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1. Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Author

Hilberink, Jacobien R., van Zeventer, Isabelle A., Chitu, Dana A., Pabst, Thomas, Klein, Saskia K., Stussi, Georg, Griskevicius, Laimonas, Valk, Peter J. M., Cloos, Jacqueline, van de Loosdrecht, Arjan A., Breems, Dimitri, van Lammeren-Venema, Danielle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G., Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W. M., Legdeur, Marie Cecile, Tick, Lidwine, Chalandon, Yves, Ammatuna, Emanuele, Blum, Sabine, Löwenberg, Bob, Ossenkoppele, Gert J., and Huls, Gerwin

Published
2023
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3. 10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial

Author

Finke, Jürgen, Schaap, Nicolaas Petrus Michael, Zucenka, Andrius, Metzelder, Stephan, Jost, Edgar, Perić, Zinaida, Forghieri, Fabio, Allione, Bernadino, Martelli, Maurizio, Iori, Anna Paola, Wittnebel, Sebastian, Mengarelli, Andrea, Imovilli, Annalisa, Olivieri, Attilio, De Prijck, Bernard José Marie, van der Poel, Marjolein W.M., Junghanß, Christian, Salih, Helmut Rainer, Tafuri, Agostino, Guimarães, José Eduardo, Musso, Maurizio, De Fabritiis, Paolo, Chevallier, Patrice, Selleslag, Dominik Luc, Cascavilla, Nicola, Berneman, Zwi, Jaspers, Aurélie, Zuffa, Eliana, Vanstraelen, Gaëtan, Visani, Giuseppe, Cuijpers, Maria Louisa Henriëtte, De Becker, Ann, Mianulli, Anna Maria, Hackanson, Björn, Mihaylov, Georgi Georgiev, Martinelli, Giovanni, Paolini, Stefania, Zinzani, Pier Luigi, Henkes, Martin, Al-Ali, Haifa Kathrin, La Rosée, Paul, Chierichini, Anna, Cudillo, Laura, Specchia, Giorgina, Šimec, Njetočka Gredelj, Capalbo, Silvana Franca, Spinosa, Giuseppina, Molica, Stefano, de Jonge-Peeters, Susan Dorothé, Lübbert, Michael, Wijermans, Pierre W, Kicinski, Michal, Chantepie, Sylvain, Van der Velden, Walter J F M, Noppeney, Richard, Griškevičius, Laimonas, Neubauer, Andreas, Crysandt, Martina, Vrhovac, Radovan, Luppi, Mario, Fuhrmann, Stephan, Audisio, Ernesta, Candoni, Anna, Legrand, Olivier, Foà, Robin, Gaidano, Gianluca, van Lammeren-Venema, Danielle, Posthuma, Eduardus F M, Hoogendoorn, Mels, Giraut, Anne, Stevens-Kroef, Marian, Jansen, Joop H, de Graaf, Aniek O, Efficace, Fabio, Ammatuna, Emanuele, Vilque, Jean-Pierre, Wäsch, Ralph, Becker, Heiko, Blijlevens, Nicole, Dührsen, Ulrich, Baron, Frédéric, Suciu, Stefan, Amadori, Sergio, Venditti, Adriano, and Huls, Gerwin

Published
2023
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4. Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL

