrez, J., Serna, M.J., Beltrán, V., Romera, M., Berenguer, M., MArtínez, A., Tejedor, A., Amigo, M.L., Ortuño, F., Jerez, A., López, O., Moraleda, J.M., Rosique, P., Gómez, J., Garay, M.C., Cerezuela, P., MArtínez, A.B., González, A., Ibáñez, J., Alfaro, M.J., Mateos, M., Goñi, M.A., Araiz, M.A., Gorosquieta, A., Zudaire, M., Viguria, M., Zabala, A., Alvarellos, M., Quispe, I., Sánchez, M.P., Hurtado, G., Pérez, M., Burguete, Y., Areizaga, N., Galicia, T., Rifón, J., Alfonso, A., Prósper, F., Marcos, M., Tamariz, L.E., Riego, V., Manubens, A., Larrayoz, M.J., Calasanz, M.J., Mañú, A., Paiva, B., Vázquez, I., Burgos, L., Pereiro, M., Rodríguez, M., Pastoriza, M.C., Mendez, J.A., Sastre, J.L., Iglesias, M., Ulibarrena, C., Campoy, F., Jaimes, D., Albarrán, B., Solano, J., Silvestre, A., Albo, C., Suarez, S., Loureiro, C., Figueroa, I., Fernández, M.A., Martínez, A., Poderós, C., Vazquez, J., Iglesias, L., Nieto, A., Torrado, T., Martínez, A.M., Amador, M.L., Oubiña, P., Feijó, E., Dios, A., Loyola, I., Roreno, R., Simiele, A., Álvarez, L., Turcu, V., Vidriales, B., Avendaño, A., Chillón, C., González, V., Govantes, J.V., Rubio, S., Tapia, M., Olivier, C., Queizán, J.A., Pérez, O., Vera, J.A., Muñoz, C., rodriguez, A., González, N., Pérez, J.A., Soria, E., I.Espigado, Falantes, J., Montero, I., García, P., Rodríguez, E., Carrillo, E., Caballero, T., García, C., Couto, C., Simón, I., Gómez, M., Aguilar, C., González, B.J., Lakhwani, S., Bienert, A., González, B., Cabello, A., Oliva, A.Y., González, H., Sancho, L., Paricio, M., Perdiguer, L., Solano, F., Lerma, A., Martínez, M.D., Gómez, M.I., Yeguas, A., Montesinos, P., Barragán, E., Sargas, C., Amigo, R., Martinez, D., Boluda, B., Rodríguez, R., Acuña, E., Cano, I., Escrivá, A., Pedreño, M., Navalón, A., Orts, M., Sayas, M.J., Fernández, M.J., Juan, M.L., Gómez, E., Gimeno, M., Donato, E., Cejalvo, M., Tormo, M., Calabuig, M., Navarro, B., Martin, I., Villamont, E., Miralles, A., Lluch, R., Moragues, M., Ruiz, M.A., Benet, C., Valero, M., Linares, M., Collado, R., Orero, M., Ibañez, P., Lis, M.J., Pérez, P.L., Roig, M., López, M., Mena, A.V., Picón, I., Cánovas, V., Palacios, A., Cuello, R., Borrego, J., burgois, M., Cantalapiedra, A., Norberto, O., Angomas, E., Cidoncha, B., Cuevas, L., Robles, D., Mendiazabal, A., Oiartzabal, I., Guinea de Castro, J.M., Montes, C., Carrasco, V., Pérez, A., Moneva, J.J., Olave, M., Bonafonte, E., Mayor, L., Azaceta, G., Palomera, L., Malo, M., Escobar, M.J., Grasa, J.M., De Rueda, B., Aulés, A., Salvador, C., Ansó, V., Iborra, A., Delagado, P., Rubio, A., Stevenazzi, M., Alpire, I., Irigoin, V., Díaz, L., Guillermo, C., Guadagna, R., Grille, S., Oliver, C., Boada, M., Vales, V., Prado, A.I., De los Santos, A.P., Simoes, Catia, Gonzalez, Carmen, Vergez, François, Sarry, Audrey, Bertoli, Sarah, Ariceta, Beñat, Martínez-Cuadrón, David, Bergua, Juan-Miguel, Vives, Susana, Algarra, Lorenzo, Tormo, Mar, Martinez, Pilar, Serrano, Josefina, Herrera, Pilar, Ramos, Fernando, Salamero, Olga, Lavilla, Esperanza, Gil, Cristina, Lopez-Lorenzo, Jose-Luis, Vidriales, Maria-Belen, Chillon, Carmen, Labrador, Jorge, Falantes, Jose-Francisco, Sayas, María-José, Ayala, Rosa, Martinez-Lopez, Joaquin, Villar, Sara, Calasanz, Maria-Jose, Prosper, Felipe, San-Miguel, Jesús F., Sanz, Miguel Á., Récher, Christian, Paiva, Bruno, and Montesinos, Pau

Published
2024
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3. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study

Author

Kantarjian, Hagop M, DeAngelo, Daniel J, Advani, Anjali S, Stelljes, Matthias, Kebriaei, Partow, Cassaday, Ryan D, Merchant, Akil A, Fujishima, Naohito, Uchida, Toshiki, Calbacho, Maria, Ejduk, Anna A, O'Brien, Susan M, Jabbour, Elias J, Zhang, Hui, Sleight, Barbara J, Vandendries, Erik R, and Marks, David I

Published
2017
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5. CEBPA copy number variations in normal karyotype acute myeloid leukemia: Possible role of breakpoint-associated microhomology and chromatin status in CEBPA mutagenesis

Author

Libura, Marta, Pawełczyk, Marta, Florek, Izabella, Matiakowska, Karolina, Jaźwiec, Bożena, Borg, Katarzyna, Solarska, Iwona, Zawada, Magdalena, Czekalska, Sylwia, Libura, Jolanta, Salamanczuk, Zoriana, Jakóbczyk, Małgorzata, Mucha, Barbara, Duszeńko, Ewa, Soszyńska, Krystyna, Karabin, Karolina, Piątkowska-Jakubas, Beata, Całbecka, Małgorzata, Gajkowska-Kulig, Justyna, Gadomska, Grażyna, Kiełbiński, Marek, Ejduk, Anna, Kata, Dariusz, Grosicki, Sebastian, Kyrcz-Krzemień, Sławomira, Warzocha, Krzysztof, Kuliczkowski, Kazimierz, Skotnicki, Aleksander, Jęrzejczak, Wiesław Wiktor, and Haus, Olga

