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1. The OCT2/MATE1 Interaction Between Trifluridine, Metformin and Cimetidine: A Crossover Pharmacokinetic Study

Author

Guchelaar, Niels A. D., Buck, Stefan A. J., van Doorn, Leni, Hussaarts, Koen G. A. M., Sandberg, Yorick, van der Padt-Pruijsten, Annemieke, van Alphen, Robbert J., Poppe-Manenschijn, Laura, Vleut, Isolde, de Bruijn, Peter, van Leeuwen, Roelof W. F., Mostert, Bianca, Eskens, Ferry A. L. M., Oomen-de Hoop, Esther, Koolen, Stijn L. W., and Mathijssen, Ron H. J.

Published
2024
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2. A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

Author

de Jonge, A. Vera, van Werkhoven, Erik, Dinmohamed, Avinash G., Nijland, Marcel, Zwinderman, Aeilko H., Bossuyt, Patrick M., Veldhuis, Martine S., Rutten, Emma G. G. M., Mous, Rogier, Vermaat, Joost S. P., Sandberg, Yorick, de Jongh, Eva, Bilgin, Yavuz M., Boersma, Rinske, Koene, Harry, Kersten, Marie José, de Jong, Daphne, and Chamuleau, Martine E. D.

Published
2023
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4. The OCT2/MATE1 Interaction Between Trifluridine, Metformin and Cimetidine:A Crossover Pharmacokinetic Study

Author

Guchelaar, Niels A. D., Buck, Stefan A. J., van Doorn, Leni, Hussaarts, Koen G. A. M., Sandberg, Yorick, van der Padt-pruijsten, Annemieke, van Alphen, Robbert J., Poppe-Manenschijn, Laura, Vleut, Isolde, de Bruijn, Peter, van Leeuwen, Roelof W. F., Mostert, Bianca, Eskens, Ferry A. L. M., Oomen-de Hoop, Esther, Koolen, Stijn L. W., Mathijssen, Ron H. J., Guchelaar, Niels A. D., Buck, Stefan A. J., van Doorn, Leni, Hussaarts, Koen G. A. M., Sandberg, Yorick, van der Padt-pruijsten, Annemieke, van Alphen, Robbert J., Poppe-Manenschijn, Laura, Vleut, Isolde, de Bruijn, Peter, van Leeuwen, Roelof W. F., Mostert, Bianca, Eskens, Ferry A. L. M., Oomen-de Hoop, Esther, Koolen, Stijn L. W., and Mathijssen, Ron H. J.

Abstract

Background and Objectives: Trifluridine/tipiracil, registered for the treatment of patients with metastatic gastric and colorectal cancer, is a substrate and inhibitor for the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion protein 1 (MATE1), which raises the potential for drug–drug interactions with other OCT2/MATE1 modulators. Therefore, we prospectively examined the effect of an OCT2/MATE1 inhibitor (cimetidine) and substrate (metformin) on the pharmacokinetics of trifluridine. Methods: In this three-phase crossover study, patients with metastatic colorectal or gastric cancer were sequentially treated with trifluridine/tipiracil alone (phase A), trifluridine/tipiracil concomitant with metformin (phase B) and trifluridine/tipiracil concomitant with cimetidine (phase C). The primary endpoint was the relative difference in exposure of trifluridine assessed by the area under the curve from timepoint zero to infinity. A > 30% change in exposure was considered clinically relevant. A p-value of < 0.025 was considered significant because of a Bonferroni correction. Results: Eighteen patients were included in the analysis. Metformin did not significantly alter the exposure to trifluridine (− 12.6%; 97.5% confidence interval − 25.0, 1.8; p = 0.045). Cimetidine did alter the exposure to trifluridine significantly (+ 18.0%; 97.5% confidence interval 4.5, 33.3; p = 0.004), but this increase did not meet our threshold for clinical relevance. Metformin trough concentrations were not influenced by trifluridine/tipiracil. Conclusions: Our result suggests that the OCT2/MATE1 modulators cimetidine and metformin can be co-administered with trifluridine/tipiracil without clinically relevant effects on drug exposure. Clinical Trial Registration: NL8067 (registered 04-10-2019).