Author

Beckers, M. M. J., Bekker, A., Bellido, M., de Boer, F., Broers, R., Chamuleau, M., Croockewit, A. J., Dompeling, E. C., Eefting, M., van Gelder, M., Hoogendoorn, M., Houtenbos, I., Doorduijn, J. K., Droogendijk, J., van der Griend, R., de Heer, K., Henkens, C. M. A., Idink, C. A. M., Issa, D. E., van Kampen, R., Kater, A. P., Kersting, S., van der Klift, M., Laterveer, L., Levenga, H., Levin, M-D., Mous, R., Nijland, M., Nijziel, M., van Norden, Y., Posthuma, E. F. M., te Raa, G. D., Raymakers, R. A. P., Regelink, J. C., Sandberg, Y., Schaafsma, M. R., Silbermann, M. H., van der Spek, A. C., van der Straaten, H. M., Tanis, B., Terpstra, W. E., Tick, L. W., Tonino, S. H., Veelken, J. H., Velders, G. A., Vlasveld, L., Visser, H. P. J., Vos, J. M. I., Wittebol, S., van Zaanen, H. C. T., van der Straten, Lina, Stege, Claudia A. M., Kersting, Sabina, Nasserinejad, Kazem, Dubois, Julie, Dobber, Johan A., Mellink, Clemens H. M., van der Kevie-Kersemaekers, Anne-Marie F., Evers, Ludo M., de Boer, Fransien, Koene, Harry R., Schreurs, John, van der Klift, Marjolein, Velders, Gerjo A., van der Spek, Ellen, van der Straaten, Hanneke M., Hoogendoorn, Mels, van Gelder, Michel, Posthuma, Eduardus F. M., Visser, Hein P. J., Houtenbos, Ilse, Idink, Cecile A. M., Issa, Djamila E., Dompeling, Ellen C., van Zaanen, Henk C. T., Veelken, J. Hendrik, Levenga, Henriette, Tick, Lidwine W., Terpstra, Wim E., Tonino, Sanne H., Westerweel, Peter E., Langerak, Anton W., Kater, Arnon P., and Levin, Mark-David

Published
2023
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7. Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial

Author

Kersting, Sabina, Dubois, Julie, Nasserinejad, Kazem, Dobber, Johan A, Mellink, Clemens, van der Kevie-Kersemaekers, Anne-Marie F, Evers, Ludo M, de Boer, Fransien, Koene, Harry R, Schreurs, John, van der Klift, Marjolein, Velders, Gerjo A, van der Spek, Ellen, van der Straaten, Hanneke M, Hoogendoorn, Mels, van Gelder, Michel, Posthuma, Eduardus F M, Visser, Hein P J, Houtenbos, Ilse, Idink, Cecile A M, Issa, Djamila E, Dompeling, Ellen C, van Zaanen, Henk C T, Veelken, Hendrik, Levenga, Henriette, Tick, Lidwine W, Terpstra, Wim E, Tonino, Sanne H, Boyer, Michelle, Mobasher, Mehrdad, Levin, Mark-David, and Kater, Arnon P

Published
2022
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8. Improving the identification of frail elderly newly diagnosed multiple myeloma patients

Author

Stege, Claudia A. M., Nasserinejad, Kazem, Klein, Saskia K., Timmers, Gert-Jan, Hoogendoorn, Mels, Ypma, Paula F., Nijhof, Inger S., Velders, Gerjo A., Strobbe, Leonie, Durdu-Rayman, Nazik, Westerman, Matthijs, Davidis-van Schoonhoven, Marjan A., van Kampen, Roel J. W., Beeker, Aart, Koster, Ad, Dijk, Amanda C., van de Donk, Niels W. C. J., van der Spek, Ellen, Leys, Rineke B. L., Silbermann, Matthijs H., Groen, Kaz, van der Burg-de Graauw, Nicole C. H. P., Sinnige, Harm A. M., van der Hem, Klaas G., Levenga, Henriette, Bilgin, Yavuz M., Sonneveld, Pieter, Levin, Mark-David, and Zweegman, Sonja

Published
2021
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9. Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL

Author

van der Straten, Lina, primary, Stege, Claudia A. M., additional, Kersting, Sabina, additional, Nasserinejad, Kazem, additional, Dubois, Julie, additional, Dobber, Johan A., additional, Mellink, Clemens H. M., additional, van der Kevie-Kersemaekers, Anne-Marie F., additional, Evers, Ludo M., additional, de Boer, Fransien, additional, Koene, Harry R., additional, Schreurs, John, additional, van der Klift, Marjolein, additional, Velders, Gerjo A., additional, van der Spek, Ellen, additional, van der Straaten, Hanneke M., additional, Hoogendoorn, Mels, additional, van Gelder, Michel, additional, Posthuma, Eduardus F. M., additional, Visser, Hein P. J., additional, Houtenbos, Ilse, additional, Idink, Cecile A. M., additional, Issa, Djamila E., additional, Dompeling, Ellen C., additional, van Zaanen, Henk C. T., additional, Veelken, J. Hendrik, additional, Levenga, Henriette, additional, Tick, Lidwine W., additional, Terpstra, Wim E., additional, Tonino, Sanne H., additional, Westerweel, Peter E., additional, Langerak, Anton W., additional, Kater, Arnon P., additional, and Levin, Mark-David, additional