Published
2015
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8. Coexistence of hemoglobin Handsworth and alpha 3.7 kb deletion in Caucasian woman in Poland

Author

Joanna Skulimowska, Małgorzata Uhrynowska, Edyta Klimczak-Jajor, Anna Ejduk, Katarzyna Guz, and Ewa Brojer

Subjects
Mutation, Hemoglobin electrophoresis, Point mutation, Hematology, 030204 cardiovascular system & hematology, medicine.disease_cause, Compound heterozygosity, Molecular biology, 03 medical and health sciences, 0302 clinical medicine, Oncology, Genotype, medicine, Multiplex ligation-dependent probe amplification, Hemoglobin, Alpha globulin, 030215 immunology
Abstract

BackgroundThis report presents a case of an adult Polish women of Caucasian origin who was heterozygous for the nondeletional mutation: Hb Handsworth (HBA2 or HBA1: c.55G > C, p.Gly19Arg) and deletional (-α3.7) α-thalassemia mutation.MethodsThe HbA2 and HbF levels were measured by microcolumn chromatography and alkaline denaturation procedure, respectively, while electrophoresis was used to detect pathological hemoglobin fraction. The β- and α-globin genotypes were determined by DNA sequencing, gap-polymerase chain reaction, α gene triplication and MLPA.ResultsThe HbA2 and HbF levels were normal, but hemoglobin electrophoresis on agarose gel alkaline pH showed a strong band migration in a position of hemoglobin S and faint bands in the neighborhood of band A on acid electrophoresis. Molecular analysis of the alpha globin cluster detected a point mutation at codon 19 in HBA2 (c.55G > C, p.Gl- y19Arg) and deletion -α3.7.ConclusionsOur compound heterozygosity does not produce severe clinical or hematological symptoms but it is important to say that in our part of Europe such cases do appear. Molecular analysis of the alpha globin cluster is required for correct diagnosis in patients with normal HbA2 levels. Compound heterozygosity was unmasked by molecular diagnosis only.

Published
2019
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9. IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen

Author

Magdalena Zawada, Jerzy Holowiecki, Magdalena Wojtas, Sebastian Giebel, Agnieszka Przybylowicz, Anna Ejduk, I. Florek, Agnieszka Wierzbowska, Dariusz Kata, Kazimierz Kuliczkowski, Tomasz Wróbel, Beata Piatkowska-Jakubas, Przemysław Juszczynski, Marta Libura, Katarzyna Piwocka, Sylwia Czekalska, Marzena Wojtaszewska, Emilia Bialopiotrowicz, Karolina Matiakowska, Iwona Solarska, Tomasz Sacha, Patryk Gorniak, Tadeusz Robak, Elżbieta Urbanowska, Gail J. Roboz, Wiesław Wiktor Jędrzejczak, Agnieszka Sroka-Porada, Agnieszka Pluta, Wanda Knopinska, Justyna Gajkowska-Kulik, Krzysztof Warzocha, Anna Wróbel, Monika Paluszewska, Sebastian Grosicki, Karolina Karabin, Marta Pawelczyk, Bozena Jazwiec, Katarzyna Borg, Justyna Rybka, Grzegorz W. Basak, Olga Haus, Lidia Gil, Lukasz Bolkun, Agata Kominek, Grazyna Semenczuk, Agnieszka Piekarska, Krzysztof Lewandowski, Zoriana Salamanczuk, Karolina Pyziak, Katarzyna Wasilewska, Karolina Piechna, and Monika Noyszewska-Kania

Subjects
Adult, 0301 basic medicine, Oncology, medicine.medical_specialty, IDH1, Adolescent, Pharmacogenomic Variants, Daunorubicin, medicine.medical_treatment, Science, Population, Antineoplastic Agents, IDH2, Article, Acute myeloid leukaemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cancer epigenetics, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Chemotherapy, Cladribine, education, Aged, Randomized Controlled Trials as Topic, Retrospective Studies, education.field_of_study, Multidisciplinary, business.industry, Cytarabine, Middle Aged, Isocitrate Dehydrogenase, Leukemia, Myeloid, Acute, Regimen, 030104 developmental biology, 030220 oncology & carcinogenesis, Medicine, Poland, business, medicine.drug
Abstract

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) genes occur in about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation and epigenetic deregulation. We assessed the prognostic significance of IDH1/2 mutations (IDH1/2+) in 398 AML patients with normal karyotype (NK-AML), treated with daunorubicine + cytarabine (DA), DA + cladribine (DAC), or DA + fludarabine. IDH2 mutation was an independent favorable prognostic factor for 4-year overall survival (OS) in total NK-AML population (p = 0.03, censoring at allotransplant). We next evaluated the effect of addition of cladribine to induction regimen on the patients’ outcome according to IDH1/2 mutation status. In DAC group, 4-year OS was increased in IDH2+ patients, compared to IDH-wild type group (54% vs 33%; p = 0.0087, censoring at allotransplant), while no difference was observed for DA-treated subjects. In multivariate analysis, DAC independently improved the survival of IDH2+ patients (HR = 0.6 [0.37–0.93]; p = 0.024; censored at transplant), indicating that this group specifically benefits from cladribine-containing therapy. In AML cells with R140Q or R172K IDH2 mutations, cladribine restrained mutations-related DNA hypermethylation. Altogether, DAC regimen produces better outcomes in IDH2+ NK-AML patients than DA, and this likely results from the hypomethylating activity of cladribine. Our observations warrant further investigations of induction protocols combining cladribine with IDH1/2 inhibitors in IDH2-mutant.