Published
2024

9. Figure S2B from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

Xochelli, Aliki, primary, Baliakas, Panagiotis, primary, Kavakiotis, Ioannis, primary, Agathangelidis, Andreas, primary, Sutton, Lesley-Ann, primary, Minga, Eva, primary, Ntoufa, Stavroula, primary, Tausch, Eugen, primary, Yan, Xiao-Jie, primary, Shanafelt, Tait, primary, Plevova, Karla, primary, Boudjogra, Myriam, primary, Rossi, Davide, primary, Davis, Zadie, primary, Navarro, Alba, primary, Sandberg, Yorick, primary, Vojdeman, Fie Juhl, primary, Scarfo, Lydia, primary, Stavroyianni, Niki, primary, Sudarikov, Andrey, primary, Veronese, Silvio, primary, Tzenou, Tatiana, primary, Karan-Djurasevic, Teodora, primary, Catherwood, Mark, primary, Kienle, Dirk, primary, Chatzouli, Maria, primary, Facco, Monica, primary, Bahlo, Jasmin, primary, Pott, Christiane, primary, Pedersen, Lone Bredo, primary, Mansouri, Larry, primary, Smedby, Karin E., primary, Chu, Charles C., primary, Giudicelli, Véronique, primary, Lefranc, Marie-Paule, primary, Panagiotidis, Panagiotis, primary, Juliusson, Gunnar, primary, Anagnostopoulos, Achilles, primary, Vlahavas, Ioannis, primary, Antic, Darko, primary, Trentin, Livio, primary, Montillo, Marco, primary, Niemann, Carsten, primary, Döhner, Hartmut, primary, Langerak, Anton W., primary, Pospisilova, Sarka, primary, Hallek, Michael, primary, Campo, Elias, primary, Chiorazzi, Nicholas, primary, Maglaveras, Nikos, primary, Oscier, David, primary, Gaidano, Gianluca, primary, Jelinek, Diane F., primary, Stilgenbauer, Stephan, primary, Chouvarda, Ioanna, primary, Darzentas, Nikos, primary, Belessi, Chrysoula, primary, Davi, Frederic, primary, Hadzidimitriou, Anastasia, primary, Rosenquist, Richard, primary, Ghia, Paolo, primary, and Stamatopoulos, Kostas, primary

Published
2023
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10. Table S1 from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

Xochelli, Aliki, primary, Baliakas, Panagiotis, primary, Kavakiotis, Ioannis, primary, Agathangelidis, Andreas, primary, Sutton, Lesley-Ann, primary, Minga, Eva, primary, Ntoufa, Stavroula, primary, Tausch, Eugen, primary, Yan, Xiao-Jie, primary, Shanafelt, Tait, primary, Plevova, Karla, primary, Boudjogra, Myriam, primary, Rossi, Davide, primary, Davis, Zadie, primary, Navarro, Alba, primary, Sandberg, Yorick, primary, Vojdeman, Fie Juhl, primary, Scarfo, Lydia, primary, Stavroyianni, Niki, primary, Sudarikov, Andrey, primary, Veronese, Silvio, primary, Tzenou, Tatiana, primary, Karan-Djurasevic, Teodora, primary, Catherwood, Mark, primary, Kienle, Dirk, primary, Chatzouli, Maria, primary, Facco, Monica, primary, Bahlo, Jasmin, primary, Pott, Christiane, primary, Pedersen, Lone Bredo, primary, Mansouri, Larry, primary, Smedby, Karin E., primary, Chu, Charles C., primary, Giudicelli, Véronique, primary, Lefranc, Marie-Paule, primary, Panagiotidis, Panagiotis, primary, Juliusson, Gunnar, primary, Anagnostopoulos, Achilles, primary, Vlahavas, Ioannis, primary, Antic, Darko, primary, Trentin, Livio, primary, Montillo, Marco, primary, Niemann, Carsten, primary, Döhner, Hartmut, primary, Langerak, Anton W., primary, Pospisilova, Sarka, primary, Hallek, Michael, primary, Campo, Elias, primary, Chiorazzi, Nicholas, primary, Maglaveras, Nikos, primary, Oscier, David, primary, Gaidano, Gianluca, primary, Jelinek, Diane F., primary, Stilgenbauer, Stephan, primary, Chouvarda, Ioanna, primary, Darzentas, Nikos, primary, Belessi, Chrysoula, primary, Davi, Frederic, primary, Hadzidimitriou, Anastasia, primary, Rosenquist, Richard, primary, Ghia, Paolo, primary, and Stamatopoulos, Kostas, primary