Published
2023
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10. BCR::ABL1 kinase domain mutation testing and clinical outcome in a nationwide chronic myeloid leukemia patient population

Author

Kockerols, Camille, primary, Valk, Peter J. M., additional, Blijlevens, Nicole M. A., additional, Cornelissen, Jan J., additional, Dinmohamed, Avinash G., additional, Geelen, Inge, additional, Hoogendoorn, Mels, additional, Janssen, Jeroen J. W. M., additional, Daenen, Laura G. M., additional, Reijden, Bert A. van der, additional, and Westerweel, Peter E., additional

Published
2023
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12. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia

Author

Eichhorst, Barbara, primary, Niemann, Carsten U., additional, Kater, Arnon P., additional, Fürstenau, Moritz, additional, von Tresckow, Julia, additional, Zhang, Can, additional, Robrecht, Sandra, additional, Gregor, Michael, additional, Juliusson, Gunnar, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Lindström, Vesa, additional, da Cunha-Bang, Caspar, additional, Schneider, Christof, additional, Poulsen, Christian B., additional, Illmer, Thomas, additional, Schöttker, Björn, additional, Nösslinger, Thomas, additional, Janssens, Ann, additional, Christiansen, Ilse, additional, Baumann, Michael, additional, Frederiksen, Henrik, additional, van der Klift, Marjolein, additional, Jäger, Ulrich, additional, Leys, Maria B.L., additional, Hoogendoorn, Mels, additional, Lotfi, Kourosh, additional, Hebart, Holger, additional, Gaska, Tobias, additional, Koene, Harry, additional, Enggaard, Lisbeth, additional, Goede, Jereon, additional, Regelink, Josien C., additional, Widmer, Anouk, additional, Simon, Florian, additional, De Silva, Nisha, additional, Fink, Anna-Maria, additional, Bahlo, Jasmin, additional, Fischer, Kirsten, additional, Wendtner, Clemens-Martin, additional, Kreuzer, Karl A., additional, Ritgen, Matthias, additional, Brüggemann, Monika, additional, Tausch, Eugen, additional, Levin, Mark-David, additional, van Oers, Marinus, additional, Geisler, Christian, additional, Stilgenbauer, Stephan, additional, and Hallek, Michael, additional

Published
2023
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13. Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Author

Hilberink, Jacobien R, van Zeventer, Isabelle A, Chitu, Dana A, Pabst, Thomas, Klein, Saskia K, Stussi, Georg, Griskevicius, Laimonas, Valk, Peter J M, Cloos, Jacqueline, van de Loosdrecht, Arjan A, Breems, Dimitri, van Lammeren-Venema, Danielle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G, Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W M, Legdeur, Marie Cecile, Tick, Lidwine, Chalandon, Yves, Ammatuna, Emanuele, Blum, Sabine, Löwenberg, Bob, Ossenkoppele, Gert J, and Huls, Gerwin

Subjects
610 Medicine & health
Abstract

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.

