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163 results on '"Hjorth-Hansen, H"'

1. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Author

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., and Hehlmann, R.

Published
2020
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5. P950: COMBINED PROTEASOME AND AUTOPHAGY INHIBITION IN RELAPSED/REFRACTORY MULTIPLE MYELOMA – A PHASE I TRIAL OF HYDROXYCHLOROQUINE, CARFILZOMIB AND DEXAMETHASONE

Author

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. Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study

Author

Hochhaus, A, Gambacorti Passerini, C, Abboud, C, Gjertsen, B, Brummendorf, T, Smith, B, Ernst, T, Giraldo-Castellano, P, Olsson-Stromberg, U, Saussele, S, Bardy-Bouxin, N, Viqueira, A, Leip, E, Russell-Smith, T, Leone, J, Rosti, G, Watts, J, Giles, F, Abruzzese, E, Akard, L, Bosi, A, Cervantes, F, Charbonnier, A, Di Raimondo, F, Etienne, G, Garcia Gutierrez, V, Guerci-Bresler, A, Hjorth-Hansen, H, Karsenti, J, Kelly, K, Le Coutre, P, Martinez Chamorro, C, Oehler, V, Orti Pascual, G, Petzer, A, Pungolino, E, Rege-Cambrin, G, Rigal-Huguet, F, Roboz, G, Rousselot, P, Sanchez-Guijo, F, Sanz Santillana, G, Schafhausen, P, Scheid, C, Schmidt, S, Specchia, G, Steegmann, J, Stenke, L, Hochhaus A., Gambacorti Passerini C., Abboud C., Gjertsen B. T., Brummendorf T. H., Smith B. D., Ernst T., Giraldo-Castellano P., Olsson-Stromberg U., Saussele S., Bardy-Bouxin N., Viqueira A., Leip E., Russell-Smith T. A., Leone J., Rosti G., Watts J., Giles F. J., Abruzzese E., Akard L. P., Bosi A., Cervantes F., Charbonnier A., Di Raimondo F., Etienne G., Garcia Gutierrez V., Guerci-Bresler A. P., Hjorth-Hansen H., Karsenti J. M., Kelly K. R., Le Coutre P., Martinez Chamorro C., Oehler V. G., Orti Pascual G., Petzer A., Pungolino E., Rege-Cambrin G., Rigal-Huguet F., Roboz G. J., Rousselot P., Sanchez-Guijo F. M., Sanz Santillana G., Schafhausen P., Scheid C., Schmidt S., Specchia G., Steegmann J. L., Stenke L., Hochhaus, A, Gambacorti Passerini, C, Abboud, C, Gjertsen, B, Brummendorf, T, Smith, B, Ernst, T, Giraldo-Castellano, P, Olsson-Stromberg, U, Saussele, S, Bardy-Bouxin, N, Viqueira, A, Leip, E, Russell-Smith, T, Leone, J, Rosti, G, Watts, J, Giles, F, Abruzzese, E, Akard, L, Bosi, A, Cervantes, F, Charbonnier, A, Di Raimondo, F, Etienne, G, Garcia Gutierrez, V, Guerci-Bresler, A, Hjorth-Hansen, H, Karsenti, J, Kelly, K, Le Coutre, P, Martinez Chamorro, C, Oehler, V, Orti Pascual, G, Petzer, A, Pungolino, E, Rege-Cambrin, G, Rigal-Huguet, F, Roboz, G, Rousselot, P, Sanchez-Guijo, F, Sanz Santillana, G, Schafhausen, P, Scheid, C, Schmidt, S, Specchia, G, Steegmann, J, Stenke, L, Hochhaus A., Gambacorti Passerini C., Abboud C., Gjertsen B. T., Brummendorf T. H., Smith B. D., Ernst T., Giraldo-Castellano P., Olsson-Stromberg U., Saussele S., Bardy-Bouxin N., Viqueira A., Leip E., Russell-Smith T. A., Leone J., Rosti G., Watts J., Giles F. J., Abruzzese E., Akard L. P., Bosi A., Cervantes F., Charbonnier A., Di Raimondo F., Etienne G., Garcia Gutierrez V., Guerci-Bresler A. P., Hjorth-Hansen H., Karsenti J. M., Kelly K. R., Le Coutre P., Martinez Chamorro C., Oehler V. G., Orti Pascual G., Petzer A., Pungolino E., Rege-Cambrin G., Rigal-Huguet F., Roboz G. J., Rousselot P., Sanchez-Guijo F. M., Sanz Santillana G., Schafhausen P., Scheid C., Schmidt S., Specchia G., Steegmann J. L., and Stenke L.