Published
2023
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11. Soft tissue lesion of the oral cavity

Author

Overweel, F. P., Rutgers, Robert, Budel, Leo M., Sandberg, Yorick, Overweel, F. P., Rutgers, Robert, Budel, Leo M., and Sandberg, Yorick

Published
2023

12. A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

Author

MS Hematologie, Cancer, Infection & Immunity, de Jonge, A. Vera, van Werkhoven, Erik, Dinmohamed, Avinash G., Nijland, Marcel, Zwinderman, Aeilko H., Bossuyt, Patrick M., Veldhuis, Martine S., Rutten, Emma G.G.M., Mous, Rogier, Vermaat, Joost S.P., Sandberg, Yorick, de Jongh, Eva, Bilgin, Yavuz M., Boersma, Rinske, Koene, Harry, Kersten, Marie José, de Jong, Daphne, Chamuleau, Martine E.D., MS Hematologie, Cancer, Infection & Immunity, de Jonge, A. Vera, van Werkhoven, Erik, Dinmohamed, Avinash G., Nijland, Marcel, Zwinderman, Aeilko H., Bossuyt, Patrick M., Veldhuis, Martine S., Rutten, Emma G.G.M., Mous, Rogier, Vermaat, Joost S.P., Sandberg, Yorick, de Jongh, Eva, Bilgin, Yavuz M., Boersma, Rinske, Koene, Harry, Kersten, Marie José, de Jong, Daphne, and Chamuleau, Martine E.D.

Published
2023

15. Immune Profiling of Double and Triple Hit High Grade B Cell Lymphoma Patients Treated with DA-EPOCH Reveals Activation of T Cells and Reduced T Cell Exhaustion

Author

de Jonge, A.Vera, primary, Duetz, Carolien, additional, Bruins, Wassilis S.C., additional, van Werkhoven, Erik D., additional, Nijland, Marcel, additional, Van Der Poel, Marjolein W.M., additional, de Heer, Koen, additional, Klerk, Clara P.W., additional, Sandberg, Yorick, additional, Fijnheer, Rob, additional, Mutseaers, Pim, additional, Issa, Djamila E., additional, Böhmer, Lara H., additional, Van Kampen, Roel J.W., additional, Visser, Otto J., additional, de Jong, Daphne, additional, Zijlstra, Josée M., additional, Mutis, Tuna, additional, and Chamuleau, Martine E.D., additional

Published
2022
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16. Plasma Extracellular Vesicle-Associated microRNAs for Early Response Prediction in Patients with High-Grade B-Cell Lymphoma

Author

Wang, Steven, primary, Drees, Esther E.E., additional, Gómez-Martín, Cristina, additional, De Jonge, A., additional, van Eijndhoven, Monique, additional, Groenewegen, Nils, additional, Veldt-Verkuijlen, Sandra, additional, Nijland, Marcel, additional, Van Der Poel, Marjolein W.M., additional, Sandberg, Yorick, additional, van Rijn, Rozemarijn, additional, Mutsaers, Pim, additional, Vergote, Vibeke K.J., additional, Kersten, Marie José, additional, Bilgin, Yavuz M., additional, Stevens, Wendy B.C., additional, Durian, Marc, additional, Snijders, Tjeerd J.F., additional, de Jong, Daphne, additional, Zijlstra, Josée M., additional, Chamuleau, Martine E.D., additional, and Pegtel, Dirk Michiel, additional

Published
2022
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17. A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC-Rearranged DLBCL Patients