Published
2023

15. 10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial

Author

Lübbert, Michael, Wijermans, Pierre W, Kicinski, Michal, Chantepie, Sylvain, Van der Velden, Walter J F M, Noppeney, Richard, Griškevičius, Laimonas, Neubauer, Andreas, Crysandt, Martina, Vrhovac, Radovan, Luppi, Mario, Fuhrmann, Stephan, Audisio, Ernesta, Candoni, Anna, Legrand, Olivier, Foà, Robin, Gaidano, Gianluca, van Lammeren-Venema, Danielle, Posthuma, Eduardus F M, Hoogendoorn, Mels, Giraut, Anne, Stevens-Kroef, Marian, Jansen, Joop H, de Graaf, Aniek O, Efficace, Fabio, Ammatuna, Emanuele, Vilque, Jean-Pierre, Wäsch, Ralph, Becker, Heiko, Blijlevens, Nicole, Dührsen, Ulrich, Baron, Frédéric, Suciu, Stefan, Amadori, Sergio, Venditti, Adriano, Huls, Gerwin, Finke, Jürgen, Schaap, Nicolaas Petrus Michael, Zucenka, Andrius, Metzelder, Stephan, Jost, Edgar, Perić, Zinaida, Forghieri, Fabio, Allione, Bernadino, Martelli, Maurizio, Iori, Anna Paola, Wittnebel, Sebastian, Mengarelli, Andrea, Imovilli, Annalisa, Olivieri, Attilio, De Prijck, Bernard José Marie, van der Poel, Marjolein W.M., Junghanß, Christian, Salih, Helmut Rainer, Tafuri, Agostino, Guimarães, José Eduardo, Musso, Maurizio, De Fabritiis, Paolo, Chevallier, Patrice, Selleslag, Dominik Luc, Cascavilla, Nicola, Berneman, Zwi, Jaspers, Aurélie, Zuffa, Eliana, Vanstraelen, Gaëtan, Visani, Giuseppe, Cuijpers, Maria Louisa Henriëtte, De Becker, Ann, Mianulli, Anna Maria, Hackanson, Björn, Mihaylov, Georgi Georgiev, Martinelli, Giovanni, Paolini, Stefania, Zinzani, Pier Luigi, Henkes, Martin, Al-Ali, Haifa Kathrin, La Rosée, Paul, Chierichini, Anna, Cudillo, Laura, Specchia, Giorgina, Šimec, Njetočka Gredelj, Capalbo, Silvana Franca, Spinosa, Giuseppina, Molica, Stefano, and de Jonge-Peeters, Susan Dorothé

Abstract

Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes.

Published
2023
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16. Kinase Domain Mutation Testing and Clinical Outcome in a Nationwide Chronic Myeloid Leukemia Patient Population

Author

Kockerols, Camille C.B., primary, Valk, Peter JM, additional, Blijlevens, Nicole M A, additional, Cornelissen, Jan J., additional, Dinmohamed, Avinash G., additional, Geelen, Inge, additional, Hoogendoorn, Mels, additional, Janssen, Jeroen J.W.M., additional, Daenen, Laura G.M., additional, van der Reijden, Bert A., additional, and Westerweel, Peter E., additional

Published
2022
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20. A clinical effect of disease-modifying treatment on alloimmunisation in transfused patients with myelodysplastic syndromes: data from a population-based study

Author

Rozema, Johanne, Slim, Christiaan L, Veeger, Nic J G M, Kibbelaar, Robby E, de Wit, Harry, van Roon, Eric N, Hoogendoorn, Mels, PharmacoTherapy, -Epidemiology and -Economics, and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Subjects
Transfusion Medicine and Transfusion Complications, Incidence, Myelodysplastic Syndromes, Blood Group Antigens, Humans, Blood Transfusion, Anemia, Hemolytic, Autoimmune
Abstract

BACKGROUND: Alloimmunisation against blood products is an adverse event, causing time-consuming compatibility testing. Current literature has not yet identified the influence of treatment on the risk of alloimmunisation in patients with myelodysplastic syndromes (MDS). MATERIALS AND METHODS: An observational, population-based study, using the HemoBase registry, was performed including all transfused patients who were diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands. Information about transfusion dates, types, and treatment regimens was collected from the health records. Blood products were matched for ABO and Rhesus D. The effect of disease-modifying treatment was estimated with incidence rates and a Cox time-dependent analysis. RESULTS: 233 patients were included in this study, with a median follow-up of 13.0 months. Alloimmunisation occurred in 21 patients (9.0%) and predominantly occurred early in follow-up. Three (5%) and 18 (11%) alloimmunisation events occurred in patients with and without disease-modifying treatment, respectively. The hazard ratio for alloimmunisation without treatment compared to during treatment was 2.7 (95% CI: 0.35-20.0), with incidence rates of 7.18 and 2.41 per 100 patient-years, respectively. DISCUSSION: In a non-selected real-world population of MDS patients receiving blood transfusions, the percentage of patients with alloimmunisation was below 10%. The results of this study support the hypothesis that disease-modifying treatment affects the ability of the immune system to mount an antibody response to non-self blood group antigens.

