135 results on '"Hjorth-Hansen H"'
Search Results
2. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
- Author
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Hochhaus, A., Saussele, S., Rosti, G., Mahon, F.-X., Janssen, J.J.W.M., Hjorth-Hansen, H., Richter, J., and Buske, C.
- Published
- 2017
- Full Text
- View/download PDF
3. Safety and efficacy of the combination of pegylated interferon-α2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients
- Author
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Hjorth-Hansen, H, Stentoft, J, Richter, J, Koskenvesa, P, Höglund, M, Dreimane, A, Porkka, K, Gedde-Dahl, T, Gjertsen, B T, Gruber, F X, Stenke, L, Eriksson, K M, Markevärn, B, Lübking, A, Vestergaard, H, Udby, L, Bjerrum, O W, Persson, I, Mustjoki, S, and Olsson-Strömberg, U
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- 2016
- Full Text
- View/download PDF
4. IL1RAP expression as a measure of leukemic stem cell burden at diagnosis of chronic myeloid leukemia predicts therapy outcome
- Author
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Landberg, N, Hansen, N, Askmyr, M, Ågerstam, H, Lassen, C, Rissler, M, Hjorth-Hansen, H, Mustjoki, S, Järås, M, Richter, J, and Fioretos, T
- Published
- 2016
- Full Text
- View/download PDF
5. P950: COMBINED PROTEASOME AND AUTOPHAGY INHIBITION IN RELAPSED/REFRACTORY MULTIPLE MYELOMA – A PHASE I TRIAL OF HYDROXYCHLOROQUINE, CARFILZOMIB AND DEXAMETHASONE
- Author
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Slørdahl, T. S., primary, Askeland, F. B., additional, Hanssen, M. S. S., additional, Sundt-Hansen, S. M., additional, Vethe, N. T., additional, Hjorth-Hansen, H., additional, Fenstad, M. H., additional, Waage, A., additional, Hjertner, Ø., additional, Schjesvold, F., additional, and Sundan, A., additional
- Published
- 2022
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6. Molecular status 36 months after TKI discontinuation in CML is highly predictive for subsequent loss of MMR—final report from AFTER-SKI
- Author
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Richter, J. Lübking, A. Söderlund, S. Lotfi, K. Markevärn, B. Själander, A. Stenke, L. Deneberg, S. Ahlstrand, E. Myhr-Eriksson, K. Panayiotidis, P. Gedde-Dahl, T. Žáčková, D. Mayer, J. Olsson-Strömberg, U. Mahon, F.-X. Saussele, S. Hjorth-Hansen, H. Koskenvesa, P.
- Published
- 2021
7. Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients
- Author
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Mustjoki, S, Richter, J, Barbany, G, Ehrencrona, H, Fioretos, T, Gedde-Dahl, T, Gjertsen, B T, Hovland, R, Hernesniemi, S, Josefsen, D, Koskenvesa, P, Dybedal, I, Markevärn, B, Olofsson, T, Olsson-Strömberg, U, Rapakko, K, Thunberg, S, Stenke, L, Simonsson, B, Porkka, K, and Hjorth-Hansen, H
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- 2013
- Full Text
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8. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
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Mustjoki, S, Ekblom, M, Arstila, T P, Dybedal, I, Epling-Burnette, P K, Guilhot, F, Hjorth-Hansen, H, Höglund, M, Kovanen, P, Laurinolli, T, Liesveld, J, Paquette, R, Pinilla-Ibarz, J, Rauhala, A, Shah, N, Simonsson, B, Sinisalo, M, Steegmann, J L, Stenke, L, and Porkka, K
- Published
- 2009
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9. A novel Bcr-Abl splice isoform is associated with the L248V mutation in CML patients with acquired resistance to imatinib
- Author
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Gruber, F X, Hjorth-Hansen, H, Mikkola, I, Stenke, L, and Johansen, T
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- 2006
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10. Second-generation TKI dasatinib inhibits proliferation of mesenchymal stem cells and osteoblast differentiation in vitro
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Jönsson, S, Hjorth-Hansen, H, Olsson, B, Wadenvik, H, Sundan, A, and Standal, T
- Published
- 2010
- Full Text
- View/download PDF
11. Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia
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Hjorth-Hansen, H., Seidel, C., Lamvik, J., Börset, M., Sundan, A., and Waage, A.
- Published
- 1999
12. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial
- Author
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Saussele, S. Richter, J. Guilhot, J. Gruber, F.X. Hjorth-Hansen, H. Almeida, A. Janssen, J.J.W.M. Mayer, J. Koskenvesa, P. Panayiotidis, P. Olsson-Strömberg, U. Martinez-Lopez, J. Rousselot, P. Vestergaard, H. Ehrencrona, H. Kairisto, V. Machová Poláková, K. Müller, M.C. Mustjoki, S. Berger, M.G. Fabarius, A. Hofmann, W.-K. Hochhaus, A. Pfirrmann, M. Mahon, F.-X. Ossenkoppele, G. Pagoni, M.N. Söderlund, S. Escoffre-Barbe, M. Etienne, G. Dengler, J. Huguet, F. von Bubnoff, N. Klamova, H. Faber, E. Guilhot, F. Lotfi, K. Rea, D. Brümmendorf, T.H. de Greef, G.E. Stenke, L. Nicolini, F.E. Legros, L. Burchert, A. Voglova, J. Charbonnier, A. Gyan, E. Kunzmann, V. Westerweel, P.E. EURO-SKI investigators
- Abstract
Background: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. Methods: In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres in 11 countries. Eligible patients had chronic-phase chronic myeloid leukaemia, had received any TKI for at least 3 years (without treatment failure according to European LeukemiaNet [ELN] recommendations), and had a confirmed deep molecular response for at least 1 year. The primary endpoint was molecular relapse-free survival, defined by loss of major molecular response (MMR; >0·1% BCR-ABL1 on the International Scale) and assessed in all patients with at least one molecular result. Secondary endpoints were a prognostic analysis of factors affecting maintenance of MMR at 6 months in learning and validation samples and the cost impact of stopping TKI therapy. We considered loss of haematological response, progress to accelerated-phase chronic myeloid leukaemia, or blast crisis as serious adverse events. This study presents the results of the prespecified interim analysis, which was done after the 6-month molecular relapse-free survival status was known for 200 patients. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01596114. Findings: Between May 30, 2012, and Dec 3, 2014, we assessed 868 patients with chronic myeloid leukaemia for eligibility, of whom 758 were enrolled. Median follow-up of the 755 patients evaluable for molecular response was 27 months (IQR 21–34). Molecular relapse-free survival for these patients was 61% (95% CI 57–64) at 6 months and 50% (46–54) at 24 months. Of these 755 patients, 371 (49%) lost MMR after TKI discontinuation, four (1%) died while in MMR for reasons unrelated to chronic myeloid leukaemia (myocardial infarction, lung cancer, renal cancer, and heart failure), and 13 (2%) restarted TKI therapy while in MMR. A further six (1%) patients died in chronic-phase chronic myeloid leukaemia after loss of MMR and re-initiation of TKI therapy for reasons unrelated to chronic myeloid leukaemia, and two (
- Published
- 2018
13. PF415 EFFICACY AND SAFETY FOLLOWING DOSE REDUCTION OF BOSUTINIB IN PREVIOUSLY TREATED PATIENTS WITH CHRONIC MYELOID LEUKEMIA: ANALYSIS OF THE PHASE 4 BYOND TRIAL
- Author