Author

de Jonge, A. Vera, primary, van Werkhoven, Erik D., additional, Dinmohamed, Avinash G., additional, Nijland, Marcel, additional, Zwinderman, Aeilko H., additional, Bossuyt, Patrick M., additional, Veldhuis, Martine S., additional, Rutten, Emma G.G.M., additional, Mous, Rogier, additional, Vermaat, Joost S.P., additional, Sandberg, Yorick, additional, de Jongh, Eva, additional, Bilgin, Yavuz M., additional, Boersma, Rinske, additional, Koene, Harry R., additional, Kersten, Marie Jose, additional, de Jong, Daphne, additional, and Chamuleau, Martine E.D., additional

Published
2022
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18. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study

Author

Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Agathangelidis, Andreas, Nichelatti, Michele, Tsanousa, Athina, Scarfò, Lydia, Davis, Zadie, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjogra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C, Veronese, Silvio, Gardiner, Anne, Mansouri, Larry, Smedby, Karin E, Pedersen, Lone Bredo, van Lom, Kirsten, Giudicelli, Véronique, Francova, Hana Skuhrova, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H, Langerak, Anton W, Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Published
2014
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19. Een man met jeuk en roodheid van de huid

Author

Overweel, Anne F P, Langerak, Anton W, Damman, Jeffrey, de Haas, Ellen L M, Weerkamp, Floor, Sandberg, Yorick, Erasmus MC other, Immunology, Pathology, Dermatology, and Hematology

Abstract

BACKGROUND: Erythroderma could be the first sign of a cutaneous T-cell lymphoma (CTCL), such as Sézary syndrome. Causes of erythroderma include inflammatory dermatosis, toxicoderma, paraneoplastic erytroderma, and CTCL. Hence, diagnosing Sézary syndrome can be difficult. Sézary syndrome is a rare, aggressive disease characterized by erythroderma, generalized lymphadenopathy and the presence of clonally related neoplastic T-cells in skin, peripheral blood, and lymph nodes. Treatment consists of photochemotherapy (PUVA), radiotherapy, immunomodulatory agents, low dose cytotoxic agents, and intensive chemotherapy. Immunotherapy directed against CCR4 and PD1 are new, promising developments. CASE DESCRIPTION: A 51-year-old man presented with a 1-year history of progressive, itchy erythroderma and lymphocytosis. After extensive cytomorphological, histopathological and molecular examination the diagnosis of Sézary syndrome could be established. Combination treatment of interferon and photochemotherapy (PUVA) was started. CONCLUSION: Diagnostic delay in Sézary syndrome is common. Integrated cytomorphological, immunological, and molecular evaluation of peripheral blood in patients with unexplained erythroderma non-responsive to (topical) treatment is warranted.

Published
2022

20. miR-181a is a novel player in the STAT3-mediated survival network of TCRαβ+ CD8+ T large granular lymphocyte leukemia

Author

Assmann, Jorn L. J. C., primary, Leon, Leticia G., additional, Stavast, Christiaan J., additional, van den Bogaerdt, Sanne E., additional, Schilperoord-Vermeulen, Joyce, additional, Sandberg, Yorick, additional, Bellido, Mar, additional, Erkeland, Stefan J., additional, Feith, David J., additional, Loughran Jr, Thomas P., additional, and Langerak, Anton W., additional

Published
2021
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21. High Grade B Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements Treated with DA-EPOCH-R Induction and Nivolumab Consolidation Treatment: Interim Results of the HOVON-152 Phase II Trial

Author

de Jonge, A. Vera, primary, van Werkhoven, Erik D., additional, Nijland, Marcel, additional, de Heer, Koen, additional, Van Der Poel, Marjolein W.M., additional, Sandberg, Yorick, additional, Klerk, Clara, additional, Drees, Esther E.E., additional, Roemer, Margaretha GM, additional, de Jong, Daphne, additional, Pegtel, D. Michiel, additional, van der Holt, Bronno, additional, Mutis, Tuna, additional, Zijlstra, Josée M, additional, Kersten, Marie José, additional, and Chamuleau, Martine E.D, additional

Published
2021
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23. Generating human prostate cancer organoids from leukapheresis enriched circulating tumour cells