Published
2022

21. Adherence to quality indicators in chronic myeloid leukemia care: results from a population-based study in The Netherlands.

Author

Ector, Geneviève I.C.G., Geelen, Inge G. P., Dinmohamed, Avinash G., Hoogendoorn, Mels, Westerweel, Peter E., Hermens, Rosella P.M.G., and Blijlevens, Nicole M.A.

Subjects
CHRONIC myeloid leukemia, CHRONIC leukemia, SHOWROOMS, OVERALL survival, SURVIVAL rate, LEUKEMIA
Abstract

Suboptimal guideline adherence in chronic myeloid leukemia (CML) care is associated with worse treatment outcomes. Current study focused on adherence to seven quality indicators (QIs) based on the European Leukemia Network guideline (one diagnostic, one therapeutic, and five monitoring indicators). Data were obtained from population-based registries in the Netherlands of 405 newly diagnosed chronic phase CML patients between January 2008 and April 2013. Compliance rates regarding diagnostic and therapeutic indicator were 83% and 78%, respectively. Monitoring indicators rates were lower: 21–27% for indicators concerning the first year and 58% and 62% for the second and third year, respectively. Noncompliance occurred mostly due to non-timely monitoring. Twenty cases did not comply with any indicator, 6% complied with all indicators. After adjustment for age, overall survival rates did not differ significantly between the groups. Adherence to guideline-based QIs was suboptimal. This demonstrates the evidence-practice gap, shows room for improvement and underscores the need for real-world data. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Web-Based Return of Individual Patient-Reported Outcome Results Among Patients With Lymphoma: Randomized Controlled Trial

Author

Oerlemans, Simone, primary, Arts, Lindy Paulina Johanna, additional, Kieffer, Jacobien M, additional, Prins, Judith, additional, Hoogendoorn, Mels, additional, van der Poel, Marjolein, additional, Koster, Ad, additional, Lensen, Chantal, additional, Stevens, Wendy Bernadina Catharina, additional, Issa, Djamila, additional, Pruijt, Johannes F M, additional, Oosterveld, Margriet, additional, van der Griend, René, additional, Nijziel, Marten, additional, Tick, Lidwine, additional, Posthuma, Eduardus F M, additional, and van de Poll-Franse, Lonneke V, additional

Published
2021
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25. A Randomized Phase III Study of Venetoclax-Based Time-Limited Combination Treatments (RVe, GVe, GIVe) Vs Standard Chemoimmunotherapy (CIT: FCR/BR) in Frontline Chronic Lymphocytic Leukemia (CLL) of Fit Patients: First Co-Primary Endpoint Analysis of the International Intergroup GAIA (CLL13) Trial

Author

Eichhorst, Barbara, primary, Niemann, Carsten, additional, Kater, Arnon P., additional, Fürstenau, Moritz, additional, Von Tresckow, Julia, additional, Zhang, Can, additional, Robrecht, Sandra, additional, Gregor, Michael, additional, Juliusson, Gunnar, additional, Thornton, Patrick, additional, Staber, Philipp B., additional, Tadmor, Tamar, additional, Lindström, Vesa, additional, Da Cunha-Bang, Caspar, additional, Schneider, Christof, additional, Poulsen, Christian Bjørn, additional, Illmer, Thomas, additional, Schöttker, Björn, additional, Janssens, Ann, additional, Christiansen, Ilse, additional, Noesslinger, Thomas, additional, Baumann, Michael, additional, van der Klift, Marjolein, additional, Jaeger, Ulrich, additional, Frederiksen, Henrik, additional, Leijs, Maria B.L., additional, Hoogendoorn, Mels, additional, Lotfi, Kourosh, additional, Hebart, Holger, additional, Gaska, Tobias, additional, Koene, Harry R., additional, Simon, Florian, additional, De Silva, Nisha, additional, Fink, Anna-Maria, additional, Fischer, Kirsten, additional, Wendtner, Clemens-Martin, additional, Kreuzer, Karl-Anton, additional, Ritgen, Matthias, additional, Brüggemann, Monika, additional, Tausch, Eugen, additional, Levin, Mark-David, additional, Van Oers, Marinus H.J., additional, Geisler, Christian H., additional, Stilgenbauer, Stephan, additional, and Hallek, Michael, additional