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Brümmendorf, T.H., primary, Giles, F., additional, Gambacorti-Passerini, C., additional, Roboz, G.J., additional, Le Coutre, P., additional, Hjorth-Hansen, H., additional, Stenke, L., additional, Cervantes, F., additional, Rousselot, P., additional, Viqueira, A., additional, Bardy-Bouxin, N., additional, Leip, E., additional, Leone, J.M., additional, Steegmann, J.L., additional, Cortes, J.E., additional, and Hochhaus, A., additional
- Published
- 2019
- Full Text
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14. Corrections to “Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”
- Author
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Hochhaus, A., primary, Saussele, S., additional, Rosti, G., additional, Mahon, F.-X., additional, Janssen, J.J.W.M, additional, Hjorth-Hansen, H., additional, Richter, J., additional, and Buske, C., additional
- Published
- 2018
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15. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia
- Author
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Ilander, M, primary, Olsson-Strömberg, U, additional, Schlums, H, additional, Guilhot, J, additional, Brück, O, additional, Lähteenmäki, H, additional, Kasanen, T, additional, Koskenvesa, P, additional, Söderlund, S, additional, Höglund, M, additional, Markevärn, B, additional, Själander, A, additional, Lotfi, K, additional, Dreimane, A, additional, Lübking, A, additional, Holm, E, additional, Björeman, M, additional, Lehmann, S, additional, Stenke, L, additional, Ohm, L, additional, Gedde-Dahl, T, additional, Majeed, W, additional, Ehrencrona, H, additional, Koskela, S, additional, Saussele, S, additional, Mahon, F-X, additional, Porkka, K, additional, Hjorth-Hansen, H, additional, Bryceson, Y T, additional, Richter, J, additional, and Mustjoki, S, additional
- Published
- 2016
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16. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia
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Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM, Moiraghi B, Perez M, Greil R, Valent P, Bosly A, Martiat P, Noens L, André M, Verhoef G, Conchon M, Souza C, Nonino A, Hungria V, Zanichelli MA, Colturato V, Forrest D, Lipton JH, Savoie ML, Delage R, Lalancette M, Quintero G, Gomez M, Klamova H, Faber E, Bjerrum OW, Fredriksen H, Vestergaard H, Marcher C, Kamel H, Elzawam H, Porkka K, Remes K, Reiffers J, Guilhot F, Facon T, Tulliez M, Guerci Bresler AP, Nicolini FE, Charbonnier A, Rea D, Johnson Ansah A, Legros L, Harousseau JL, Rigal Huguet F, Escoffre M, Gardembas M, Guyotat D, Cahn JY, Gattermann N, Ottmann O, Niederwieser D, Stegelmann F, Schafhausen P, Brümmendorf T, Duyster J, Blumenstengel K, Scheid C, Kneba M, Kwong YL, Masszi T, Petrini M, Alimena G, Di Raimondo F, Rosti G, Rotoli B, Pungolino E, Amadori S, Abruzzese E, Fioritoni G, Lauria F, Bosi A, Martelli M, Rambaldi A, Ferrara F, Nobile F, Gobbi M, Carella AM, Orlandi EM, Leoni P, Tiribelli M, Levis A, Imamura M, Takahashi N, Tsukamoto N, Chiba S, Nagai T, Okamoto S, Miura O, Kurokawa M, Ohnishi K, Toba K, Nakao S, Tomita A, Miyamura K, Hino M, Maeda Y, Kimura A, Kawaguchi T, Miyazaki Y, Nakaseko C, Jinnai I, Matsuda A, Matsumura I, Ishikawa J, Ohyashiki K, Okada M, Usuki K, Kobayashi Y, Ohishi K, Imai K, Miyawaki S, Kanda Y, Park SY, Kim HJ, Sohn SK, Lee KH, Jung CW, Ong TC, Gómez Almaguer D, Kassack J, Ossenkoppele GJ, Gedde Dahl T, Hjorth Hansen H, Jedrzejczak W, Dmoszynska A, Starzak Dwozdz J, Holowiecki J, Kyrcz Krzemieñ S, Kuliczkowski K, Zaritsky A, Turkina A, Pospelova T, Goh YT, Koh LP, Demitrovicova L, Mistrik M, Ruff P, Louw V, Dreosti LM, Novitzky N, Cohen G, Cervantes F, Cañizo C, de Paz R, del Castillo S, Perez Encinas M, Sanz Alonso M, Marin F, Pérez López R, Hernandez Boluda J, Echeveste Gutierrez MA, Odriozola J, Herrera P, Steegman JL, Conde E, Lopez P, Giraldo P, Boque C, Heredia B, Font AJ, Rodriguez RF, Rodriguez MJ, Batlle J, Stenke L, Lehmann S, Wadenvik H, Simonsson B, Markevärn B, Själander A, Richter J, Bjoreman M, Eriksson KM, Chalandon Y, Shih LY, Yao M, Wang MC, Jootar S, Bunworasate U, Ulkü B, Haznedar R, Undar B, Sahin B, Marin D, Smith G, Byrne J, Holyoake T, Kalaycio M, Akard L, Heaney M, Al Janadi A, Goldberg S, Powell B, Harker WG, Shea T, Gingrich R, Glass J, Paquette R, Siegrist C, Woodson M, Fehrenbacher L, Koh H, Flinn I, Arrowsmith E, Ervin T, Guerra M, Wallach H, Berry W, Burke J, Edenfield W, Guzley G, Davis J, Richards D, Schlossman D, Kolibaba K, Alemany C, Savin M, Robbins G, Lopez J, Goldman JM, Camm J, Schiffer CA, Sargent D.J., PANE, FABRIZIO, Saglio, G, Kim, Dw, Issaragrisil, S, le Coutre, P, Etienne, G, Lobo, C, Pasquini, R, Clark, Re, Hochhaus, A, Hughes, Tp, Gallagher, N, Hoenekopp, A, Dong, M, Haque, A, Larson, Ra, Kantarjian, Hm, Moiraghi, B, Perez, M, Greil, R, Valent, P, Bosly, A, Martiat, P, Noens, L, André, M, Verhoef, G, Conchon, M, Souza, C, Nonino, A, Hungria, V, Zanichelli, Ma, Colturato, V, Forrest, D, Lipton, Jh, Savoie, Ml, Delage, R, Lalancette, M, Quintero, G, Gomez, M, Klamova, H, Faber, E, Bjerrum, Ow, Fredriksen, H, Vestergaard, H, Marcher, C, Kamel, H, Elzawam, H, Porkka, K, Remes, K, Reiffers, J, Guilhot, F, Facon, T, Tulliez, M, Guerci Bresler, Ap, Nicolini, Fe, Charbonnier, A, Rea, D, Johnson Ansah, A, Legros, L, Harousseau, Jl, Rigal Huguet, F, Escoffre, M, Gardembas, M, Guyotat, D, Cahn, Jy, Gattermann, N, Ottmann, O, Niederwieser, D, Stegelmann, F, Schafhausen, P, Brümmendorf, T, Duyster, J, Blumenstengel, K, Scheid, C, Kneba, M, Kwong, Yl, Masszi, T, Petrini, M, Alimena, G, Di Raimondo, F, Rosti, G, Rotoli, B, Pane, Fabrizio, Pungolino, E, Amadori, S, Abruzzese, E, Fioritoni, G, Lauria, F, Bosi, A, Martelli, M, Rambaldi, A, Ferrara, F, Nobile, F, Gobbi, M, Carella, Am, Orlandi, Em, Leoni, P, Tiribelli, M, Levis, A, Imamura, M, Takahashi, N, Tsukamoto, N, Chiba, S, Nagai, T, Okamoto, S, Miura, O, Kurokawa, M, Ohnishi, K, Toba, K, Nakao, S, Tomita, A, Miyamura, K, Hino, M, Maeda, Y, Kimura, A, Kawaguchi, T, Miyazaki, Y, Nakaseko, C, Jinnai, I, Matsuda, A, Matsumura, I, Ishikawa, J, Ohyashiki, K, Okada, M, Usuki, K, Kobayashi, Y, Ohishi, K, Imai, K, Miyawaki, S, Kanda, Y, Park, Sy, Kim, Hj, Sohn, Sk, Lee, Kh, Jung, Cw, Ong, Tc, Gómez Almaguer, D, Kassack, J, Ossenkoppele, Gj, Gedde Dahl, T, Hjorth Hansen, H, Jedrzejczak, W, Dmoszynska, A, Starzak Dwozdz, J, Holowiecki, J, Kyrcz Krzemieñ, S, Kuliczkowski, K, Zaritsky, A, Turkina, A, Pospelova, T, Goh, Yt, Koh, Lp, Demitrovicova, L, Mistrik, M, Ruff, P, Louw, V, Dreosti, Lm, Novitzky, N, Cohen, G, Cervantes, F, Cañizo, C, de Paz, R, del Castillo, S, Perez Encinas, M, Sanz Alonso, M, Marin, F, Pérez López, R, Hernandez Boluda, J, Echeveste Gutierrez, Ma, Odriozola, J, Herrera, P, Steegman, Jl, Conde, E, Lopez, P, Giraldo, P, Boque, C, Heredia, B, Font, Aj, Rodriguez, Rf, Rodriguez, Mj, Batlle, J, Stenke, L, Lehmann, S, Wadenvik, H, Simonsson, B, Markevärn, B, Själander, A, Richter, J, Bjoreman, M, Eriksson, Km, Chalandon, Y, Shih, Ly, Yao, M, Wang, Mc, Jootar, S, Bunworasate, U, Ulkü, B, Haznedar, R, Undar, B, Sahin, B, Marin, D, Smith, G, Byrne, J, Holyoake, T, Kalaycio, M, Akard, L, Heaney, M, Al Janadi, A, Goldberg, S, Powell, B, Harker, Wg, Shea, T, Gingrich, R, Glass, J, Paquette, R, Siegrist, C, Woodson, M, Fehrenbacher, L, Koh, H, Flinn, I, Arrowsmith, E, Ervin, T, Guerra, M, Wallach, H, Berry, W, Burke, J, Edenfield, W, Guzley, G, Davis, J, Richards, D, Schlossman, D, Kolibaba, K, Alemany, C, Savin, M, Robbins, G, Lopez, J, Goldman, Jm, Camm, J, Schiffer, Ca, and Sargent, D. J.