Published
2021

10. Plerixafor for patients who fail cytokine-or chemotherapy-based stem cell mobilization: Results of a prospective study by the Polish Lymphoma Research Group (PLRG)

Author

Sylwia Oborska, Sebastian Giebel, Tomasz Ogórka, Michal Osowiecki, Paweł Steckiewicz, Magdalena Maruszak, Łukasz Targoński, Michał Taszner, Joanna Romejko-Jarosinska, Anna Czyż, Joanna Drozd-Sokołowska, Joanna Sawczuk-Chabin, Jarosław Dybko, Joanna Mańko, Wojciech Legiec, Ewa Paszkiewicz-Kozik, Maria Saduś-Wojciechowska, Anna Ejduk, and Agata Szymańska

Subjects
Oncology, medicine.medical_specialty, Chemotherapy, Mobilization, business.industry, Plerixafor, medicine.medical_treatment, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Transplantation, 03 medical and health sciences, Haematopoiesis, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Stem cell, business, Multiple myeloma, 030215 immunology, medicine.drug
Abstract

Autologous hematopoietic stem cell transplantation (autoHSCT) requires collection of sufficient number of hematopoietic stem cells. The goal of this study was to evaluate efficacy of plerixafor used in patients with lymphoid malignancies failing conventional stem cell mobilization.This was a prospective, non-interventional study. All consecutive patients (n = 109) treated with plerixafor in 11 centers were reported. The drug was used either in case of previous mobilization failure (n = 67) or interventionally, in case of insufficient CD34+ cell output during current mobilization (n = 42). Successful mobilization was defined as resulting in collection of ≥ 2 × 106 CD34+ cells/kg for single autoHSCT or ≥ 4 × 106 CD34+ cells/kg for double procedure.The overall rate of successful mobilization was 55% (55% for single and 56% for double autoHSCT). The median total number of collected CD34+ cells/kg was 2.4 (range, 0-11.5) for patients intended for a single transplantation while 4.0 (0.6-16.9) for double procedure. The number of circulating CD34+ cells increased after the use of plerixafor regardless of baseline values. The median fold increase was 3.3 (0.3-155). Data from this observational study confirm high efficacy of plerixafor used in routine clinical practice as salvage for patients with lymphoid malignancies failing conventional stem cell mobilization.

Published
2018
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11. Skuteczne leczenie ratunkowe inhibitorami kinaz tyrozynowych chorego na B-komórkową ostrą białaczkę limfoblastyczną Filadelfia-dodatnią

Author

Ilona Seferyńska, Anna Ejduk, Iwona Solarska, and Krzysztof Warzocha

Subjects
Polycythaemia, Concentration ability, medicine.medical_specialty, urogenital system, business.industry, Urology, Renal function, Hematology, Urine, medicine.disease, Fluid intake, Oncology, hemic and lymphatic diseases, medicine, Creatinine metabolism, business
Abstract

In 23 patients with polycythaemia vera and symptomatic erythrocytosis, glomerular filtration rate and urine concentration ability see article were determined under conditions of antidiuresis. The restriction of fluid intake caused a significant reduction of GFR and modified the osmotic function of the kidneys. The results were similar in both types of polycythaemia.

Published
2018
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12. IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen

Author

Libura, Marta, primary, Bialopiotrowicz, Emilia, additional, Giebel, Sebastian, additional, Wierzbowska, Agnieszka, additional, Roboz, Gail J., additional, Piatkowska-Jakubas, Beata, additional, Pawelczyk, Marta, additional, Gorniak, Patryk, additional, Borg, Katarzyna, additional, Wojtas, Magdalena, additional, Florek, Izabella, additional, Matiakowska, Karolina, additional, Jazwiec, Bozena, additional, Solarska, Iwona, additional, Noyszewska-Kania, Monika, additional, Piechna, Karolina, additional, Zawada, Magdalena, additional, Czekalska, Sylwia, additional, Salamanczuk, Zoriana, additional, Karabin, Karolina, additional, Wasilewska, Katarzyna, additional, Paluszewska, Monika, additional, Urbanowska, Elzbieta, additional, Gajkowska-Kulik, Justyna, additional, Semenczuk, Grazyna, additional, Rybka, Justyna, additional, Wrobel, Tomasz, additional, Ejduk, Anna, additional, Kata, Dariusz, additional, Grosicki, Sebastian, additional, Robak, Tadeusz, additional, Pluta, Agnieszka, additional, Kominek, Agata, additional, Piwocka, Katarzyna, additional, Pyziak, Karolina, additional, Sroka-Porada, Agnieszka, additional, Wrobel, Anna, additional, Przybylowicz, Agnieszka, additional, Wojtaszewska, Marzena, additional, Lewandowski, Krzysztof, additional, Gil, Lidia, additional, Piekarska, Agnieszka, additional, Knopinska, Wanda, additional, Bolkun, Lukasz, additional, Warzocha, Krzysztof, additional, Kuliczkowski, Kazimierz, additional, Sacha, Tomasz, additional, Basak, Grzegorz, additional, Jedrzejczak, Wieslaw Wiktor, additional, Holowiecki, Jerzy, additional, Juszczynski, Przemysław, additional, and Haus, Olga, additional

Published
2021
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13. Blinatumomab — nowy lek u chorych na nawrotową/ /oporną ostrą białaczkę limfoblastyczną

Author

Ewa Lech-Marańda, Anna Ejduk, and Joanna Sawczuk-Chabin

Subjects
Oncology, medicine.medical_specialty, Chemotherapy, business.industry, medicine.drug_class, medicine.medical_treatment, Standard treatment, Hematology, Hematopoietic stem cell transplantation, Immunotherapy, Monoclonal antibody, Targeted therapy, Refractory, Internal medicine, Immunology, medicine, Blinatumomab, business, medicine.drug
Abstract

The long term prognosis of adult patients with relapsed/refractory (R/R) acute lymphoblastic leu­kemia (ALL) is poor. There is no standard treatment for relapsed ALL and reinduction therapy should only be a “bridge treatment” in allogeneic hematopoietic stem cell transplantation (allo- -HSCT). In spite of obtaining an initial response to treatment, the duration of response using standard chemotherapy is usually short and the next relapses are chemoresistant. Immunotherapy with monoclonal antibodies as a targeted therapy represents a novel approach for treating patients with R/R ALL. The objective of immunotherapy is to improve the relapse-free and overall survival without increasing the toxicity of treatment. In this review, the mechanism of action and clini­cal efficacy of the novel bispecific antibody blinatumomab is discussed. The European Medicines Agency approved blinatumomab in 2015 for treating adult patients with Philadelphia chromosome negative R/R B-ALL.