Author

Mout, Lisanne, primary, van Dessel, Lisanne F., additional, Kraan, Jaco, additional, de Jong, Anouk C., additional, Neves, Rui P.L., additional, Erkens-Schulze, Sigrun, additional, Beaufort, Corine M., additional, Sieuwerts, Anieta M., additional, van Riet, Job, additional, Woo, Thomas L.C., additional, de Wit, Ronald, additional, Sleijfer, Stefan, additional, Hamberg, Paul, additional, Sandberg, Yorick, additional, te Boekhorst, Peter A.W., additional, van de Werken, Harmen J.G., additional, Martens, John W.M., additional, Stoecklein, Nikolas H., additional, van Weerden, Wytske M., additional, and Lolkema, Martijn P., additional

Published
2021
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24. Generating human prostate cancer organoids from leukapheresis enriched circulating tumour cells

Author

Mout, Lisanne, van Dessel, Lisanne F., Kraan, Jaco, de Jong, Anouk C., Neves, Rui P.L., Erkens-Schulze, Sigrun, Beaufort, Corine M., Sieuwerts, Anieta M., van Riet, Job, Woo, Thomas L.C., de Wit, Ronald, Sleijfer, Stefan, Hamberg, Paul, Sandberg, Yorick, te Boekhorst, Peter A.W., van de Werken, Harmen J.G., Martens, John W.M., Stoecklein, Nikolas H., van Weerden, Wytske M., Lolkema, Martijn P., Mout, Lisanne, van Dessel, Lisanne F., Kraan, Jaco, de Jong, Anouk C., Neves, Rui P.L., Erkens-Schulze, Sigrun, Beaufort, Corine M., Sieuwerts, Anieta M., van Riet, Job, Woo, Thomas L.C., de Wit, Ronald, Sleijfer, Stefan, Hamberg, Paul, Sandberg, Yorick, te Boekhorst, Peter A.W., van de Werken, Harmen J.G., Martens, John W.M., Stoecklein, Nikolas H., van Weerden, Wytske M., and Lolkema, Martijn P.

Abstract

Background: Circulating tumour cell (CTC)–derived organoids have the potential to provide a powerful tool for personalised cancer therapy but are restrained by low CTC numbers provided by blood samples. Here, we used diagnostic leukapheresis (DLA) to enrich CTCs from patients with metastatic prostate cancer (mPCa) and explored whether organoids provide a platform for ex vivo treatment modelling. Methods: We prospectively screened 102 patients with mPCa and performed DLA in 40 patients with ≥5 CTCs/7.5 mL blood. We enriched CTCs from DLA using white blood cell (WBC) depletion alone or combined with EpCAM selection. The enriched CTC samples were cultured in 3D to obtain organoids and used for downstream analyses. Results: The DLA procedure resulted in a median yield of 5312 CTCs as compared with 22 CTCs in 7.5 mL of blood. Using WBC depletion, we recovered 46% of the CTCs, which reduced to 12% with subsequent EpCAM selection. From the isolated and enriched CTC samples, organoid expansion succeeded in 35%. Successful organoid cultures contained significantly higher CTC numbers at initiation. Moreover, we performed treatment modelling in one organoid cell line and identified substantial tumour heterogeneity in CTCs using single cell DNA sequencing. Conclusions: DLA is an efficient method to enrich CTCs, although the modest success rate of culturing CTCs precludes large scale clinical application. Our data do suggest that DLA and subsequent processing provides a rich source of viable tumour cells. Therefore, DLA offers a promising alternative to biopsy procedures to obtain sufficient number of tumour cells to study sequential samples in patients with mPCa. Trial registration number: NL6019.