- Published
- 2010
17. Implementation of a standardised method for the production of allogeneic serum eye drops from regular blood donors in a Norwegian University Hospital: Some methodological aspects and clinical considerations
- Author
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Espinosa, A., primary, Hjorth-Hansen, H., additional, Aasly, K., additional, Teigum, I., additional, Sivertsen, G., additional, and Seghatchian, J., additional
- Published
- 2015
- Full Text
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18. IL1RAP expression as a measure of leukemic stem cell burden at diagnosis of chronic myeloid leukemia predicts therapy outcome
- Author
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Landberg, N, primary, Hansen, N, additional, Askmyr, M, additional, Ågerstam, H, additional, Lassen, C, additional, Rissler, M, additional, Hjorth-Hansen, H, additional, Mustjoki, S, additional, Järås, M, additional, Richter, J, additional, and Fioretos, T, additional
- Published
- 2015
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19. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment ofhigh-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNetStudy
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Baccarani, M, Rosti, G, Castagnetti, F, Haznedaroglu, I, Porkka, K, Abruzzese, E, Alimena, G, Ehrencrona, H, Hjorth Hansen, H, Kairisto, V, Levato, L, Martinelli, G, Nagler, A, Lanng Nielsen, J, Ozbek, U, Palandri, F, Palmieri, F, Pane, F, Rege Cambrin, G, Russo, D, Specchia, G, Testoni, N, Weiss Bjerrum, O, Saglio, Giuseppe, and Simonsson, B.
- Published
- 2009
20. A comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of patients with high risk, Ph-pos, chronic myeloid leukemia. An ELN Study
- Author
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Baccarani, M., Rosti, G., Castagnetti, F., Haznedaroglu, I., Porkka, K., Abruzzese, E., Alimena, G., Amabile, M., Boström, H., Hjorth Hansen, H., Kairisto, V., Levato, L., Martinelli, G., Nagler, A., Lanng Nielsen, J., Ozbek, U., Palandri, F., Palmieri, F., Pane, F., Rege Cambrin, G., Russo, Domenico, Specchia, G., Testoni, N., Weiss Bjerrum, O., Saglio, G., and Simonsson, B.
- Published
- 2009
21. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia
- Author
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Ilander, M, Olsson-Strömberg, U, Schlums, H, Guilhot, J, Brück, O, Lähteenmäki, H, Kasanen, T, Koskenvesa, P, Söderlund, S, Höglund, M, Markevärn, B, Själander, A, Lotfi, K, Dreimane, A, Lübking, A, Holm, E, Björeman, M, Lehmann, S, Stenke, L, Ohm, L, Gedde-Dahl, T, Majeed, W, Ehrencrona, H, Koskela, S, Saussele, S, Mahon, F-X, Porkka, K, Hjorth-Hansen, H, Bryceson, Y T, Richter, J, and Mustjoki, S
- Abstract
Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56brightNK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.
- Published
- 2017
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22. Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia
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Hjorth-Hansen, H., primary, Seidel, C., additional, Lamvik, J., additional, Börset, M., additional, Sundan, A., additional, and Wagge, A., additional
- Published
- 2009
- Full Text
- View/download PDF
23. Safety and efficacy of the combination of pegylated interferon-a2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients
- Author
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Hjorth-Hansen, H, Stentoft, J, Richter, J, Koskenvesa, P, Höglund, M, Dreimane, A, Porkka, K, Gedde-Dahl, T, Gjertsen, B T, Gruber, F X, Stenke, L, Eriksson, K M, Markevärn, B, Lübking, A, Vestergaard, H, Udby, L, Bjerrum, O W, Persson, I, Mustjoki, S, and Olsson-Strömberg, U
- Abstract
Dasatinib (DAS) and interferon-a have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100?mg o.d. followed by addition of pegylated interferon-a2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15?µg/week and it increased to 25?µg/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR4was achieved by 46% and MR4.5by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS±PegIFN is warranted.
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- 2016
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24. Hepatocyte growth factor and its receptor c-met in multiple myeloma
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Borset, M, primary, Hjorth-Hansen, H, additional, Seidel, C, additional, Sundan, A, additional, and Waage, A, additional
- Published
- 1996
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25. Role of hepatocyte growth factor and its receptor c-met in multiple myeloma.
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Seidel, Carina, Børset, Magne, Hjorth-Hansen, Henrik, Sundan, Anders, Waage, Anders, Seidel, C, Børset, M, Hjorth-Hansen, H, Sundan, A, and Waage, A
- Abstract
Multiple myeloma is characterised by the clonal expansion of malignant plasma cells. Recently, we reported that a new cytokine, hepatocyte growth factor (HGF), and its receptor c-met are related to this disease. Here we review the observations that associate HGF with myeloma. Malignant plasma cells produce HGF and express the receptor c-met. Many patients have elevated HGF levels, which is unfavourable both in terms of survival and response to treatment. Possible biological roles of HGF in this disease are discussed, with special focus on bone homeostasis and its binding to heparan sulphate proteoglycans. [ABSTRACT FROM AUTHOR]
- Published
- 1998
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26. ASSESSMENT OF THERAPY RESPONSE IN CHRONIC MYELOID LEUKEMIA VIA 1 MONTH BCR-ABL1 TRANSCRIPT DECLINE
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El Missiry, M., Hjorth-Hansen, H., Richter, J., Olson-Stromberg, U., Stenke, L., Kimmo Porkka, Kreutzmann, A., and Satu Maarit Mustjoki
27. STOPPING TYROSINE KINASE INHIBITORS IN A VERY LARGE COHORT OF EUROPEAN CHRONIC MYELOID LEUKEMIA PATIENTS
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Richter, J., Mahon, F. X., Guilhot, J., Hjorth-Hansen, H., Almeida, A., Janssen, J. J., Mayer, J., Kimmo Porkka, Panayiotidis, P., Olsson-Stromberg, U., Berger, M. G., Diamond, J., Ehrencrona, H., Kairisto, V., Machova Polakova, K., Muller, M. C., Satu Maarit Mustjoki, Hochhaus, A., Pfirrmann, M., and Saussele, S.
28. Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma
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Therese Standal, Hjorth-Hansen H, Rasmussen T, Im, Dahl, Lenhoff S, At, Brenne, Seidel C, Baykov V, Waage A, Børset M, Sundan A, and Hjertner O
29. TELOMERE SHORTENING IN CD34+38-BCR-ABL POSITIVE BONE MARROW CELLS FROM NEWLY DIAGNOSED PATIENTS WITH CML CORRELATES WITH THE CLONE SIZE OF THE LEUKEMIC STEM CELL COMPARTMENT
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Bouillon, A. -S, Ferreira, M. Ventura, Awad, S. A., Richter, J., Hjorth-Hansen, H., Hummel, S., Mirle Schemionek, Mustjoki, S., Beier, F., and Bruemmendorf, T. H.
30. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia
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Simona Soverini, Jeffrey H. Lipton, Richard A. Larson, Dietger Niederwieser, Andrey Zaritskey, Fabrizio Pane, Francois-Xavier Mahon, Jeroen Janssen, Richard E. Clark, François Guilhot, Juan Luis Steegmann, Jerald P. Radich, Michael W. Deininger, Andreas Hochhaus, Richard T. Silver, Susanne Saußele, Johan Richter, Timothy P. Hughes, Jane F. Apperley, Jiří Mayer, Henrik Hjorth-Hansen, Hagop M. Kantarjian, Jorge E. Cortes, Anna G. Turkina, Michele Baccarani, Gianantonio Rosti, Franck E. Nicolini, Philippe Rousselot, Giuseppe Saglio, Delphine Rea, Dong-Wook Kim, Ruediger Hehlmann, Charles A. Schiffer, Francisco Cervantes, Hochhaus A., Baccarani M., Silver R.T., Schiffer C., Apperley J.F., Cervantes F., Clark R.E., Cortes J.E., Deininger M.W., Guilhot F., Hjorth-Hansen H., Hughes T.P., Janssen J.J.W.M., Kantarjian H.M., Kim D.W., Larson R.A., Lipton J.H., Mahon F.X., Mayer J., Nicolini F., Niederwieser D., Pane F., Radich J.P., Rea D., Richter J., Rosti G., Rousselot P., Saglio G., Saussele S., Soverini S., Steegmann J.L., Turkina A., Zaritskey A., Hehlmann R., Hochhaus, A., Baccarani, M., Silver, R. T., Schiffer, C., Apperley, J. F., Cervantes, F., Clark, R. E., Cortes, J. E., Deininger, M. W., Guilhot, F., Hjorth-Hansen, H., Hughes, T. P., Janssen, J. J. W. M., Kantarjian, H. M., Kim, D. W., Larson, R. A., Lipton, J. H., Mahon, F. X., Mayer, J., Nicolini, F., Niederwieser, D., Pane, F., Radich, J. P., Rea, D., Richter, J., Rosti, G., Rousselot, P., Saglio, G., Saussele, S., Soverini, S., Steegmann, J. L., Turkina, A., Zaritskey, A., Hehlmann, R., Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Bergonié [Bordeaux], UNICANCER, Centre Léon Bérard [Lyon], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Novartis Berlin Mathematical School, BMS Daiichi-Sankyo Janssen Pharmaceuticals Angelini Pharma Pfizer, The ELN panel for recommendations in CML comprises 34 experts from Europe, America, and the Asian-Pacific areas. The panel met six times at international meetings of the American Society of Hematology (2015, 2016), the European School of Hematology (2017), the ELN (2019), the European Investigators on CML (2019), and the European School of Hematology/International CML Foundation (2019). Five sets of key questions were submitted to panel members to complement the meetings. Discordant opinions were harmonized by email discussions, and a consensus of 75–100% was reached in most, but