Published
2017
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14. Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype – retrospective analysis of Polish Adult Leukemia Group (PALG)

Author

Monika Siemieniuk-Rys, Ewa Duszenko, Ewa Wawrzyniak, Marzena Watek, Aleksandra Kotkowska, Katarzyna Skonieczka, Wanda Knopinska-Posluszny, Sebastian Grosicki, Aleksandra Gołos, Jadwiga Hołojda, Justyna Rybka, Jerzy Holowiecki, Agnieszka Pluta, Barbara Pienkowska-Grela, Malgorzata Wach, Lidia Gil, Agnieszka Wierzbowska, Tadeusz Robak, Mariola Iliszko, Anna Jaskowiec, Renata Woroniecka, Anna Jachalska, Malgorzata Jarmuz-Szymczak, Olga Haus, Maria Czyżewska, Anna Ejduk, Barbara Mucha, Marta Szarawarska, Anna Przybylowicz-Chalecka, Agnieszka Kopacz, and Agnieszka Klonowska

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Monosomy, Pathology, medicine.medical_treatment, Karyotype, Hematopoietic stem cell transplantation, Biology, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Complex Karyotype, medicine, Humans, Transplantation, Homologous, Cladribine, Survival analysis, Aged, Retrospective Studies, Aged, 80 and over, Chromosome Aberrations, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, Survival Analysis, Leukemia, Myeloid, Acute, Regimen, Leukemia, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Poland, Biomarkers, 030215 immunology, medicine.drug
Abstract

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK− and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK− but not in MK+ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+.

Published
2016
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15. Real life outcomes of patients aged >= 75 years old with acute promyelocytic leukemia: experience of the PETHEMA registry

Author

Salamero O, Mart?nez-Cuadr?n D, Sobas M, Benavente C, Vives S, De la Serna J, P?rez-Encinas M, Escoda L, Gil C, Brunet S, Ramos F, Esteve J, Amigo M, Krsnik I, Manso F, Arias J, Gonz?lez-Campos J, Serrano J, Oleksiuk J, Barrios M, Garc?a-Boyero R, Novo A, Sanz M, Montesinos P, Helbig G, Holowiecka A, Armatys A, Hawrylecka D, Golos A, Ejduk A, Majcherek M, Skret A, Czyzewska J, Grosicki S, Zarzycka E, Watek M, Piatkowska-Jakubas B, Holojda J, Pluta A, Podhorecka M, Gromek T, Guzicka E, Charlinski G, Paluszewska M, de Heredia J, Hern?ndez J, Rom?n A, de la Serna J, Negri S, Ray?n C, Fern?ndez-Calvo F, D?az-Mediavilla J, Tormo M, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Rivas C, Esquembre C, Garc?a R, Alcal? A, L?pez J, Rubio V, Linares M, Ribera J, San Miguel J, Deb?n G, de la C?mara R, Molines A, Loureiro C, Allegue M, Amador L, Mart? J, Madero L, Lassaletta A, Cabezudo M, Garc?a-Larana J, Rojas R, Ortega F, Pe?arrubia M, Puente F, Lopez-Ibor B, Bergua J, Ib??ez J, S?nchez P, Font L, Guinea J, Montero A, Gonz?lez M, Mart?n G, Mart?nez J, Verdeguer A, Garc?a P, Conde E, Garc?a J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonz?lez J, P?rez I, Molina J, Mateos M, Ardaiz M, Rodr?guez-Calvillo M, Poder?s C, Arn?n M, Duarte R, D?az-Morfa M, Mart?n-Chac?n E, Calvo-Villas J, Garc?a-Belmonte D, Hern?ndez-Maraver D, Miskiewicz W, PETHEMA Grp, and PALG Grp

Subjects
induction mortality in APL, APL real life outcomes, Elderly APL, APL prognostic factors, neoplasms
Abstract

Acute promyelocytic leukemia is infrequent among patients aged >= 75 years old, a population that is rarely eligible for clinical protocols. This study aims to analyze the treatment strategies and clinical outcomes of very old APL patients reported to the international PETHEMA registry. Between 1997 and 2017, among 2501 APL cases registered 120 were >= 75 years old. Treatment approaches were: AIDA regimen, 79 patients; ATRA alone, 23; 16, supportive care (SC) and 2, other strategies. Patients treated with AIDA were younger, had better ECOG and lower leukocytes. Complete remission (CR) was achieved in 65% of AIDA-group vs. 45% in the ATRA-group, being infections followed by bleeding the most frequent causes of induction death. Patients in CR after AIDA showed 3-year DFS of 73%. Our real-life series of very old APL patients provides a reference basis for future treatment strategies aiming to improve clinical outcomes in this challenging population.

Published
2019

16. An analysis of the impact of CD56 expression in de novo acute promyelocytic leukemia patients treated with upfront all-trans retinoic acid and anthracycline-based regimens

Author

Sobas M, Montesinos P, Boluda B, Bernal T, Vellenga E, Nomdedeu J, Gonzalez-Campos J, Chillon M, Holowiecka A, Esteve J, Bergua J, Gonzalez-Sanmiguel J, Gil-Cortes C, Tormo M, Salamero O, Manso F, Fernandez I, de la Serna J, Moreno M, Perez-Encinas M, Krsnik I, Ribera J, Escoda L, Lowenberg B, Sanz M, de Heredia J, Hernandez J, Arias J, Ramos F, Roman A, Negri S, Rayon C, Fernandez-Calvo F, Diaz-Mediavilla J, Gil C, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Esquembre C, Garcia R, Alcala A, Lopez J, Rubio V, Amigo M, Linares M, San Miguel J, Coruna A, Deben G, de la Camara R, Molines A, Loureiro C, Allegue M, Amador L, Marti J, Madero L, Lassaletta A, Cabezudo M, Garcia-Larana J, Rojas R, Ortega F, Penarrubia M, Puente F, Lopez-Ibor B, Brunet S, Ibanez J, Sanchez P, Novo A, Guinea J, Montero A, Gonzalez M, Martin G, Martinez J, Verdeguer A, Garcia P, Conde E, Garcia J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonzalez J, Perez I, Molina J, Mateos M, Ardaiz M, Rodriguez-calvillo M, Poderos C, Arnan M, Duarte R, Diaz-Morfa M, Martin-Chacon E, Calvo-Villas J, Garcia-Belmonte D, Hernandez-Maraver D, Ossenkoppele G, van der Lelie J, Sonneveld P, Zijlmans M, Maertens J, de Valk B, Wijermans P, de Groot M, Schouten H, Biesma D, van Marwijk M, de Lisa E, Golos A, Ejduk A, Armatys A, Zarzycka E, Knopinska W, Miskiewicz W, Jastrzab B, Pluta A, Paluszewska M, Podhorecka M, Gromek T, Jakubas B, Majcherek M, Skret A, Watek M, Charlinski G, Calbecka M, Becht R, Gadomska A, Rzenno E, Piszcz J, Grosicki S, Palmer L, Ciarlo S, Bezares F, Rojas F, Longoni H, Gelemur M, Fazio P, Canepa C, Saba S, Balladares G, Negri P, Giunta M, Milone J, Lafalse D, Sossa C, Jaramillo F, Mayer J, Protivankova M, Scwarz J, PETHEMA Cooperative Grp, HOVON Cooperative Grp, PALG Cooperative Grp, and GATLA Cooperative Grp