Published
2021
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27. Clinical view versus guideline adherence in ferritin monitoring and initiating iron chelation therapy in patients with myelodysplastic syndromes.

Author

Rozema, Johanne, van Asten, Ivar, Kwant, Beau, Kibbelaar, Robby E., Veeger, Nic J. G. M., de Wit, Harry, van Roon, Eric N., and Hoogendoorn, Mels

Subjects
CHELATION therapy, MYELODYSPLASTIC syndromes, FERRITIN, IRON, MEDICAL records
Abstract

Objectives: In patients with myelodysplastic syndromes (MDS) with >20 transfusions and ferritin levels >1000 μg/L, international guidelines recommend iron chelation therapy (ICT). The study's objective was to determine guideline adherence and the intensity of ferritin monitoring in clinical practice. Methods: We performed an observational population‐based study using the HemoBase Registry, which contains data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Clinical information on transfusions, ferritin measurements, ICT, and clinical performance as defined by age ≤ 80 years, Charlson Comorbidity Index <2 and lower‐risk MDS was collected from health records. Results: Two hundred and thirty seven of 292 patients (81.1%) received ≥1 transfusion, and 121 (41.4%) received >20 transfusions. In 57 of these 121 patients (47.1%), ferritin measurements were performed at least once. Clinical performance was significantly associated with monitoring ferritin around the 20th transfusion (RR: 2.49, p =.016). Clinical performance was also associated with initiating ICT (RR: 5.99, p <.001). ICT was offered to 22.3% (n = 25) of eligible patients. Conclusions: In this population‐based study, ferritin levels were measured in <50% of MDS patients who received >20 transfusions, and clinical performance was significantly associated with measuring ferritin. Our study suggests that in heavily transfused MDS patients, ferritin monitoring is primarily based on patients' clinical performance rather than guideline recommendations. [ABSTRACT FROM AUTHOR]

Published
2022
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30. Patterns of transfusion burden in an unselected population of patients with myelodysplastic syndromes: A population‐based study.

Author

Rozema, Johanne, van Roon, Eric N., Kibbelaar, Robby E., Veeger, Nic J. G. M., Slim, Christiaan L., de Wit, Harry, and Hoogendoorn, Mels

Subjects
MYELODYSPLASTIC syndromes, FETOFETAL transfusion, ELECTRONIC health records, TREATMENT effectiveness, REGRESSION analysis, ODDS ratio
Abstract

Background: Ineffective hematopoiesis in patients with myelodysplastic syndromes (MDS) often results in transfusion dependence. The burden of frequent transfusions in the real‐world MDS population is largely unknown. Study design and methods: An observational, retrospective, population‐based study, using the HemoBase registry, was performed including all patients diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands with approximately 650,000 inhabitants. Detailed clinical information was collected from the electronic health records. Transfusion burden was classified according to the International Working Group 2018 criteria: not transfusion dependent, low (LTB), or high transfusion burden (HTB). Univariate and multivariable regression analyses were performed. Results: Of 292 patients, 136 (46.6%) had a HTB of ≥8 units/16 weeks and 17 (5.8%) had a LTB of 3–7 units/16 weeks. This was present in all types of MDS patients, but patients aged 75–84 years (odds ratio [OR] 4.02, 95% confidence interval [CI]: 1.84–8.82), high‐risk MDS patients (OR 2.88, 95% CI: 1.08–7.68) and MDS‐EB‐2 patients (OR 7.07, 95% CI: 2.17–22.90) were particularly at risk for a HTB. Discussion This study provides a reliable estimate of the transfusion burden in real‐world MDS patients, with almost half of the patients having a HTB. A HTB was observed in all MDS subtypes and both low‐ and high‐risk MDS. Therefore, we conclude that the entire MDS population might benefit from novel agents that reduce the transfusion need and that might have beneficial effects on patient outcomes and healthcare utilization outcomes. [ABSTRACT FROM AUTHOR]