not all instances. Unresolved controversies are described in the discussion section. The costs of the meetings and the preparation of the interim and final reports were born entirely by ELN, a research network of excellence initiated by the European Union, now funded by donations and projects of ELN participants. There was no financial support from industry for any activity. Treatment recommendations are limited to the TKIs that have been approved with at least one indication in CML, either by the US Federal Drug Administration (FDA) or/and by the European Medicine Agency (EMA). The drugs are listed in the order of FDA approval. The panel acknowledges that not all drugs may be available worldwide and that the high price of some makes access to these drugs problematic in some countries., Conflict of interest Members of the expert panel declare the following potential conflicts of interest: AH, Research support: Novartis, BMS, MSD, Pfizer, Incyte. Honoraria: Novartis, BMS, Pfizer, Incyte, Takeda, Fusion Pharma. MB, Honoraria: Novartis, BMS, Pfizer, Incyte, Ariad, Takeda, Fusion Pharma. Logistic support: Novartis, BMS, Pfizer, Incyte, Ariad. CS, Research support: Ariad. Honoraria: Novartis, Teva, Pfizer, Juno, Astellas, Ambit. JFA, Research support: Incyte, Novartis, Pfizer. Honoraria: Incyte, Novartis, Pfizer, BMS. FC, Honoraria: Novartis, BMS, Pfizer, Incyte, Celgene, Italfarmaco. Travel grants: BMS, Celgene. REC, Research support: Novartis, Pfizer, BMS. Honoraria: Novartis, Pfizer, BMS, Ariad/Incyte, Jazz, Abbvie. JEC, Research support: BMS, Novartis, Pfizer, Sun Pharma, Takeda. Honoraria: Novartis, Pfizer, Takeda. MWD, Research support: Takeda, Novartis, Pfizer, Incyte, SPARC, TetraLogic Pharmaceuticals, Blueprint. Honoraria: Blueprint, Fusion Pharma, Novartis, Sangamo, Ascentage Pharma, Adelphi, CTI, BMS, Pfizer, Takeda, Medscape, Incyte, Humana, TRM, Ariad, Galena Biopharma. FG, Research support: Novartis, Roche. Honoraria: Novartis, BMS, Celgene. HHH, Research support: Pfizer, BMS, Merck, Austrian Orphan Pharma, Nordic Cancer Union. Honoraria: Pfizer, Incyte, Austrian Orphan Pharma. TPH, Research support: Novartis, BMS, Celgene. Honoraria: Novartis, BMS, Fusion Pharma. Travel grants: Novartis. JJ, Research support: Novartis, BMS. President, Apps for Care and Science, nonprofit foundation supported by Daiichi-Sankyo, Janssen, Incyte, BMS, Servier, Jazz, Celgene. Honoraria: Abbvie, Novartis, Pfizer, Incyte. HMK, Research support: AbbVie, Agios, Amgen, Ariad, Astex, BMS, Cyclacel, Daiichi-Sankyo, Immunogen, Jazz Pharma, Novartis, Pfizer. Honoraria: AbbVie, Actinium, Agios, Amgen, Immunogen, Pfizer, Takeda. DWK, Research support: Novartis, Pfizer, BMS, Takeda, Il-Yang Co. Honoraria: Novartis, BMS, Otsuka, Il-Yang Co. RAL, Research support: Astellas, Celgene, Cellectis, Daiichi Sankyo, Novartis, Rafael Pharmaceuticals. Honoraria: Amgen, Celgene, CVS Caremark, Epizyme, Novartis, Takeda. JHL, Research support and honoraria: Novartis, BMS, Pfizer, Takeda. FXM, Research support and honoraria: Novartis. Travel grants: Celgene, Pfizer, Astra Zeneca. JM, Research support: Angelini, Pfizer, Novartis, BMS. Travel grants: Novartis. FN, Research support: Novartis, Incyte. Honoraria: Incyte biosciences, Novartis, BMS, Sun Pharma. Travel grants: Incyte biosciences, Novartis, BMS. DN, Research support: Daiichi, Honoraria: Cellectis. Travel grants: EUSA, Novartis, and Amgen. FP, Research support: Novartis. Honoraria: Novartis, BMS, Pfizer, Incyte. JPR, Research support: Novartis. Honoraria: Novartis, BMS, Ariad, Amgen, Takeda, Cepheid, Bio-Rad, Adaptive, Seagen, Gilead. DR, Honoraria: BMS, Novartis, Pfizer, Incyte. JR, Honoraria: Novartis, Pfizer. GR, Research support, honoraria, and travel grants: Novartis, BMS, Incyte, Pfizer, Roche. PR, Research support: Incyte, Pfizer. Honoraria: BMS, Incyte, Pfizer, Novartis. GS, Honoraria: Novartis, BMS, Incyte, Pfizer. SiS, Honoraria: Incyte. SuS, Research support: BMS, Incyte, Novartis. Honoraria: BMS, Incyte, Novartis, Pfizer. Travel grants: BMS, Incyte, Novartis. JLS, Research support, honoraria, and travel grants: BMS, Incyte, Novartis, Pfizer. AT, Honoraria: BMS, Novartis, Pfizer, Fusion Pharma. Travel grants: BMS, Novartis, Pfizer. AZ, Research support: Novartis, Celgene, Janssen. Travel grants: Novartis. RTS, RH, none.
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Oncology ,Cancer Research ,Consensus Development Conferences as Topic ,Dasatinib ,Fusion Proteins, bcr-abl ,Quinoline ,Gene Expression ,Review Article ,Tyrosine-kinase inhibitor ,Antineoplastic Agent ,European LeukemiaNet ,0302 clinical medicine ,hemic and lymphatic diseases ,0303 health sciences ,Aniline Compounds ,Myeloid leukemia ,Disease Management ,Hematology ,Aniline Compound ,3. Good health ,030220 oncology & carcinogenesis ,Quinolines ,Imatinib Mesylate ,Bosutinib ,Nitrile ,medicine.drug ,Human ,medicine.medical_specialty ,medicine.drug_class ,Clinical Decision-Making ,Protein Kinase Inhibitor ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Targeted therapies ,Life Expectancy ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Nitriles ,medicine ,Humans ,Protein Kinase Inhibitors ,Chronic myeloid leukaemia ,030304 developmental biology ,Monitoring, Physiologic ,business.industry ,Imatinib ,Survival Analysis ,Discontinuation ,Pyrimidines ,Nilotinib ,Pyrimidine ,Quality of Life ,business - Abstract
The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
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- 2020
31. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013
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Timothy P. Hughes, Martin C. Müller, Michael W. Deininger, Philippe Rousselot, Richard A. Larson, Michele Baccarani, Richard E. Clark, Fabrizio Pane, Andreas Hochhaus, Richard T. Silver, Henrik Hjorth-Hansen, Giuseppe Saglio, Jiri Mayer, Giovanni Martinelli, Jeffrey H. Lipton, Charles A. Schiffer, Dietger Niederwieser, Jerald P. Radich, Jane F. Apperley, Susanne Saußele, Gianantonio Rosti, Bengt Simonsson, François Guilhot, Francisco Cervantes, Simona Soverini, John M. Goldman, François Xavier Mahon, Juan Luis Steegmann, Rüdiger Hehlmann, Dong-Wook Kim, Hagop M. Kantarjian, Jorge E. Cortes, Baccarani, M, Deininger, Mw, Rosti, G, Hochhaus, A, Soverini, S, Apperley, Jf, Cervantes, F, Clark, Re, Cortes, Je, Guilhot, F, Hjorth Hansen, H, Hughes, Tp, Kantarjian, Hm, Kim, Dw, Larson, Ra, Lipton, Jh, Mahon, Fx, Martinelli, G, Mayer, J, M?ller, Mc, Niederwieser, D, Pane, Fabrizio, Radich, Jp, Rousselot, P, Saglio, G, Sau?ele, S, Schiffer, C, Silver, R, Simonsson, B, Steegmann, Jl, Goldman, Jm, Hehlmann, R., Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saußele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R., University of Bologna, University of Utah, and Université de Poitiers
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polymerase chain reaction ,Fusion Proteins, bcr-abl ,Review Article ,protein-tyrosine kinase inhibitor ,Biochemistry ,Piperazines ,cytogenetics ,chemistry.chemical_compound ,European LeukemiaNet ,0302 clinical medicine ,imatinib mesylate ,hemic and lymphatic diseases ,dasatinib ,BCR-ABL ,Randomized Controlled Trials as Topic ,0303 health sciences ,withdrawing treatment ,Ponatinib ,leukemia ,Myeloid leukemia ,Hematology ,Prognosis ,3. Good health ,Europe ,chronic ,Dasatinib ,Treatment Outcome ,030220 oncology & carcinogenesis ,Benzamides ,medicine.drug ,medicine.medical_specialty ,myelocytic ,Immunology ,Antineoplastic Agents ,second line treatment ,03 medical and health sciences ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,TYROSINE KINASE INHIBITORS ,Humans ,nilotinib ,030304 developmental biology ,allogeneic stem cell transplant ,business.industry ,Cell Biology ,Discontinuation ,Transplantation ,Thiazoles ,Pyrimidines ,Imatinib mesylate ,Nilotinib ,chemistry ,business ,CHRONIC MYELOID LEUKEMIA (CML) ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Stem Cell Transplantation ,transplantation - Abstract
Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, 10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome–positive [Ph+] >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
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- 2013
32. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: A European LeukemiaNet Study
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Luciano Levato, Ugur Ozbek, Elisabetta Abruzzese, Henrik Hjorth-Hansen, Fausto Castagnetti, Giovanna Rege-Cambrin, Nicoletta Testoni, Francesca Palandri, Domenico Russo, Giovanni Martinelli, Michele Baccarani, Johann Lanng Nielsen, Veli Kairisto, Giuseppe Saglio, Giuliana Alimena, Fabrizio Pane, Fausto Palmieri, Arnon Nagler, Gianantonio Rosti, Bengt Simonsson, Ibrahim C. Haznedaroglu, Kimmo Porkka, Giorgina Specchia, Ole Weiss-Bjerrum, Hans Ehrencrona, Baccarani, M, Rosti, G, Castagnetti, F, Haznedaroglu, I, Porkka, K, Abruzzese, E, Alimena, G, Ehrencrona, H, Hjorth Hansen, H, Kairisto, V, Levato, L, Martinelli, G, Nagler, A, Lanng Nielsen, J, Ozbek, U, Palandri, F, Palmieri, F, Pane, Fabrizio, Rege Cambrin, G, Russo, D, Specchia, G, Testoni, N, Weiss Bjerrum, O, Saglio, G, Simonsson, B., Baccarani M, Rosti G, Castagnetti F, Haznedaroglu I, Porkka K, Abruzzese E, Alimena G, Ehrencrona H, Hjorth-Hansen H, Kairisto V, Levato L, Martinelli G, Nagler A, Nielsen JL, Ozbek U, Palandri F, Palmieri F, Pane F, Rege-Cambrin G, Russo D, Specchia G, Testoni N, Weiss-Bjerrum O, Saglio G, and Simonsson B.