Subjects
relapse, Acute promyelocytic leukemia, CD56, ATRA, chemotherapy, prognostic
Abstract

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p < .001; intermediate 23% versus 7%, p < .001; and high-risk 42% versus 21%, p = .007). In the multivariate analysis, CD56 + (p < .0001), higher relapse-risk score (p = .001), and male gender (p = .05) retained the independent predictive value. CD56+ APL also showed a greater risk of CNS relapse (6% versus 1%, p < .001) and lower 5-year OS (75% versus 83%, p = .003). The AIDA-based LPA2012 trial, with an intensified consolidation schedule for CD56+ APL, will elucidate whether an intensified consolidation schedule could mitigate the relapse rate in this setting.

Published
2019

17. Clinical significance of complex karyotype at diagnosis in pediatric and adult patients with de novo acute promyelocytic leukemia treated with ATRA and chemotherapy

Author

Labrador J, Luno E, Vellenga E, Brunet S, Gonzalez-Campose J, Chillon M, Holowiecka A, Esteve J, Bergua J, Gonzalez-Sanmiguel J, Gil C, Tormo M, Salamero O, Manso F, Fernandez I, de laSerna J, Moreno M, Perez-Encinas M, Krsnik I, Ribera J, Cervera J, Calasanz M, Boluda B, Sobas M, Lowenberg B, Sanz M, Montesinos P, Palmer L, Ciarlo S, Bezares F, Rojas F, Longoni H, Gelemur M, Fazio P, Canepa C, Saba S, Balladares G, Negri P, Giunta M, Milone J, Prates M, Lafalse D, Sossa C, Jaramillo F, Mayer J, Protivankova M, Scwarz J, Holowiecka-Goral A, Jakubas B, Skret-Norwicz A, Bizgalska-Skrzypek P, Pluta A, Becht R, Kielbinski M, Watek M, Paluszewska M, Gadomska A, Rzenno E, Piszcz J, Ejduk A, Dobrzanska J, Calbecka M, Kostyra A, Malek M, Grosicki S, Knopinska W, Beltran de Heredia J, Hernandez J, Arias J, Ramos F, Roman A, de la Serna J, Negri S, Rayon C, Fernandez-Calvo F, Diaz-Mediavilla J, Olave M, Amutio E, Pedro C, Gorosquieta A, Viguria M, Zudaire M, Molero T, Sayas M, Guardia R, Rivas C, Esquembre C, Garcia R, Alcala A, Lopez J, Rubio V, Amigo M, Linares M, Gonzalez San Miguel J, Deben G, Escoda L, de la Camara R, Molines A, Loureiro C, Allegue M, Amador L, Marti J, Madero L, Lassaletta A, Cabezudo M, Garcia-Larana J, Rojas R, Ortega F, Penarrubia M, Puente F, Lopez-Ibor B, Ibanez J, Sanchez P, Novo A, Font L, Guinea J, Montero A, Gonzalez M, Martin G, Martinez J, Verdeguer A, Garcia P, Conde E, Garcia J, Capote F, Bueno J, Bastida P, Rubio A, Fuster J, Gonzalez J, Perez I, Molina J, Mateos M, Ardaiz M, Rodriguez-calvillo M, Poderos C, Arnan M, Duarte R, Diaz-Morfa M, Martin-Chacon E, Calvo-Villas J, Garcia-Belmonte D, Hernandez-Maraver D, Ossenkoppele G, van der Lelie J, Sonneveld P, Zijlmans M, Maertens J, de Valk B, Wijermans P, de Groot M, Schouten H, Biesma D, Kooy M, de Lisa E, PETHEMA Grp, HOVON Grp, PALG Grp, and GATLA Grp

Subjects
relapse, complex karyotype, Acute promyelocytic leukemia, ATRA, chemotherapy, prognostic
Abstract

Although additional cytogenetic abnormalities (ACA) do not affect the prognosis of patients with t(15;17) acute promyelocytic leukemia (APL), the role of a complex karyotype (CK) is yet to be clarified. We aimed to investigate the relationship of CK with relapse incidence in 1559 consecutive APL patients enrolled in three consecutive trials. Treatment consisted of AIDA induction followed by risk-adapted consolidation. A CK (CK) was defined as the presence of >= 2 ACA, and a very CK (CK+) as >= 3 ACA. Eighty-nine patients (8%) had a CK, of whom 41 (4%) had CK+. The 5-year cumulative incidence of relapse (CIR) in patients with CK was 18%, and 12% in those with

Published
2019

19. A novel IGH@ gene rearrangement associated with CDKN2A/B deletion in young adult B-cell acute lymphoblastic leukemia

Author

Martina Rincic, Isabel M. Carreira, Jolanta Rygier, Britta Meyer, Thomas Liehr, Beata Grygalewicz, Anna Ejduk, Joana B. Melo, Moneeb A.K. Othman, and Barbara Pienkowska-Grela

Subjects
0301 basic medicine, Cancer Research, Acute leukemia, medicine.medical_specialty, medicine.diagnostic_test, Cytogenetics, Cancer, Karyotype, Biology, medicine.disease, Molecular biology, Molecular cytogenetics, 03 medical and health sciences, Leukemia, 030104 developmental biology, 0302 clinical medicine, immunoglobulin heavy locus gene rearrangement, cyclin-dependent kinase inhibitor 2A, B deletion, B-cell acute lymphoblastic leukemia, array-comparative genomic hybridization, molecular cytogenetics, Oncology, 030220 oncology & carcinogenesis, medicine, Comparative genomic hybridization, Fluorescence in situ hybridization
Abstract