Published
2021
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31. Depletion of CLL cells by venetoclax treatment reverses oxidative stress and impaired glycolysis in CD4 T cells

Author

van Bruggen, J.A.C., van der Windt, G.J.W., Hoogendoorn, Mels, Dubois, J., Kater, Arnon P., and Peters, F.S.

Abstract

Acquired T-cell dysfunction is characteristic of CLL and is associated with reduced efficacy of T-cell based therapies. A recently described feature of dysfunctional CLL-derived CD8 T cells is reduced metabolic plasticity. To what extend CD4 T cells are affected, and if CD4 T-cell metabolism and function can be restored upon clinical depletion of CLL cells is currently unknown. Here we address these unresolved issues by a comprehensive phenotypic, metabolic, transcriptomic and functional analysis of CD4 T cells of untreated CLL patients, and by analyzing the effects of venetoclax + obinutuzumab on the CD4 population. Resting CD4 T cells derived from CLL patients expressed lower levels of GLUT-1, displayed deteriorated oxidative phosphorylation (OXPHOS) and overall reduced mitochondrial fitness. Upon T-cell stimulation, CLL T cells were unable to initiate glycolysis. Transcriptome analysis revealed that depletion of CLL cells in vitroresulted in upregulation of OXPHOS and glycolysis pathways and restored T-cell function in vitro. Analysis of CD4 T cells from CLL patients prior and after venetoclax + obinutuzumab treatment, which led to effective clearance of CLL in blood and bone marrow, revealed recovery of T-cell activation and restoration of the switch to glycolysis, as well as improved T-cell proliferation. Collectively these data demonstrate that CLL cells impose metabolic restrictions on CD4 T cells which lead to reduced CD4 T-cell functionality. This trial is registered in the Netherlands Trial Registry ID: NTR6043.

Published
2022
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32. A clinical effect of disease-modifying treatment on alloimmunisation in transfused patients with myelodysplastic syndromes: data from a population-based study.

Author

Rozema J, Slim CL, Veeger NJGM, Kibbelaar RE, de Wit H, van Roon EN, and Hoogendoorn M

Subjects
Blood Transfusion, Humans, Incidence, Anemia, Hemolytic, Autoimmune, Blood Group Antigens, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes therapy
Abstract

Background: Alloimmunisation against blood products is an adverse event, causing time-consuming compatibility testing. Current literature has not yet identified the influence of treatment on the risk of alloimmunisation in patients with myelodysplastic syndromes (MDS)., Materials and Methods: An observational, population-based study, using the HemoBase registry, was performed including all transfused patients who were diagnosed with MDS between 2005 and 2017 in Friesland, a province in the Netherlands. Information about transfusion dates, types, and treatment regimens was collected from the health records. Blood products were matched for ABO and Rhesus D. The effect of disease-modifying treatment was estimated with incidence rates and a Cox time-dependent analysis., Results: 233 patients were included in this study, with a median follow-up of 13.0 months. Alloimmunisation occurred in 21 patients (9.0%) and predominantly occurred early in follow-up. Three (5%) and 18 (11%) alloimmunisation events occurred in patients with and without disease-modifying treatment, respectively. The hazard ratio for alloimmunisation without treatment compared to during treatment was 2.7 (95% CI: 0.35-20.0), with incidence rates of 7.18 and 2.41 per 100 patient-years, respectively., Discussion: In a non-selected real-world population of MDS patients receiving blood transfusions, the percentage of patients with alloimmunisation was below 10%. The results of this study support the hypothesis that disease-modifying treatment affects the ability of the immune system to mount an antibody response to non-self blood group antigens.

Published
2022
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