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Male ,bcr-abl ,Fusion Proteins, bcr-abl ,Biochemistry ,Gastroenterology ,Piperazines ,Risk Factors ,80 and over ,Chronic ,Aged, 80 and over ,CHRONIC MYELOGENOUS LEUKEMIA, BCR-ABL TRANSCRIPTS, HARMONIZING CURRENT METHODOLOGY, TYROSINE KINASE INHIBITORS, MAJOR MOLECULAR RESPONSES, STANDARD-DOSE IMATINIB, CHRONIC-PHASE, CML PATIENTS, CYTOGENETIC RESPONSES, INTERFERON-ALPHA ,Leukemia ,HARMONIZING CURRENT METHODOLOGY ,Standard treatment ,CHRONIC MYELOGENOUS LEUKEMIA ,Myeloid leukemia ,Hematology ,Middle Aged ,Protein-Tyrosine Kinases ,Prognosis ,BCR-ABL TRANSCRIPTS ,Europe ,Survival Rate ,CYTOGENETIC RESPONSES ,Treatment Outcome ,Benzamides ,Cytogenetic Analysis ,Imatinib Mesylate ,MAJOR MOLECULAR RESPONSES ,Female ,Drug ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Alpha interferon ,Aged ,Dose-Response Relationship, Drug ,Humans ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Protein Kinase Inhibitors ,Pyrimidines ,Young Adult ,CML PATIENTS ,Dose-Response Relationship ,Internal medicine ,TYROSINE KINASE INHIBITORS ,medicine ,IMATINIB MESYLATE (IM) ,Survival rate ,CHRONIC MYELOID LEUKEMIA ,CHRONIC-PHASE ,business.industry ,Fusion Proteins ,Imatinib ,Cell Biology ,medicine.disease ,Imatinib mesylate ,Endocrinology ,STANDARD-DOSE IMATINIB ,BCR-ABL Positive ,INTERFERON-ALPHA ,business ,Chronic myelogenous leukemia ,Myelogenous - Abstract
Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph+ CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.
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- 2009
33. Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders
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Mohammad K. Eldomery, Olaug K. Rødningen, Cecilia Poli, Debra Canter, Berit Flatø, Ketil Heimdal, Nicholas L. Rider, Silje F. Jørgensen, Hasibe Artac, Hans Christian Erichsen, Francisco Javier Espinosa Rosales, Ivan K. Chinn, Alison A. Bertuch, Bo Yuan, Jordan S. Orange, Emily M. Mace, Wojciech Wiszniewski, Robert Lyle, Shalini N. Jhangiani, Tobias Gedde-Dahl, Carla M. Davis, Carl E. Allen, I. Celine Hanson, Magnus K. O. Burstedt, Thomas B. Issekutz, Mari Ann Kulseth, Yavuz Bayram, Eric A. Smith, Tram N. Cao, Stephen Jolles, Andrew C. Issekutz, Pubudu S. Samarakoon, Alice Y. Chan, Gozde Yesil, Eva Holmberg, Børre Fevang, Diana K. Bayer, John W. Belmont, Asbjørg Stray-Pedersen, Timothy J. Vece, Magdalena Walkiewicz, James R. Lupski, Ying Sheng, Trine Prescott, Liv T. N. Osnes, Cecilie F. Rustad, Nina Denisse Guerrero-Cursaru, Juan Carlos Aldave Becerra, Victor Wei Zhang, Philip M. Boone, Mohammad S. Ehlayel, Jason W. Caldwell, Tore G. Abrahamsen, José Luis Franco, Harshal Abhyankar, Henrik Hjorth-Hansen, Liliana Bezrodnik, Vegard Skogen, Nicola A.M. Wright, Lisa R. Forbes, Anne Grete Bechensteen, Christine R. Beck, Saul Oswaldo Lugo Reyes, Lee-Jun C. Wong, Shen Gu, Sarah K. Nicholas, Christina E. West, Filiz O. Seeborg, Mehmed M. Atik, Eric Boerwinkle, Luis A. Pedroza, Caterina Cancrini, Hanne Sørmo Sorte, Yaping Yang, Christine M. Eng, Richard A. Gibbs, Lenora M. Noroski, Alessandro Aiuti, Ender Karaca, Torstein Øverland, Claudia Milena Trujillo Vargas, Jordan K. Abbott, Geir E. Tjønnfjord, William T. Shearer, Javier Chinen, Ingunn Dybedal, Tomasz Gambin, Donna M. Muzny, Pål Aukrust, Ingvild Nordøy, María Soledad Caldirola, Jianhong Hu, Zeynep Coban Akdemir, YEŞİL, Gözde, Stray Pedersen, A, Sorte, H, Samarakoon, P, Gambin, T, Chinn, Ik, Coban Akdemir, Zh, Erichsen, Hc, Forbes, Lr, Gu, S, Yuan, B, Jhangiani, Sn, Muzny, Dm, Rødningen, Ok, Sheng, Y, Nicholas, Sk, Noroski, Lm, Seeborg, Fo, Davis, Cm, Canter, Dl, Mace, Em, Vece, Tj, Allen, Ce, Abhyankar, Ha, Boone, Pm, Beck, Cr, Wiszniewski, W, Fevang, B, Aukrust, P, Tjønnfjord, Ge, Gedde Dahl, T, Hjorth Hansen, H, Dybedal, I, Nordøy, I, Jørgensen, Sf, Abrahamsen, Tg, Øverland, T, Bechensteen, Ag, Skogen, V, Osnes, Lt, Kulseth, Ma, Prescott, Te, Rustad, Cf, Heimdal, Kr, Belmont, Jw, Rider, Nl, Chinen, J, Cao, Tn, Smith, Ea, Caldirola, M, Bezrodnik, L, Lugo Reyes, So, Espinosa Rosales, Fj, Guerrero Cursaru, Nd, Pedroza, La, Poli, Cm, Franco, Jl, Trujillo Vargas, Cm, Aldave Becerra, Jc, Wright, N, Issekutz, Tb, Issekutz, Ac, Abbott, J, Caldwell, Jw, Bayer, Dk, Chan, Ay, Aiuti, Alessandro, Cancrini, C, Holmberg, E, West, C, Burstedt, M, Karaca, E, Yesil, G, Artac, H, Bayram, Y, Atik, Mm, Eldomery, Mk, Ehlayel, M, Jolles, S, Flatø, B, Bertuch, Aa, Hanson, Ic, Zhang, Vw, Wong, Lj, Hu, J, Walkiewicz, M, Yang, Y, Eng, Cm, Boerwinkle, E, Gibbs, Ra, Shearer, Wt, Lyle, R, Orange, J, Lupski, J. R., and Selçuk Üniversitesi
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0301 basic medicine ,Male ,Allergy ,Genomic approaches delineate heterogeneous Mendelian disorders-, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, cilt.139, ss.232-245, 2017 [Stray-Pedersen A., Sorte H. S. , Samarakoon P., Gambin T., Chinn I. K. , Akdemir Z. H. C. , Erichsen H. C. , Forbes L. R. , Gu S., Yuan B., et al., -Primary immunodeficiency diseases] ,0302 clinical medicine ,OMIM : Online Mendelian Inheritance in Man ,Immunology and Allergy ,2.1 Biological and endogenous factors ,Copy-number variation ,Primary immunodeficiency disease ,whole-exome sequencing ,Aetiology ,Child ,Exome sequencing ,Genetics ,screening and diagnosis ,food and beverages ,High-Throughput Nucleotide Sequencing ,Genomics ,Middle Aged ,Settore MED/38 ,Detection ,030220 oncology & carcinogenesis ,Child, Preschool ,Medical genetics ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,DNA Copy Number Variations ,Immunology ,Biology ,03 medical and health sciences ,Young Adult ,Rare Diseases ,Clinical Research ,medicine ,Humans ,Genetic Testing ,Preschool ,Aged ,Severe combined immunodeficiency ,Genetic heterogeneity ,Common variable immunodeficiency ,Prevention ,fungi ,Human Genome ,Immunologic Deficiency Syndromes ,Infant ,medicine.disease ,4.1 Discovery and preclinical testing of markers and technologies ,030104 developmental biology ,Good Health and Well Being ,Primary immunodeficiency ,copy number variants - Abstract
WOS: 000393996800025, PubMed: 27577878, Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes., South-Eastern Norway Health Authority; American Women's club of Oslo; National Human Genome Research InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI); National Heart, Lung, and BloodUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [U54HG006542]; Jeffrey Modell Foundation; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AI-120989], Funding for the work performed in Oslo was provided by the South-Eastern Norway Health Authority, and A. S.-P. received research scholarship from the American Women's club of Oslo. The BHCMG is supported by the National Human Genome Research Institute and the National Heart, Lung, and Blood (U54HG006542). Funding was also provided by the Jeffrey Modell Foundation and NIH AI-120989 (to J.S.O.).