Published
2021

25. DA-EPOCH-R for High Grade B-Cell Lymphoma Patients with MYC and BCL2 and/or BCL6 Rearrangements: Clinical Results of the Induction Phase of the HOVON-152 Trial

Author

de Jonge, A.Vera, Kersten, Marie José, van Werkhoven, Erik, van der Poel, Marjolein, de Heer, Koen, Klerk, Clara, Sandberg, Yorick, Van Rijn, Rozemarijn S, Fijnheer, Rob, Mutsaers, Pim, Vergote, Vibeke, Issa, Djamila, Beeker, Aart, Bilgin, Yavuz M., Böhmer, Lara H., Nieuwenhuizen, Laurens, Stevens, Wendy, van Kampen, Roel JW, Mous, Rogier, Durian, Marc, Snijders, Tjeerd, Vermaat, Joost S.P, Visser, Otto, Zijlstra, Josée M., Hofwegen, Henk, Zanders, Helma G.J.M., Fu, Liping P., De Jong, Daphne, Nijland, Marcel, and Chamuleau, Martine E.D.

Published
2023
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29. Acquired haemophilia A after alemtuzumab therapy

Author

van der Zwan, Marieke, Leebeek, Frank W.G., Sandberg, Yorick, Kruip, Marieke J.H.A., Hesselink, Dennis A., van der Zwan, Marieke, Leebeek, Frank W.G., Sandberg, Yorick, Kruip, Marieke J.H.A., and Hesselink, Dennis A.

Published
2020

30. Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients

Author

Man, Femke M., primary, Eerden, Ruben A.G., additional, Doorn, Gerdien M., additional, Oomen‐de Hoop, Esther, additional, Koolen, Stijn L.W., additional, Olieman, Joanne F., additional, Bruijn, Peter, additional, Veraart, Joris N., additional, Halteren, Henk K., additional, Sandberg, Yorick, additional, Moelker, Adriaan, additional, IJzermans, Jan N.M., additional, Lolkema, Martijn P., additional, Gelder, Teun, additional, Dollé, Martijn E.T., additional, Bruin, Ron W.F., additional, and Mathijssen, Ron H.J., additional

Published
2020
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33. Abstract 3919: Liquid biopsy derived organoids as a potential platform for personalized cancer therapy in metastatic prostate cancer

Author

Mout, Lisanne, primary, van Dessel, Lisanne F., additional, Kraan, Jaco, additional, de Jong, Anouk C., additional, Neves, Rui P., additional, Erkens-Schulze, Sigrun, additional, Siewerts, Anieta M., additional, van Riet, Job, additional, de Wit, Ronald, additional, Sleijfer, Stefan, additional, Hamberg, Paul, additional, Sandberg, Yorick, additional, te Boekhorst, Peter A., additional, van de Werken, Harmen J., additional, Martens, John W., additional, Stoecklein, Nikolas H., additional, van Weerden, Wytske M., additional, and Lolkema, Martijn P., additional

Published
2020
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41. Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients.

Author

Man, Femke M., Eerden, Ruben A.G., Doorn, Gerdien M., Oomen‐de Hoop, Esther, Koolen, Stijn L.W., Olieman, Joanne F., Bruijn, Peter, Veraart, Joris N., Halteren, Henk K., Sandberg, Yorick, Moelker, Adriaan, IJzermans, Jan N.M., Lolkema, Martijn P., Gelder, Teun, Dollé, Martijn E.T., Bruin, Ron W.F., and Mathijssen, Ron H.J.

Subjects
LOW-calorie diet, IRINOTECAN, CANCER patients, LIVER metastasis, FEBRILE neutropenia
Abstract

Preclinical data suggests that protein and calorie restriction (PCR) might improve treatment tolerability without impairing antitumor efficacy. Therefore, we have studied the influence of PCR on irinotecan pharmacokinetics and toxicity. In this crossover trial, patients with liver metastases of solid tumors were included and randomized to treatment with irinotecan preceded by 5 days of PCR (~ 30% caloric and ~ 70% protein restriction) during the first cycle and a second cycle preceded by a normal diet or vice versa. Pharmacokinetic blood sampling and biopsies of both healthy liver and liver metastases were performed. The primary end point was the relative difference in geometric means for the active metabolite SN‐38 concentration in healthy liver analyzed by a linear mixed model. No significant differences were seen in irinotecan (+ 16.8%, P = 0.22) and SN‐38 (+ 9.8%, P = 0.48) concentrations between PCR and normal diet in healthy liver, as well as in liver metastases (irinotecan: −38.8%, P = 0.05 and SN‐38: −13.8%, P = 0.50). PCR increased irinotecan plasma area under the curve from zero to 24 hours (AUC0–24h) with 7.1% (P = 0.04) compared with normal diet, whereas the SN‐38 plasma AUC0–24h increased with 50.3% (P < 0.001). Grade ≥ 3 toxicity was not increased during PCR vs. normal diet (P = 0.69). No difference was seen in neutropenia grade ≥ 3 (47% vs. 32% P = 0.38), diarrhea grade ≥ 3 (5% vs. 21% P = 0.25), and febrile neutropenia (5% vs. 16% P = 0.50) during PCR vs. normal diet. In conclusion, plasma SN‐38 exposure increased dramatically after PCR, whereas toxicity did not change. PCR did not alter the irinotecan and SN‐38 exposure in healthy liver and liver metastases. PCR might therefore potentially improve the therapeutic window in patients treated with irinotecan. [ABSTRACT FROM AUTHOR]