Abstract

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.

Published
2020

13. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial

Author

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

14. 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

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
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16. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia

Author

Ilander, M, Olsson-Strömberg, U, Schlums, H, Guilhot, J, Brück, O, Lähteenmäki, H, Kasanen, T, Koskenvesa, P, Söderlund, S, Höglund, M, Markevärn, B, Själander, Anders, 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, Mustjoki, S, Ilander, M, Olsson-Strömberg, U, Schlums, H, Guilhot, J, Brück, O, Lähteenmäki, H, Kasanen, T, Koskenvesa, P, Söderlund, S, Höglund, M, Markevärn, B, Själander, Anders, 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 CD56(bright) NK 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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17. CHRONIC MYELOID LEUKEMIA PATIENTS WERE NOT DIFFERENT IN MOLECULAR RELAPSE AFTER STOPPING IMATINIB IN MR4 WHETHER RESIDUAL DISEASE WAS DETECTED OR NOT - WHEN ADJUSTING FOR NUMBER OF CONTROL TRANSCRIPTS

Author

Pfirrmann, M., Mahon, F-X, Guilhot, J., Richter, J., Almeida, A., Janssen, J. J., Mayer, J., Koskenvesa, P., Panayiotidis, P., Strömberg, Ulla Ohlsson, Berger, M. G., Diamond, J., Ehrencrona, H., Kairisto, V., Polakova, K. Machova, Mueller, M. C., Mustjoki, S., Hochhaus, A., Saussele, S., Hjorth-Hansen, H., Pfirrmann, M., Mahon, F-X, Guilhot, J., Richter, J., Almeida, A., Janssen, J. J., Mayer, J., Koskenvesa, P., Panayiotidis, P., Strömberg, Ulla Ohlsson, Berger, M. G., Diamond, J., Ehrencrona, H., Kairisto, V., Polakova, K. Machova, Mueller, M. C., Mustjoki, S., Hochhaus, A., Saussele, S., and Hjorth-Hansen, H.

Published
2017

18. CLINICAL AND IMMUNOLOGICAL EFFECTS OF NILOTINIB IN COMBINATION WITH PEGYLATED INTERFERON-A2B IN PATIENTS WITH SUBOPTIMAL MOLECULAR RESPONSE ON IMATINIB (NORDDUTCHCML009)

Author

Geelen, I., Strömberg, Ulla Ohlsson, Mustjoki, S., Richter, J., Blijlevens, N., Smit, W., Gjertsen, B., Gedde-Dahl, T., Markevärn, B., Koppes, M., Westerweel, P., Janssen, J., Hjorth-Hansen, H., Geelen, I., Strömberg, Ulla Ohlsson, Mustjoki, S., Richter, J., Blijlevens, N., Smit, W., Gjertsen, B., Gedde-Dahl, T., Markevärn, B., Koppes, M., Westerweel, P., Janssen, J., and Hjorth-Hansen, H.

Published
2017

19. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia

Author

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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20. Plasma Proteomics In Chronic Myeloid Leukemia Patients Before And After Initiation Of Tyrosine Kinase Inhibitor Therapy Reveals Induced Th1 Immunity And Loss Of Angiogenic Stimuli

Author

Söderlund, Stina, Christiansson, Lisa, Persson, Inger, Hjorth-Hansen, H., Richter, J., Simonsson, Bengt, Mustjoki, S., Olsson-Strömberg, Ulla, Loskog, Angelica, Söderlund, Stina, Christiansson, Lisa, Persson, Inger, Hjorth-Hansen, H., Richter, J., Simonsson, Bengt, Mustjoki, S., Olsson-Strömberg, Ulla, and Loskog, Angelica

Published
2016

21. Safety and efficacy of the combination of pegylated interferon-alpha 2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients

Author

Hjorth-Hansen, H., Stentoft, J., Richter, J., Koskenvesa, P., Höglund, Martin, Dreimane, A., Porkka, K., Gedde-Dahl, T., Gjertsen, B. T., Gruber, F. X., Stenke, L., Eriksson, K. M., Markevarn, B., Lubking, A., Vestergaard, H., Udby, L., Bjerrum, O. W., Persson, Inger, Mustjoki, S., Olsson-Strömberg, Ulla, Hjorth-Hansen, H., Stentoft, J., Richter, J., Koskenvesa, P., Höglund, Martin, Dreimane, A., Porkka, K., Gedde-Dahl, T., Gjertsen, B. T., Gruber, F. X., Stenke, L., Eriksson, K. M., Markevarn, B., Lubking, A., Vestergaard, H., Udby, L., Bjerrum, O. W., Persson, Inger, Mustjoki, S., and Olsson-Strömberg, Ulla

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-alpha 2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 mu g/week and it increased to 25 mu g/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, MR4 was achieved by 46% and MR4.5 by 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.

Published
2016
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22. Stopping Tyrosine Kinase Inhibitors In A Very Large Cohort Of European Chronic Myeloid Leukemia Patients : Results Of The Euro-Ski Trial

Author

Richter, J., Mahon, F. X., Guilhot, J., Hjorth-Hansen, H., Almeida, A., Janssen, J. J., Mayer, J., Porkka, K., Panayiotidis, P., Olsson-Strömberg, Ulla, Berger, M. G., Diamond, J., Ehrencrona, H., Kairisto, V., Polakova, K. Machova, Muller, M. C., Mustjoki, S., Hochhaus, A., Pfirrmann, M., Saussele, S., Richter, J., Mahon, F. X., Guilhot, J., Hjorth-Hansen, H., Almeida, A., Janssen, J. J., Mayer, J., Porkka, K., Panayiotidis, P., Olsson-Strömberg, Ulla, Berger, M. G., Diamond, J., Ehrencrona, H., Kairisto, V., Polakova, K. Machova, Muller, M. C., Mustjoki, S., Hochhaus, A., Pfirrmann, M., and Saussele, S.

Published
2016

24. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

Author

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

27. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment ofhigh-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNetStudy

Author

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

28. 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

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

29. Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients

Author

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., Markevarn, B., Olofsson, T., Olsson-Stromberg, U., Rapakko, K., Thunberg, Sarah, Stenke, L., Simonsson, B., Porkka, K., Hjorth-Hansen, H., Grp, Nordic CML Study, 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., Markevarn, B., Olofsson, T., Olsson-Stromberg, U., Rapakko, K., Thunberg, Sarah, Stenke, L., Simonsson, B., Porkka, K., Hjorth-Hansen, H., and Grp, Nordic CML Study

Abstract

Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38=) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P = 0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P = 0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients., QC 20170419

Published
2013
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30. 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