Acquired copy number changes are common in acute leukemia. They are reported as recurrent amplifications or deletions (del), and may be indicative of involvement of oncogenes or tumor suppressor genes in acquired disease, as well as serving as potential biomarkers for prognosis or as targets for molecular therapy. The present study reported a gain of copy number of 14q13 to 14q32, leading to immunoglobulin heavy chain locus splitting in a young adult female. To the best of our knowledge, this rearrangement has not been previously reported in B-cell acute lymphoblastic leukemia (ALL). Low resolution banding cytogenetics performed at the time of diagnosis revealed a normal karyotype. However, retrospective application of fluorescence in situ hybridization (FISH) banding and locus-specific FISH probes, as well as multiplex ligation-dependent probe amplification and high resolution array-comparative genomic hybridization, revealed previously hidden aberrations. Overall, a karyotype of 46, XX, del(9) (p21.3 p21.3), derivative(14) (pter-> q32.33:: q32.33-> q13 ::q32.33-> qter) was determined. The patient was treated according to the Polish Adult Leukemia Group protocol and achieved complete remission. The results of the present study indicate that a favorable prognosis is associated with these aberrations when the aforementioned treatment is administered.

Published
2016
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20. Plerixafor for patients who fail cytokine-or chemotherapy-based stem cell mobilization: Results of a prospective study by the Polish Lymphoma Research Group (PLRG)

Author

Giebel, Sebastian, primary, Oborska, Sylwia, additional, Romejko-Jarosinska, Joanna, additional, Dybko, Jarosław, additional, Mańko, Joanna, additional, Sawczuk-Chabin, Joanna, additional, Szymańska, Agata, additional, Legieć, Wojciech, additional, Czyż, Anna, additional, Maruszak, Magdalena, additional, Saduś-Wojciechowska, Maria, additional, Drozd-Sokołowska, Joanna, additional, Steckiewicz, Paweł, additional, Ejduk, Anna, additional, Paszkiewicz-Kozik, Ewa, additional, Ogórka, Tomasz, additional, Osowiecki, Michał, additional, Targoński, Łukasz, additional, and Taszner, Michał, additional

Published
2018
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22. Cladribine added to daunorubicin-cytarabine induction prolongs survival of FLT3-ITD+ normal karyotype AML patients

Author

Libura, Marta, Giebel, Sebastian, Piatkowska-Jakubas, Beata, Pawelczyk, Marta, Florek, Izabella, Matiakowska, Karolina, Jazwiec, Bozena, Borg, Katarzyna, Solarska, Iwona, Zawada, Magdalena, Czekalska, Sylwia, Libura, Jolanta, Jakobczyk, Malgorzata, Karabin, Karolina, Paluszewska, Monika, Calbecka, Malgorzata, Gajkowska-Kulik, Justyna, Gadomska, Grazyna, Kielbinski, Marek, Ejduk, Anna, Kata, Dariusz, Grosicki, Sebastian, Wierzbowska, Agnieszka, Kyrcz-Krzemien, Slawomira, Warzocha, Krzysztof, Kuliczkowski, Kazimierz, Skotnicki, Aleksander, Holowiecki, Jerzy, Jedrzejczak, Wieslaw Wiktor, and Haus, Olga

Published
2016
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23. Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer's disease and elderly controls after oral administration of sembragiline

Author

Anton Forsberg, Niels Andreasen, Ryuji Nakao, Stephane Nave, Per Stenkrona, Patrik Fazio, Benedicte Ricci, Candice Jamois, Christer Halldin, Zbigniew Ejduk, Andrea Varrone, Ulrika Akenine, N. Seneca, Stefan Sturm, Robert A. Comley, and Nabil Al-Tawil

Subjects
0301 basic medicine, Male, Positron emission tomography, Monoamine Oxidase Inhibitors, medicine.drug_class, Central nervous system, Population, Administration, Oral, Sembragiline, Pharmacology, Neuroprotection, MAO-B, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Monoaminergic, Acetamides, medicine, Humans, Radiology, Nuclear Medicine and imaging, education, Monoamine Oxidase, Neuroinflammation, Aged, Monoamine oxidase inhibitor, education.field_of_study, business.industry, General Medicine, Middle Aged, Pyrrolidinones, 3. Good health, 030104 developmental biology, Monoamine neurotransmitter, medicine.anatomical_structure, Radiology Nuclear Medicine and imaging, Anesthesia, Case-Control Studies, Positron-Emission Tomography, Female, Original Article, Monoamine oxidase B, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Protein Binding
Abstract

Purpose In Alzheimer’s disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577 and EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD. Methods This study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control (EC) subjects. Positron emission tomography (PET) scans using [11C]-L-deprenyl-D2 radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6–15 days. Results At steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an Emax of ∼80–90 % across brain regions of interest and in an EC50 of 1–2 ng/mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition. Conclusions This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD. Electronic supplementary material The online version of this article (doi:10.1007/s00259-016-3510-6) contains supplementary material, which is available to authorized users.

Published
2016

24. Cladribine added to daunorubicin-cytarabine induction prolongs survival of FLT3-ITD+ normal karyotype AML patients

Author

Sylwia Czekalska, Monika Paluszewska, Sebastian Grosicki, Sebastian Giebel, Iwona Solarska, Slawomira Kyrcz-Krzemien, Aleksander B. Skotnicki, Malgorzata Jakobczyk, Karolina Karabin, Katarzyna Borg, Karolina Matiakowska, Marek Kielbinski, Anna Ejduk, Wiesław Wiktor Jędrzejczak, Malgorzata Calbecka, Krzysztof Warzocha, Jerzy Holowiecki, I. Florek, Justyna Gajkowska-Kulik, Marta Pawelczyk, Bozena Jazwiec, Jolanta Libura, Beata Piatkowska-Jakubas, Magdalena Zawada, Olga Haus, Kazimierz Kuliczkowski, Grażyna Gadomska, Agnieszka Wierzbowska, Marta Libura, and Dariusz Kata

Subjects
Oncology, medicine.medical_specialty, Myeloid, Daunorubicin, Karyotype, Immunology, Pharmacology, Biochemistry, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, Gene Duplication, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Gene duplication, medicine, Humans, Cladribine, business.industry, Cytarabine, hemic and immune systems, Cell Biology, Hematology, medicine.disease, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, medicine.anatomical_structure, fms-Like Tyrosine Kinase 3, 030220 oncology & carcinogenesis, embryonic structures, Fms-Like Tyrosine Kinase 3, business, psychological phenomena and processes, 030215 immunology, medicine.drug
Abstract