Published
2021
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42. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Baliakas, Panagiotis, Mattsson, Mattias, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andreas, Sutton, Lesley Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J., Tzenou, Tatiana, Chu, Charles C., Veronese, Silvio, Mansouri, Larry, Smedby, Karin E., Giudicelli, Veronique, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U., Langerak, Anton W., Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Shanafelt, Tait, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, Baliakas, Panagiotis, Mattsson, Mattias, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andreas, Sutton, Lesley Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J., Tzenou, Tatiana, Chu, Charles C., Veronese, Silvio, Mansouri, Larry, Smedby, Karin E., Giudicelli, Veronique, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U., Langerak, Anton W., Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Shanafelt, Tait, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, and Stamatopoulos, Kostas

Published
2018
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43. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Baliakas, P, Mattsson, M, Hadzidimitriou, A, Minga, E, Agathangelidis, A, Sutton, LA, Scarfo, L, Davis, Z, Yan, XJ, Plevova, K, Sandberg, Yorick, Vojdeman, FJ, Tzenou, T, Chu, CC, Veronese, S, Mansouri, L, Smedby, KE, Giudicelli, V, Nguyen-Khac, F, Panagiotidis, P, Juliusson, G, Anagnostopoulos, A, Lefranc, MP, Trentin, L, Catherwood, M, Montillo, M, Niemann, CU, Langerak, Ton, Pospisilova, S, Stavroyianni, N, Chiorazzi, N, Oscier, D, Jelinek, DF, Shanafelt, T, Darzentas, N, Belessi, C, Davi, F, Ghia, P, Rosenquist, R, Stamatopoulos, K, Baliakas, P, Mattsson, M, Hadzidimitriou, A, Minga, E, Agathangelidis, A, Sutton, LA, Scarfo, L, Davis, Z, Yan, XJ, Plevova, K, Sandberg, Yorick, Vojdeman, FJ, Tzenou, T, Chu, CC, Veronese, S, Mansouri, L, Smedby, KE, Giudicelli, V, Nguyen-Khac, F, Panagiotidis, P, Juliusson, G, Anagnostopoulos, A, Lefranc, MP, Trentin, L, Catherwood, M, Montillo, M, Niemann, CU, Langerak, Ton, Pospisilova, S, Stavroyianni, N, Chiorazzi, N, Oscier, D, Jelinek, DF, Shanafelt, T, Darzentas, N, Belessi, C, Davi, F, Ghia, P, Rosenquist, R, and Stamatopoulos, K