Author

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, Salem, Z, Abboud, Camille, Berman, Ellin, Cohen, Adam, Cortes, Jorge, DeAngelo, Daniel, Deininger, Michael, Devine, Steven, Druker, Brian, Fathi, Amir, Jabbour, Elias, Jagasia, Madan, Kantarjian, Hagop, Khoury, Jean, Laneuville, Pierre, Larson, Richard, Lipton, Jeffrey, Moore, Joseph O., Mughal, Tariq, O'Brien, Susan, Pinilla-Ibarz, Javier, Quintas-Cardama, Alfonso, Radich, Jerald, Reddy, Vishnu, Schiffer, Charles, Shah, Neil, Shami, Paul, Silver, Richard T., Snyder, David, Stone, Richard, Talpaz, Moshe, Tefferi, Ayalew, Van Etten, Richard A., Wetzler, Meir, Abruzzese, Elisabetta, Apperley, Jane, Breccia, Massimo, Byrne, Jenny, Cervantes, Francisco, Chelysheva, Ekaterina, Clark, R. E., De Lavallade, Hugues, Dyagil, Iryna, Gambacorti-Passerini, Carlo, Goldman, John, Haznedaroglu, Ibrahim, Hjorth-Hansen, Henrik, Holyoake, Tessa, Huntly, Brian, Le Coutre, Philipp, Lomaia, Elza, Mahon, Francois-Xavier, Marin-Costa, David, Martinelli, Giovanni, Mayer, Jiri, Milojkovic, Dragana, Olavarria, Eduardo, Porkka, Kimmo, Richter, Johan, Rousselot, Philippe, Saglio, Giuseppe, Saydam, Guray, Stentoft, Jesper, Turkina, Anna, Vigneri, Paolo, Zaritskey, Andrey, Aguayo, Alvaro, Ayala, Manuel, Bendit, Israel, Bengio, Raquel Maria, Best, Carlos, Bullorsky, Eduardo, Cervera, Eduardo, Desouza, Carmino, Fanilla, Ernesto, Gomez-Almaguer, David, Hamerschlak, Nelson, Lopez, Jose, Magarinos, Alicia, Meillon, Luis, Milone, Jorge, Moiraghi, Beatriz, Pasquini, Ricardo, Pavlovsky, Carolina, Ruiz-Arguelles, Guillermo J., Spector, Nelson, Arthur, Christopher, Browett, Peter, Grigg, Andrew, Hu, Jianda, Huang, Xiao-jun, Hughes, Tim, Jiang, Qian, Jootar, Saengsuree, Kim, Dong-Wook, Malhotra, Hemant, Malhotra, Pankaj, Matsumura, Itaru, Melo, Junia, Ohnishi, Kazunori, Ohno, Ryuzo, Saikia, Tapan, Schwarer, Anthony P., Takahashi, Naoto, Tam, Constantine, Tauchi, Tetsuzo, Usuki, Kensuke, Wang, Jianxiang, Abdel-Rahman, Fawzi, Aljurf, Mahmoud Deeb Saeed, Bazarba-Chi, Ali, Yehuda, Dina Ben, Chaudhri, Naeem, Durosinmi, Muheez, Kamel, Hossam, Louw, Vernon, Matti, Bassam Francis, Nagler, Arnon, Raanani, Pia, Salem, Ziad, 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, Salem, Z, Abboud, Camille, Berman, Ellin, Cohen, Adam, Cortes, Jorge, DeAngelo, Daniel, Deininger, Michael, Devine, Steven, Druker, Brian, Fathi, Amir, Jabbour, Elias, Jagasia, Madan, Kantarjian, Hagop, Khoury, Jean, Laneuville, Pierre, Larson, Richard, Lipton, Jeffrey, Moore, Joseph O., Mughal, Tariq, O'Brien, Susan, Pinilla-Ibarz, Javier, Quintas-Cardama, Alfonso, Radich, Jerald, Reddy, Vishnu, Schiffer, Charles, Shah, Neil, Shami, Paul, Silver, Richard T., Snyder, David, Stone, Richard, Talpaz, Moshe, Tefferi, Ayalew, Van Etten, Richard A., Wetzler, Meir, Abruzzese, Elisabetta, Apperley, Jane, Breccia, Massimo, Byrne, Jenny, Cervantes, Francisco, Chelysheva, Ekaterina, Clark, R. E., De Lavallade, Hugues, Dyagil, Iryna, Gambacorti-Passerini, Carlo, Goldman, John, Haznedaroglu, Ibrahim, Hjorth-Hansen, Henrik, Holyoake, Tessa, Huntly, Brian, Le Coutre, Philipp, Lomaia, Elza, Mahon, Francois-Xavier, Marin-Costa, David, Martinelli, Giovanni, Mayer, Jiri, Milojkovic, Dragana, Olavarria, Eduardo, Porkka, Kimmo, Richter, Johan, Rousselot, Philippe, Saglio, Giuseppe, Saydam, Guray, Stentoft, Jesper, Turkina, Anna, Vigneri, Paolo, Zaritskey, Andrey, Aguayo, Alvaro, Ayala, Manuel, Bendit, Israel, Bengio, Raquel Maria, Best, Carlos, Bullorsky, Eduardo, Cervera, Eduardo, Desouza, Carmino, Fanilla, Ernesto, Gomez-Almaguer, David, Hamerschlak, Nelson, Lopez, Jose, Magarinos, Alicia, Meillon, Luis, Milone, Jorge, Moiraghi, Beatriz, Pasquini, Ricardo, Pavlovsky, Carolina, Ruiz-Arguelles, Guillermo J., Spector, Nelson, Arthur, Christopher, Browett, Peter, Grigg, Andrew, Hu, Jianda, Huang, Xiao-jun, Hughes, Tim, Jiang, Qian, Jootar, Saengsuree, Kim, Dong-Wook, Malhotra, Hemant, Malhotra, Pankaj, Matsumura, Itaru, Melo, Junia, Ohnishi, Kazunori, Ohno, Ryuzo, Saikia, Tapan, Schwarer, Anthony P., Takahashi, Naoto, Tam, Constantine, Tauchi, Tetsuzo, Usuki, Kensuke, Wang, Jianxiang, Abdel-Rahman, Fawzi, Aljurf, Mahmoud Deeb Saeed, Bazarba-Chi, Ali, Yehuda, Dina Ben, Chaudhri, Naeem, Durosinmi, Muheez, Kamel, Hossam, Louw, Vernon, Matti, Bassam Francis, Nagler, Arnon, Raanani, Pia, and Salem, Ziad