To the editor: Internal tandem duplication in the FLT3 gene ( FLT3- ITD) has been recognized as a marker conferring poor outcome in patients with normal karyotype acute myeloid leukemia (NK-AML).[1][1] Because of the inferior outcome of FLT3- ITD+ NK-AML patients when treated with standard

Published
2016

26. Comparison of high-resolution melting analysis with direct sequencing for the detection of recurrent mutations in DNA methyltransferase 3A and isocitrate dehydrogenase 1 and 2 genes in acute myeloid leukemia patients

Author

Monika Prochorec-Sobieszek, Patryk Górniak, Krzysztof Warzocha, Katarzyna Borg, Hanna Makuch-Lasica, Anna Ejduk, Ewa Lech-Marańda, Grazyna Nowak, and Przemyslaw Juszczynski

Subjects
0301 basic medicine, Adult, Male, DNA Mutational Analysis, Gene Expression, Biology, Nucleic Acid Denaturation, DNA sequencing, High Resolution Melt, DNA Methyltransferase 3A, Epigenesis, Genetic, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0302 clinical medicine, Humans, Epigenetics, DNA (Cytosine-5-)-Methyltransferases, Gene, Retrospective Studies, COLD-PCR, Genetics, Sanger sequencing, Myeloid leukemia, High-Throughput Nucleotide Sequencing, Hematology, General Medicine, Molecular biology, Isocitrate Dehydrogenase, Leukemia, Myeloid, Acute, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Mutation, symbols, Female, DNA
Abstract

Acute myeloid leukemia (AML) cells harbor frequent mutations in genes responsible for epigenetic modifications. Increasing evidence of clinical role of DNMT3A and IDH1/2 mutations highlights the need for a robust and inexpensive test to identify these mutations in routine diagnostic work-up. Herein, we compared routinely used direct sequencing method with high-resolution melting (HRM) assay for screening DNMT3A and IDH1/2 mutations in patients with AML. We show very high concordance between HRM and Sanger sequencing (100% samples for IDH2-R140 and DNMT3-R882 mutations, 99% samples for IDH1-R132 and IDH2-R172 mutations). HRM method reported no false-negative results, suggesting that it can be used for mutations screening. Moreover, HRM displayed much higher sensitivity in comparison with DNA sequencing in all assessed loci. With Sanger sequencing, robust calls were observed when the sample contained 50% of mutant DNA in the background of wild-type DNA. In marked contrast, the detection limit of HRM improved down to 10% of mutated DNA. Given the ubiquitous presence of wild-type DNA background in bone marrow aspirates and clonal variations regarding mutant allele burden, these results favor HRM as a sensitive, specific, labor-, and cost-effective tool for screening and detection of mutations in IDH1/2 and DNMT3A genes in patients with AML.

Published
2015

27. Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer’s disease and elderly controls after oral administration of sembragiline

Author

Sturm, Stefan, primary, Forsberg, Anton, additional, Nave, Stephane, additional, Stenkrona, Per, additional, Seneca, Nicholas, additional, Varrone, Andrea, additional, Comley, Robert A., additional, Fazio, Patrik, additional, Jamois, Candice, additional, Nakao, Ryuji, additional, Ejduk, Zbigniew, additional, Al-Tawil, Nabil, additional, Akenine, Ulrika, additional, Halldin, Christer, additional, Andreasen, Niels, additional, and Ricci, Benedicte, additional

Published
2016
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28. Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype – retrospective analysis of Polish Adult Leukemia Group (PALG)

Author

Wierzbowska, Agnieszka, primary, Wawrzyniak, Ewa, additional, Siemieniuk-Rys, Monika, additional, Kotkowska, Aleksandra, additional, Pluta, Agnieszka, additional, Golos, Aleksandra, additional, Robak, Tadeusz, additional, Szarawarska, Marta, additional, Jaskowiec, Anna, additional, Duszenko, Ewa, additional, Rybka, Justyna, additional, Holojda, Jadwiga, additional, Grosicki, Sebastian, additional, Pienkowska-Grela, Barbara, additional, Woroniecka, Renata, additional, Ejduk, Anna, additional, Watek, Marzena, additional, Wach, Malgorzata, additional, Mucha, Barbara, additional, Skonieczka, Katarzyna, additional, Czyzewska, Maria, additional, Jachalska, Anna, additional, Klonowska, Agnieszka, additional, Iliszko, Mariola, additional, Knopinska-Posluszny, Wanda, additional, Jarmuz-Szymczak, Malgorzata, additional, Przybylowicz-Chalecka, Anna, additional, Gil, Lidia, additional, Kopacz, Agnieszka, additional, Holowiecki, Jerzy, additional, and Haus, Olga, additional

Published
2016
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31. Favorable outcome of patients with normal karyotype acute myeloid leukemia harboring FLT3-ITD and treated with cladribine added to daunorubicin and cytarabine induction

Author

Libura, M., primary, Giebel, S., additional, Piątkowska-Jakubas, B., additional, Pawełczyk, M. Przestrzelska, additional, Florek, I., additional, Matiakowska, K., additional, Jaźwiec, B., additional, Borg, K., additional, Solarska, I., additional, Zawada, M., additional, Czekalska, S., additional, Libura, J., additional, Jakóbczyk, M., additional, Karabin, K., additional, Całbecka, M., additional, Gajkowska-Kulig, J., additional, Gadomska, G., additional, Kiełbiński, M., additional, Ejduk, A., additional, Kata, D., additional, Grosicki, S., additional, Wierzbowska, A., additional, Kyrcz-Krzemień, S., additional, Warzocha, K., additional, Kuliczkowski, K., additional, Skotnicki, A., additional, Hołowiecki, J., additional, Jedrzejczak, W.W., additional, and Haus, O., additional

Published
2015
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34. Comparison of high-resolution melting analysis with direct sequencing for the detection of recurrent mutations in DNA methyltransferase 3A and isocitrate dehydrogenase 1 and 2 genes in acute myeloid leukemia patients

Author

Gorniak, Patryk, primary, Ejduk, Anna, additional, Borg, Katarzyna, additional, Makuch-Lasica, Hanna, additional, Nowak, Grazyna, additional, Lech-Maranda, Ewa, additional, Prochorec-Sobieszek, Monika, additional, Warzocha, Krzysztof, additional, and Juszczynski, Przemyslaw, additional

Published
2015
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36. Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype – retrospective analysis of Polish Adult Leukemia Group (PALG).