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- 2017
34. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
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Hochhaus, A, Saussele, S, Rosti, G, Mahon, F -X, Janssen, J J W M, Hjorth-Hansen, H, Richter, J, Buske, C, and Committee, ESMO Guidelines
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CHRONIC myeloid leukemia , *TREATMENT of chronic myeloid leukemia - Published
- 2018
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35. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts
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Pierre Laneuville, Vishnu Reddy, Nelson Spector, Nelson Hamerschlak, Eduardo Olavarria, Richard A. Van Etten, Richard E. Clark, Dina Ben Yehuda, Jorge Milone, Ziad Salem, Richard T. Silver, Beatriz Moiraghi, Israel Bendit, David Gómez-Almaguer, Kensuke Usuki, Carmino DeSouza, Raquel Bengió, Madan Jagasia, Anthony P. Schwarer, Ayalew Tefferi, Tetsuzo Tauchi, Güray Saydam, Massimo Breccia, Pankaj Malhotra, Andrew Grigg, Jerald P. Radich, Camille N. Abboud, Moshe Talpaz, Elisabetta Abruzzese, Jenny Byrne, Guillermo J. Ruiz-Argüelles, Daniel J. DeAngelo, Francois-Xavier Mahon, Michael W. Deininger, Philipp le Coutre, Carlos Best, Ryuzo Ohno, Giuseppe Saglio, Jane F. Apperley, José A. López, Eduardo Bullorsky, Christopher Arthur, Richard Stone, Carolina Pavlovsky, Ibrahim C. Haznedaroglu, Ellin Berman, Alfonso Quintás-Cardama, David Marin-Costa, Johan Richter, Jianxiang Wang, Eduardo Cervera, Neil P. Shah, Saengsuree Jootar, Meir Wetzler, Jianda Hu, Richard A. Larson, Alvaro Aguayo, Timothy P. Hughes, Philippe Rousselot, Dragana Milojkovic, Xiao-Jun Huang, Iryna Dyagil, Steven M. Devine, Peter Browett, Vernon J. Louw, Kimmo Porkka, Hossam Kamel, Jesper Stentoft, Qian Jiang, Manuel Ayala, Andrey Zaritskey, Naeem Chaudhri, Muheez A. Durosinmi, John M. Goldman, Anna G. Turkina, Susan O'Brien, Jiri Mayer, Alicia Magarinos, Fawzi Abdel-Rahman, Brian J. P. Huntly, Hugues de Lavallade, Constantine S. Tam, Francisco Cervantes, Tessa L. Holyoake, Amir T. Fathi, Carlo Gambacorti-Passerini, Ekaterina Chelysheva, Adam D. Cohen, Junia V. Melo, Ernesto Fanilla, Tariq I. Mughal, Elias Jabbour, Naoto Takahashi, Itaru Matsumura, Jean Khoury, Paul J. Shami, Charles A. Schiffer, Dong-Wook Kim, Luis Meillon, Bassam Francis Matti, Henrik Hjorth-Hansen, Mahmoud Aljurf, Ali Bazarbachi, Hemant Malhotra, Hagop M. Kantarjian, Giovanni Martinelli, Joseph O. Moore, Jorge E. Cortes, Arnon Nagler, Paolo Vigneri, Ricardo Pasquini, Javier Pinilla-Ibarz, Elza Lomaia, Brian J. Druker, Tapan Saikia, David S. Snyder, Kazunori Ohnishi, Jeffrey H. Lipton, Pia Raanani, Abboud, C, Berman, E, Cohen, A, Cortes, J, Deangelo, D, Deininger, M, Devine, S, Druker, B, Fathi, A, Jabbour, E, Jagasia, M, Kantarjian, H, Khoury, J, Laneuville, P, Larson, R, Lipton, J, Moore, J, Mughal, T, O'Brien, S, Pinilla-Ibarz, J, Quintas-Cardama, A, Radich, J, Reddy, V, Schiffer, C, Shah, N, Shami, P, Silver, R, Snyder, D, Stone, R, Talpaz, M, Tefferi, A, Van Etten, R, Wetzler, M, Abruzzese, E, Apperley, J, Breccia, M, Byrne, J, Cervantes, F, Chelysheva, E, Clark, R, De Lavallade, H, Dyagil, I, Gambacorti-Passerini, C, Goldman, J, Haznedaroglu, I, Hjorth-Hansen, H, Holyoake, T, Huntly, B, Le Coutre, P, Lomaia, E, Mahon, F, Marin-Costa, D, Martinelli, G, Mayer, J, Milojkovic, D, Olavarria, E, Porkka, K, Richter, J, Rousselot, P, Saglio, G, Saydam, G, Stentoft, J, Turkina, A, Vigneri, P, Zaritskey, A, Aguayo, A, Ayala, M, Bendit, I, Bengio, R, Best, C, Bullorsky, E, Cervera, E, Desouza, C, Fanilla, E, Gomez-Almaguer, D, Hamerschlak, N, Lopez, J, Magarinos, A, Meillon, L, Milone, J, Moiraghi, B, Pasquini, R, Pavlovsky, C, Ruiz-Arguelles, G, Spector, N, Arthur, C, Browett, P, Grigg, A, Jianda, H, Huang, X, Hughes, T, Jiang, Q, Jootar, S, Kim, D, Malhotra, H, Malhotra, P, Matsumura, I, Melo, J, Ohnishi, K, Ohno, R, Saikia, T, Schwarer, A, Takahashi, N, Tam, C, Tauchi, T, Usuki, K, Wang, J, Abdel-Rahman, F, Aljurf, M, Bazarba-Chi, A, Yehuda, D, Chaudhri, N, Durosinmi, M, Kamel, H, Louw, V, Matti, B, Nagler, A, Raanani, P, and Salem, Z
- Subjects
medicine.medical_specialty ,Drug Industry ,Cost effectiveness ,Cancer drugs ,Immunology ,Alternative medicine ,Antineoplastic Agents ,Pharmacology ,Biochemistry ,Drug Costs ,Antineoplastic Agent ,Patents as Topic ,Myelogenous ,hemic and lymphatic diseases ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Health care ,Medicine ,Drugs, Generic ,Humans ,Intensive care medicine ,health care economics and organizations ,Drug Cost ,business.industry ,Myeloid leukemia ,Hematology ,Cell Biology ,medicine.disease ,Leukemia ,business ,Large group ,Human - Abstract
As a group of more than 100 experts in chronic myeloid leukemia (CML), we draw attention to the high prices of cancer drugs, with the particular focus on the prices of approved tyrosine kinase inhibitors for the treatment of CML. This editorial addresses the multiple factors involved in cancer drug pricing and their impact on individual patients and health care policies, and argues for the need to (1) lower the prices of cancer drugs to allow more patients to afford them and (2) maintain sound long-term health care policies.
- Published
- 2013
36. Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial.