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

31. MAJOR MOLECULAR RESPONSE RATE AT ONE YEAR IS HIGHER IF PEGYLATED INTERFERON ALPHA-2B IS ADDED TO IMATINIB IN NON-HR CHRONIC MYELOID LEUKEMIA PATIENTS IN IMATINIB INDUCED COMPLETE HEMATOLOGICAL REMISSION in HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, vol 95, issue , pp 457-457

Author

Simonsson, B, Gedde-Dahl, M, Markevarn, M, Remes, P, Stentoft, R, Almqvist, S, Bjoreman, T, Flogegard, V, Hallman, U, Koskenveesa, L, Lindblom, A, Malm, Claes, Mustjoki, S, Myhr-Eriksson, K, Rasanen, A, Sinisalo, M, Sippola, R, Sjalander, A, Stromberg, U, Weiss Bjerrum, O, Ehrencrona, H, Gruber, F, Kairisto, V, Sandin, F, Nagler, A, Lanng Nielsen, J, Hjorth-Hansen, H, Porkka, K, Simonsson, B, Gedde-Dahl, M, Markevarn, M, Remes, P, Stentoft, R, Almqvist, S, Bjoreman, T, Flogegard, V, Hallman, U, Koskenveesa, L, Lindblom, A, Malm, Claes, Mustjoki, S, Myhr-Eriksson, K, Rasanen, A, Sinisalo, M, Sippola, R, Sjalander, A, Stromberg, U, Weiss Bjerrum, O, Ehrencrona, H, Gruber, F, Kairisto, V, Sandin, F, Nagler, A, Lanng Nielsen, J, Hjorth-Hansen, H, and Porkka, K

Abstract

n/a

Published
2010

32. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy

Author

Mustjoki, S., Ekblom, M., Arstila, T. P., Dybedal, I., Epling-Burnette, P. K., Guilhot, F., Hjorth-Hansen, H., Höglund, Martin, Kovanen, P., Laurinolli, T., Liesveld, J., Paquette, R., Pinilla-Ibarz, J., Rauhala, A., Shah, N., Simonsson, Bengt, Sinisalo, M., Steegmann, J. L., Stenke, L., Porkka, K., Mustjoki, S., Ekblom, M., Arstila, T. P., Dybedal, I., Epling-Burnette, P. K., Guilhot, F., Hjorth-Hansen, H., Höglund, Martin, Kovanen, P., Laurinolli, T., Liesveld, J., Paquette, R., Pinilla-Ibarz, J., Rauhala, A., Shah, N., Simonsson, Bengt, Sinisalo, M., Steegmann, J. L., Stenke, L., and Porkka, K.

Abstract

Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile.

Published
2009
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33. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system philadelphia chromosome positive leukemia

Author

Porkka, K. (Kimmo), Koskenvesa, P. (Perttu), Lundan, T. (Tuija), Rimpiläinen, J. (Johanna), Mustjoki, S. (Satu), Smykla, R. (Richard), Wild, R. (Robert), Luo, R. (Roger), Arnan, M. (Montserrat), Brethon, B. (Benoit), Eccersley, L. (Lydia), Hjorth-Hansen, H. (Henrik), Höglund, M. (Martin), Klamova, H. (Hana), Knutsen, H. (Håvar), Parikh, S. (Suhag), Raffoux, E. (Emmanuel), Gruber, F. (Franz), Brito-Babapulle, F. (Finella), Dombret, H. (Hervé), Duarte, R.F. (Rafael), Elonen, E. (Erkki), Paquette, R. (Ron), Zwaan, C.M. (Michel), Lee, F.Y.F. (Francis), Porkka, K. (Kimmo), Koskenvesa, P. (Perttu), Lundan, T. (Tuija), Rimpiläinen, J. (Johanna), Mustjoki, S. (Satu), Smykla, R. (Richard), Wild, R. (Robert), Luo, R. (Roger), Arnan, M. (Montserrat), Brethon, B. (Benoit), Eccersley, L. (Lydia), Hjorth-Hansen, H. (Henrik), Höglund, M. (Martin), Klamova, H. (Hana), Knutsen, H. (Håvar), Parikh, S. (Suhag), Raffoux, E. (Emmanuel), Gruber, F. (Franz), Brito-Babapulle, F. (Finella), Dombret, H. (Hervé), Duarte, R.F. (Rafael), Elonen, E. (Erkki), Paquette, R. (Ron), Zwaan, C.M. (Michel), and Lee, F.Y.F. (Francis)