Published
2018

46. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Baliakas, Panagiotis, primary, Mattsson, Mattias, additional, Hadzidimitriou, Anastasia, additional, Minga, Eva, additional, Agathangelidis, Andreas, additional, Sutton, Lesley-Ann, additional, Scarfo, Lydia, additional, Davis, Zadie, additional, Yan, Xiao-Jie, additional, Plevova, Karla, additional, Sandberg, Yorick, additional, Vojdeman, Fie J., additional, Tzenou, Tatiana, additional, Chu, Charles C., additional, Veronese, Silvio, additional, Mansouri, Larry, additional, Smedby, Karin E, additional, Giudicelli, Véronique, additional, Nguyen-Khac, Florence, additional, Panagiotidis, Panagiotis, additional, Juliusson, Gunnar, additional, Anagnostopoulos, Achilles, additional, Lefranc, Marie-Paule, additional, Trentin, Livio, additional, Catherwood, Mark, additional, Montillo, Marco, additional, Niemann, Carsten U., additional, Langerak, Anton W., additional, Pospisilova, Sarka, additional, Stavroyianni, Niki, additional, Chiorazzi, Nicholas, additional, Oscier, David, additional, Jelinek, Diane F, additional, Shanafelt, Tait, additional, Darzentas, Nikos, additional, Belessi, Chrysoula, additional, Davi, Frederic, additional, Ghia, Paolo, additional, Rosenquist, Richard, additional, and Stamatopoulos, Kostas, additional

Published
2017
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47. Dysregulated signaling, proliferation and apoptosis impact on the pathogenesis of TCRγδ+ T cell large granular lymphocyte leukemia

Author

Kallemeijn, Martine J., Ridder, Dick, de, Schilperoord-Vermeulen, Joyce, Klift, Michèle Y., van der, Sandberg, Yorick, Dongen, Jacques J.M., van, Langerak, Anton W., Kallemeijn, Martine J., Ridder, Dick, de, Schilperoord-Vermeulen, Joyce, Klift, Michèle Y., van der, Sandberg, Yorick, Dongen, Jacques J.M., van, and Langerak, Anton W.

Abstract

TCRγδ+ T-LGL leukemia is a rare form of chronic mature T cell disorders in elderly, which is generally characterized by a persistently enlarged CD3+CD57+TCRγδ+ large granular lymphocyte population in the peripheral blood with a monoclonal phenotype. Clinically, the disease is heterogeneous, most patients being largely asymptomatic, although neutropenia, fatigue and B symptoms and underlying diseases such as autoimmune diseases or malignancies are also often observed. The etiology of TCRγδ+ T-LGL proliferations is largely unknown. Here, we aimed to investigate underlying molecular mechanisms of these rare proliferations by performing gene expression profiling of TCRγδ+ T-LGL versus normal TCRγδ+ T cell subsets. From our initial microarray dataset we observed that TCRγδ+ TLGL leukemia forms a separate group when compared with different healthy control TCRγδ + T cell subsets, correlating best with the healthy TemRA subset. The lowest correlation was seen with the naive subset. Based on specific comparison between healthy control cells and TCRγδ+ T-LGL leukemia cells we observed up-regulation of survival, proliferation and hematopoietic system related genes, with a remarkable down-regulation of apoptotic pathway genes. RQ-PCR validation of important genes representative for the dataset, including apoptosis (XIAP, CASP1, BCLAF1 and CFLAR), proliferation/development (ID3) and inflammation (CD28, CCR7, CX3CR1 and IFNG) processes largely confirmed the dysregulation in proliferation and apoptosis. Based on these expression data we conclude that TCRγδ+ T-LGL leukemia is likely the result of an underlying aberrant molecular mechanisms leading to increased proliferation and reduced apoptosis.

Published
2017

48. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors : Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

Xochelli, Aliki, Baliakas, Panagiotis, Kavakiotis, Ioannis, Agathangelidis, Andreas, Sutton, Lesley Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E., Chu, Charles C., Giudicelli, Veronique, Lefranc, Marie-Paule, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Vlahavas, Ioannis, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Doehner, Hartmut, Langerak, Anton W., Pospisilova, Sarka, Hallek, Michael, Campo, Elias, Chiorazzi, Nicholas, Maglaveras, Nikos, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F., Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, Xochelli, Aliki, Baliakas, Panagiotis, Kavakiotis, Ioannis, Agathangelidis, Andreas, Sutton, Lesley Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E., Chu, Charles C., Giudicelli, Veronique, Lefranc, Marie-Paule, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Vlahavas, Ioannis, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Doehner, Hartmut, Langerak, Anton W., Pospisilova, Sarka, Hallek, Michael, Campo, Elias, Chiorazzi, Nicholas, Maglaveras, Nikos, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F., Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Abstract

Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.

Published
2017
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