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Gambacorti-Passerini C, Brümmendorf TH, Abruzzese E, Kelly KR, Oehler VG, García-Gutiérrez V, Hjorth-Hansen H, Ernst T, Leip E, Purcell S, Luscan G, Viqueira A, Giles FJ, and Hochhaus A
- Abstract
This final analysis from the phase 4 BYOND trial reports outcomes with bosutinib in patients with previously treated chronic myeloid leukemia (CML); 163 patients with CML resistant/intolerant to previous tyrosine kinase inhibitors received bosutinib (starting dose: 500 mg QD). At study completion (median follow-up, 47.8 months), 48.1% (n = 75/156) of patients with Philadelphia chromosome-positive chronic phase CML were still receiving treatment. Among evaluable patients, 71.8% (95% CI, 63.9-78.9) and 59.7% (95% CI, 51.4-67.7) attained or maintained major molecular response (MMR) and molecular response (MR)
4 , respectively, at any time on treatment. The majority of patients achieved a deeper molecular response relative to baseline while on bosutinib. Kaplan-Meier probabilities (95% CI) of maintaining MMR and MR4 at 36 months were 87.2% (78.0-92.7) and 80.7% (69.4-88.1), respectively. At 48 months, the Kaplan-Meier overall survival rate was 88.3% (95% CI, 81.8-92.6); there were 17 deaths, including 2 that were considered CML related. Long-term adverse events (AEs) were consistent with the known safety profile of bosutinib, and no new safety issues were identified. The management of AEs through dose reduction maintained efficacy while improving tolerability. These results support the use of bosutinib in patients with previously treated CML.ClinicalTrials.gov, NCT02228382., (© 2024. The Author(s).)- Published
- 2024
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37. Health-related quality of life and symptoms of chronic myeloid leukemia patients after discontinuation of tyrosine kinase inhibitors: results from the EURO-SKI Trial.
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Efficace F, Mahon FX, Richter J, Piciocchi A, Cipriani M, Nicolini FE, Mayer J, Zackova D, Janssen JJWM, Panayiotidis P, Vestergaard H, Koskenvesa P, Almeida A, Hjorth-Hansen H, Martinez-Lopez J, Olsson-Strömberg U, Hochhaus A, Berger MG, Etienne G, Klamova H, Faber E, Rousselot P, Pfirrmann M, and Saussele S
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- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Young Adult, Europe, Fatigue chemically induced, Surveys and Questionnaires, Treatment Interruption, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Quality of Life, Tyrosine Kinase Inhibitors therapeutic use
- Abstract
Limited data is available on the health-related quality of life (HRQoL) and symptoms of patients with chronic myeloid leukemia (CML) who are in treatment-free remission (TFR). We herein report HRQoL results from the EURO-SKI trial. Patients who had been on tyrosine kinase inhibitors (TKIs) therapy for at least 3 years and achieved MR4 for at least 1 year were enrolled from 11 European countries, and the EORTC QLQ-C30 and the FACIT-Fatigue questionnaires were used to assess HRQoL and fatigue respectively. Patients were categorized into the following age groups: 18-39, 40-59, 60-69 and ≥70 years. Of 728 patients evaluated at baseline, 686 (94%) completed HRQoL assessments. The median age at TKI discontinuation was 60 years. Our findings indicate that HRQoL and symptom trajectories may vary depending on specific age groups, with younger patients benefiting the most. Improvements in patients aged 60 years or older were marginal across several HRQoL and symptom domains. At the time of considering TKI discontinuation, physicians could inform younger patients that they may expect valuable HRQoL benefits. Considering the marginal improvements observed in patients aged 60 years or above, it may be important to further investigate the value of TFR compared to a lowest effective dose approach in this older group of patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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38. European Stop Tyrosine Kinase Inhibitor Trial (EURO-SKI) in Chronic Myeloid Leukemia: Final Analysis and Novel Prognostic Factors for Treatment-Free Remission.
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Mahon FX, Pfirrmann M, Dulucq S, Hochhaus A, Panayiotidis P, Almeida A, Mayer J, Hjorth-Hansen H, Janssen JJWM, Mustjoki S, Martinez-Lopez J, Vestergaard H, Ehrencrona H, Machová Poláková K, Olsson-Strömberg U, Ossenkoppele G, Berger MG, Etienne G, Dengler J, Brümmendorf TH, Burchert A, Réa D, Rousselot P, Nicolini FE, Hofmann WK, Richter J, and Saussele S
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- Humans, Female, Middle Aged, Male, Adult, Aged, Prognosis, Imatinib Mesylate therapeutic use, Fusion Proteins, bcr-abl genetics, Fusion Proteins, bcr-abl antagonists & inhibitors, Pyrimidines therapeutic use, Europe, Young Adult, Aged, 80 and over, Treatment Outcome, Tyrosine Kinase Inhibitors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Protein Kinase Inhibitors therapeutic use, Remission Induction
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The European Stop Kinase Inhibitors (EURO-SKI) study is the largest clinical trial for investigating the cessation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in stable deep molecular remission (DMR). Among 728 patients, 434 patients (61%; 95% CI, 57 to 64) remained in major molecular response (MMR) at 6 months and 309 patients of 678 (46%; 95% CI, 42 to 49) at 36 months. Duration of TKI treatment and DMR before TKI stop were confirmed as significant factors for the prediction of MMR loss at 6 months. In addition, the type of BCR::ABL1 transcript was identified as a prognostic factor. For late MMR losses after 6 months, TKI treatment duration, percentage of blasts in peripheral blood, and platelet count at diagnosis were significant factors in multivariate analysis. For the entire study period of 36 months, multiple logistic regression models confirmed duration of treatment, blasts, and transcript type as independent factors for MMR maintenance. In addition to the duration of treatment, transcript type as well as blasts in peripheral blood at diagnosis should be considered as important factors to predict treatment-free remission.
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- 2024
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39. Correction: Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib - interim results from the DAstop2 trial.
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Flygt H, Söderlund S, Richter J, Saussele S, Koskenvesa P, Stenke L, Mustjoki S, Dimitrijevic A, Stentoft J, Majeed W, Roy L, Wolf D, Dreimane A, Gjertsen BT, Gedde-Dahl T, Ahlstrand E, Markevärn B, Hjorth-Hansen H, Janssen J, and Olsson-Strömberg U
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- 2024
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40. Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib - interim results from the DAstop2 trial.
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Flygt H, Söderlund S, Richter J, Saussele S, Koskenvesa P, Stenke L, Mustjoki S, Dimitrijevic A, Stentoft J, Majeed W, Roy L, Wolf D, Dreimane A, Gjertsen BT, Gedde-Dahl T, Ahlstrand E, Markevärn B, Hjorth-Hansen H, Janssen J, and Olsson-Strömberg U
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- Humans, Dasatinib adverse effects, Prospective Studies, Remission Induction, Treatment Outcome, Protein Kinase Inhibitors adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for ≥ one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for ≥1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2
nd stop. After a median follow-up of 27 months from 2nd stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop., (© 2024. The Author(s).)- Published
- 2024
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41. A patient with minimal myeloma treatment who survived for 20 years.
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Behsen AD, Vandsemb EN, Slørdahl TS, Hjorth-Hansen H, Quist-Paulsen P, Misund K, Sponaas AM, and Waage A
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- Humans, Multiple Myeloma drug therapy
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- 2024
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42. The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib.
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Machova Polakova K, Albeer A, Polivkova V, Krutska M, Vlcanova K, Curik N, Fabarius A, Klamova H, Spiess B, Waller CF, Brümmendorf TH, Dengler J, Kunzmann V, Burchert A, Belohlavkova P, Mustjoki S, Faber E, Mayer J, Zackova D, Panayiotidis P, Richter J, Hjorth-Hansen H, Kamińska M, Płonka M, Szczepanek E, Szarejko M, Bober G, Hus I, Grzybowska-Izydorczyk O, Wasilewska E, Paczkowska E, Niesiobędzka-Krężel J, Giannopoulos K, Mahon FX, Sacha T, Saußele S, and Pfirrmann M
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- Humans, Imatinib Mesylate therapeutic use, Prognosis, Protein Kinase Inhibitors therapeutic use, Membrane Transport Proteins therapeutic use, Treatment Outcome, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Antineoplastic Agents adverse effects
- Abstract
Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR., (© 2023. The Author(s).)
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- 2024
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43. Single-cell analysis of immune recognition in chronic myeloid leukemia patients following tyrosine kinase inhibitor discontinuation.
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Huuhtanen J, Adnan-Awad S, Theodoropoulos J, Forstén S, Warfvinge R, Dufva O, Bouhlal J, Dhapola P, Duàn H, Laajala E, Kasanen T, Klievink J, Ilander M, Jaatinen T, Olsson-Strömberg U, Hjorth-Hansen H, Burchert A, Karlsson G, Kreutzman A, Lähdesmäki H, and Mustjoki S
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- Humans, Hepatitis A Virus Cellular Receptor 2, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Single-Cell Analysis, Tyrosine Kinase Inhibitors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
- Abstract
Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML (n = 13, N = 25), other cancers (n = 28), and healthy (n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56
dim cluster with high expression of GZMA/B, PRF1, CCL3/4, and IFNG, with interactions with leukemic cells via inhibitory LGALS9-TIM3 and PVR-TIGIT interactions. Accordingly, upregulation of LGALS9 was observed in CML target cells and TIM3 in NK cells when co-cultured together. Additionally, we created a classifier to identify TCRs targeting leukemia-associated antigen PR1 and quantified anti-PR1 T cells in 90 CML and 786 healthy TCRβ-sequenced samples. Anti-PR1 T cells were more prevalent in CML, enriched in bone marrow samples, and enriched in the mature, cytotoxic CD8 + TEMRA cluster, especially in a patient maintaining TFR. Our results highlight the role of NK cells and anti-PR1 T cells in anti-leukemic immune responses in CML., (© 2023. The Author(s).)- Published
- 2024
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44. Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response: clinical and immunological effects.