Abstract

Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph+) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasatinib (a dual-specific SRC/BCR-ABL kinase inhibitor) were compared in a pre-clinical mouse model of intracranial Ph+ leukemia. Clinical dasatinib treatment in patients with CNS Ph+ leukemia was assessed. In preclinical studies, dasatinib increased survival, whereas imatinib failed to inhibit intracranial tumor growth. Stabilization and regression of CNS disease were achieved with continued dasatinib administration. The drug also demonstrated substantial activity in 11 adult and pediatric patients with CNS Ph+ leukemia. Eleven evaluable patients had clinically significant, long-lasting responses, which were complete in 7 patients. In 3 additional patients, isolated CNS relapse occurred during dasatinib therapy; and in 2 of them, it was caused by expansion of a BCR-ABL-mutated dasatinib-resistant clone, implying selection pressure exerted by the compound in the CNS. Dasatinib has promising therapeutic potential in managing intracranial leukemic disease and substantial clinical activity in patients who experience CNS relapse while on imatinib therapy. This study is registered at ClinicalTrials. gov as CA180006 (#NCT00108719) and CA180015 (#NCT00110097).

Published
2008
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34. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia

Author

Porkka, K, Koskenvesa, P, Lundan, T, Rimpilainen, J, Mustjoki, S, Smykla, R, Wild, R, Luo, R, Arnan, M, Brethon, B, Eccersley, L, Hjorth-Hansen, H, Hoglund, M, Klamova, H, Knutsen, H, Parikh, S, Raffoux, E, Gruber, F, Brito-Babapulle, F, Dombret, H, Duarte, RF, Elonen, E, Paquette, R, Zwaan, C.M., Lee, FYF, Porkka, K, Koskenvesa, P, Lundan, T, Rimpilainen, J, Mustjoki, S, Smykla, R, Wild, R, Luo, R, Arnan, M, Brethon, B, Eccersley, L, Hjorth-Hansen, H, Hoglund, M, Klamova, H, Knutsen, H, Parikh, S, Raffoux, E, Gruber, F, Brito-Babapulle, F, Dombret, H, Duarte, RF, Elonen, E, Paquette, R, Zwaan, C.M., and Lee, FYF

Published
2008

36. Safety and efficacy of the combination of pegylated interferon-a2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients

Author

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.

Published
2016
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38. Role of hepatocyte growth factor and its receptor c-met in multiple myeloma.

Author

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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43. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Author

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.

Subjects
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/.

Published
2020

44. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013

Author

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

Subjects
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.

Published
2013

45. 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

Author

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.

Subjects
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.

Published
2009

46. Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders

Author

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

Subjects
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.).

Published
2017

48. 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

Author

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

49. Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial.

Author

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

Subjects
Humans, Middle Aged, Female, Male, Aged, Adult, Aged, 80 and over, Treatment Outcome, Young Adult, Follow-Up Studies, Drug Resistance, Neoplasm drug effects, Aniline Compounds therapeutic use, Aniline Compounds adverse effects, Aniline Compounds administration & dosage, Nitriles adverse effects, Nitriles therapeutic use, Nitriles administration & dosage, Quinolines therapeutic use, Quinolines adverse effects, Quinolines administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors adverse effects
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 MR 4 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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50. Health-related quality of life and symptoms of chronic myeloid leukemia patients after discontinuation of tyrosine kinase inhibitors: results from the EURO-SKI Trial.

Author

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

Subjects
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.)

Published
2024
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