Author

Wierzbowska, Agnieszka, Wawrzyniak, Ewa, Siemieniuk-Rys, Monika, Kotkowska, Aleksandra, Pluta, Agnieszka, Golos, Aleksandra, Robak, Tadeusz, Szarawarska, Marta, Jaskowiec, Anna, Duszenko, Ewa, Rybka, Justyna, Holojda, Jadwiga, Grosicki, Sebastian, Pienkowska-Grela, Barbara, Woroniecka, Renata, Ejduk, Anna, Watek, Marzena, Wach, Malgorzata, Mucha, Barbara, and Skonieczka, Katarzyna

Subjects
KARYOTYPES, CHROMOSOMAL proteins, CHROMOSOME abnormalities, CYTOGENETICS, ACUTE myeloid leukemia treatment, DIAGNOSIS, THERAPEUTICS
Abstract

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK−and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK−but not in MK+ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+. [ABSTRACT FROM AUTHOR]

Published
2017
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38. Comparison of high-resolution melting analysis with direct sequencing for the detection of recurrent mutations in DNA methyltransferase 3 A and isocitrate dehydrogenase 1 and 2 genes in acute myeloid leukemia patients.

Author

Gorniak, Patryk, Ejduk, Anna, Borg, Katarzyna, Makuch‐Lasica, Hanna, Nowak, Grazyna, Lech‐Maranda, Ewa, Prochorec‐Sobieszek, Monika, Warzocha, Krzysztof, and Juszczynski, Przemyslaw

Subjects
*ACUTE myeloid leukemia, *EPIGENESIS, *GENETIC mutation, *NUCLEOTIDE sequence, *BONE marrow
Abstract

Acute myeloid leukemia ( AML) cells harbor frequent mutations in genes responsible for epigenetic modifications. Increasing evidence of clinical role of DNMT3A and IDH1/2 mutations highlights the need for a robust and inexpensive test to identify these mutations in routine diagnostic work-up. Herein, we compared routinely used direct sequencing method with high-resolution melting ( HRM) assay for screening DNMT3A and IDH1/ 2 mutations in patients with AML. We show very high concordance between HRM and Sanger sequencing (100% samples for IDH2-R140 and DNMT3-R882 mutations, 99% samples for IDH1-R132 and IDH2-R172 mutations). HRM method reported no false-negative results, suggesting that it can be used for mutations screening. Moreover, HRM displayed much higher sensitivity in comparison with DNA sequencing in all assessed loci. With Sanger sequencing, robust calls were observed when the sample contained 50% of mutant DNA in the background of wild-type DNA. In marked contrast, the detection limit of HRM improved down to 10% of mutated DNA. Given the ubiquitous presence of wild-type DNA background in bone marrow aspirates and clonal variations regarding mutant allele burden, these results favor HRM as a sensitive, specific, labor-, and cost-effective tool for screening and detection of mutations in IDH1/2 and DNMT3A genes in patients with AML. [ABSTRACT FROM AUTHOR]

Published
2016
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39. Treatment of elderly patients with acute myeloid leukemia adjusted for performance status and presence of comorbidities: a Polish Adult Leukemia Group study.

Author

Budziszewska, Bozena Katarzyna, Pluta, Agnieszka, Sulek, Kazimierz, Wierzbowska, Agnieszka, Robak, Tadeusz, Giebel, Sebastian, Holowiecka-Goral, Aleksandra, Sawicki, Waldemar, Ejduk, Anna, Patkowska, Elzbieta, Manko, Joanna, Gajkowska-Kulik, Justyna, Piszcz, Jaroslaw, Mordak-Domagala, Monika, Madry, Krzysztof, Holowiecki, Jerzy, Kyrcz-Krzemien, Slawomira, Nowakowska-Domagala, Maria, Dmoszynska, Anna, and Calbecka, Malgorzata

Subjects
ACUTE myeloid leukemia treatment, OLDER patients, COMORBIDITY, CANCER chemotherapy, CANCER patients
Abstract

This prospective study estimated outcomes in 509 elderly patients with acute myeloid leukemia (AML) with different treatment approaches depending on Eastern Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity Index (CCI). Patients were stratified into fit (ECOG 0–2 and CCI 0–2) or frail (ECOG > 2 and/or CCI > 2) groups. Fit patients with CCI 0 received intensive chemotherapy whilst reduced-intensive chemotherapy (R-IC) was given to those with CCI 1–2. Frail patients received best supportive therapy. Fit patients presented a longer overall survival (OS) than frail subjects, but 8-week mortality rates were similar. The complete response (CR) rate between fit CCI 0 and CCI 1–2 subgroups was significantly different. Both of the fit subgroups showed similar 8-week mortality rates and OS probabilities. Allocating fit patients with CCI 1–2 to R-IC enabled an increase in the group of elderly patients who could be treated with the intention of inducing remission. [ABSTRACT FROM PUBLISHER]

Published
2015
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40. Cladribine added to daunorubicin-cytarabine induction prolongs survival of FLT3-ITD+normal karyotype AML patients

Author

Libura, Marta, Giebel, Sebastian, Piatkowska-Jakubas, Beata, Pawelczyk, Marta, Florek, Izabella, Matiakowska, Karolina, Jazwiec, Bozena, Borg, Katarzyna, Solarska, Iwona, Zawada, Magdalena, Czekalska, Sylwia, Libura, Jolanta, Jakobczyk, Malgorzata, Karabin, Karolina, Paluszewska, Monika, Calbecka, Malgorzata, Gajkowska-Kulik, Justyna, Gadomska, Grazyna, Kielbinski, Marek, Ejduk, Anna, Kata, Dariusz, Grosicki, Sebastian, Wierzbowska, Agnieszka, Kyrcz-Krzemien, Slawomira, Warzocha, Krzysztof, Kuliczkowski, Kazimierz, Skotnicki, Aleksander, Holowiecki, Jerzy, Jedrzejczak, Wieslaw Wiktor, and Haus, Olga

Published
2016
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