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Geelen IGP, Gullaksen SE, Ilander MM, Olssen-Strömberg U, Mustjoki S, Richter J, Blijlevens NMA, Smit WM, Gjertsen BT, Gedde-Dahl T, Markevärn B, Koppes MMA, Westerweel PE, Hjorth-Hansen H, and Janssen JJWM
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- Humans, Fusion Proteins, bcr-abl genetics, Imatinib Mesylate therapeutic use, Interferon-alpha therapeutic use, Polyethylene Glycols therapeutic use, Pyrimidines therapeutic use, Treatment Outcome, Leukemia, Myeloid, Chronic-Phase drug therapy, Protein Kinase Inhibitors therapeutic use
- Abstract
In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1
IS (MR4.0 ) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0 . The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile. This trial was registered at www.clinicaltrials.gov as #NCT01866553., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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45. IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia.
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Huuhtanen J, Ilander M, Yadav B, Dufva OM, Lähteenmäki H, Kasanen T, Klievink J, Olsson-Strömberg U, Stentoft J, Richter J, Koskenvesa P, Höglund M, Söderlund S, Dreimane A, Porkka K, Gedde-Dahl T, Gjertsen BT, Stenke L, Myhr-Eriksson K, Markevärn B, Lübking A, Dimitrijevic A, Udby L, Bjerrum OW, Hjorth-Hansen H, and Mustjoki S
- Subjects
- CD8-Positive T-Lymphocytes, Cytokines metabolism, Dasatinib pharmacology, Dasatinib therapeutic use, Humans, Interferon-alpha, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism
- Abstract
In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-α is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-α in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCRβ sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8+ recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-α reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-α had costimulatory effects on TCR signaling. Our work supports the combination of IFN-α with TKI therapy, as IFN-α broadens the immune repertoire and restores immunological function.
- Published
- 2022
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46. Long-term tolerability and efficacy after initial PegIFN-α addition to dasatinib in CML-CP: Five-year follow-up of the NordCML007 study.
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Flygt H, Söderlund S, Stentoft J, Richter J, Koskenvesa P, Mustjoki S, Majeed W, Lübking A, Dreimane A, Markevärn B, Stenke L, Myhr Eriksson K, Gjertsen BT, Gedde-Dahl T, Dimitrijevic A, Udby L, Olsson-Strömberg U, and Hjorth-Hansen H
- Subjects
- Adult, Aged, Dasatinib administration & dosage, Female, Follow-Up Studies, Humans, Interferon-alpha administration & dosage, Male, Middle Aged, Polyethylene Glycols administration & dosage, Recombinant Proteins administration & dosage, Recombinant Proteins therapeutic use, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dasatinib therapeutic use, Interferon-alpha therapeutic use, Leukemia, Myeloid, Chronic-Phase drug therapy, Polyethylene Glycols therapeutic use
- Abstract
Objectives: Treatment-free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML-CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon-α in addition to TKI has shown promising efficacy but with dose-dependent toxicity and discontinuations. NordCML007 was initiated to study the efficacy and safety of low dose pegylated IFN-α (PegIFN-α) in combination with dasatinib (DAS) in CML-CP., Methods: Forty patients with newly diagnosed CML-CP were given DAS upfront. After month 3 (M3) 15 μg/wk of PegIFN-α was added and increased to 25 μg/wk from M7 until M15. DAS treatment was continued and adverse events and BCR-ABL1 qRT-PCR values were reported yearly after M24. Results from M1 to M18 have previously been published, and here we present long-term data., Results: After 5 years of follow-up, there were no suspected unexpected serious adverse reactions, no increase in serosal effusions, no disease progressions and no CML-related deaths. Rates of MR
3.0 (MMR), MR4.0 and MR4.5 were 84.6%, 64.1% and 51.3% respectively at M60, and 95% of patients reached MMR at some point during the study., Conclusion: Initial addition of PegIFN-α to DAS shows good long-term efficacy without increased toxicity., (© 2021 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)- Published
- 2021
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47. Molecular status 36 months after TKI discontinuation in CML is highly predictive for subsequent loss of MMR-final report from AFTER-SKI.
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Richter J, Lübking A, Söderlund S, Lotfi K, Markevärn B, Själander A, Stenke L, Deneberg S, Ahlstrand E, Myhr-Eriksson K, Panayiotidis P, Gedde-Dahl T, Žáčková D, Mayer J, Olsson-Strömberg U, Mahon FX, Saussele S, Hjorth-Hansen H, and Koskenvesa P
- Subjects
- Europe epidemiology, Fusion Proteins, bcr-abl genetics, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Neoplasm Recurrence, Local chemically induced, Neoplasm Recurrence, Local epidemiology, Prognosis, Remission Induction, Time Factors, Clinical Trials as Topic methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Neoplasm Recurrence, Local diagnosis, Protein Kinase Inhibitors adverse effects, Withholding Treatment statistics & numerical data
- Published
- 2021
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48. Cold agglutinin disease revisited: a multinational, observational study of 232 patients.
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Berentsen S, Barcellini W, D'Sa S, Randen U, Tvedt THA, Fattizzo B, Haukås E, Kell M, Brudevold R, Dahm AEA, Dalgaard J, Frøen H, Hallstensen RF, Jæger PH, Hjorth-Hansen H, Małecka A, Oksman M, Rolke J, Sekhar M, Sørbø JH, Tjønnfjord E, Tsykunova G, and Tjønnfjord GE
- Subjects
- Adult, Aged, Anemia, Hemolytic, Autoimmune etiology, Anemia, Hemolytic, Autoimmune immunology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Retrospective Studies, Vidarabine administration & dosage, Anemia, Hemolytic, Autoimmune drug therapy, Bendamustine Hydrochloride administration & dosage, Rituximab administration & dosage, Vidarabine analogs & derivatives
- Abstract
We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in 5 countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate fourfold differences between cold and warmer climates regarding prevalence (20 vs 5 cases/million) and incidence (1.9 vs 0.48 cases/million per year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin <8 g/dL. Identification of typical features of CAD-associated lymphoproliferative disorder in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work includes a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift toward deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects., (© 2020 by The American Society of Hematology.)
- Published
- 2020
- Full Text
- View/download PDF
49. Plasma proteomics of biomarkers for inflammation or cancer cannot predict relapse in chronic myeloid leukaemia patients stopping tyrosine kinase inhibitor therapy.
- Author
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Söderlund S, Persson I, Ilander M, Guilhot J, Hjorth-Hansen H, Koskenvesa P, Richter J, Saussele S, Mustjoki S, and Olsson-Strömberg U
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Middle Aged, Molecular Targeted Therapy, Prognosis, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Recurrence, Treatment Outcome, Young Adult, Biomarkers, Blood Proteins, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Proteome, Proteomics methods
- Abstract
Several studies have now shown that chronic myeloid leukaemia (CML) patients in deep molecular remission may discontinue tyrosine kinase inhibitor (TKI) treatment with a treatment free remission (TFR) rate of approximately 40-60 %. Some factors influencing the possibility of TFR have been described but better tools are needed for individual prediction of long-term TFR. Herein, two multiplex panels were utilised to analyse a total of 162 different plasma proteins from 56 patients included in the TKI stopping trial EURO-SKI (Saussele et al., 2018). The purpose was to identify possible plasma protein markers for prediction of successful TKI discontinuation and to evaluate effects of TKI discontinuation on plasma protein profiles. No protein biomarkers sampled before TKI discontinuation could separate relapse cases from non-relapse cases but some plasma proteins differed between patients who relapsed and those who remained in TFR when followed over time after TKI cessation. In conclusion, the plasma protein markers in this study could not predict relapse after TKI discontinuation but may be of use to understand the mechanisms involved in maintenance of TFR., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
50. The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.
- Author
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Rio-Machin A, Vulliamy T, Hug N, Walne A, Tawana K, Cardoso S, Ellison A, Pontikos N, Wang J, Tummala H, Al Seraihi AFH, Alnajar J, Bewicke-Copley F, Armes H, Barnett M, Bloor A, Bödör C, Bowen D, Fenaux P, Green A, Hallahan A, Hjorth-Hansen H, Hossain U, Killick S, Lawson S, Layton M, Male AM, Marsh J, Mehta P, Mous R, Nomdedéu JF, Owen C, Pavlu J, Payne EM, Protheroe RE, Preudhomme C, Pujol-Moix N, Renneville A, Russell N, Saggar A, Sciuccati G, Taussig D, Toze CL, Uyttebroeck A, Vandenberghe P, Schlegelberger B, Ripperger T, Steinemann D, Wu J, Mason J, Page P, Akiki S, Reay K, Cavenagh JD, Plagnol V, Caceres JF, Fitzgibbon J, and Dokal I
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adenosine Deaminase genetics, Axonemal Dyneins genetics, Cohort Studies, Humans, Nonsense Mediated mRNA Decay, Pedigree, Perforin genetics, Platelet Membrane Glycoproteins genetics, RNA Helicases genetics, Receptors, Interleukin-17 genetics, Vesicular Transport Proteins genetics, Exome Sequencing, Germ-Line Mutation, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes genetics
- Abstract
The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management.
- Published
- 2020
- Full Text
- View/download PDF
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