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1. Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy: Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

Author

Spanjaart, Anne Mea, Ljungman, Per, Tridello, Gloria, Schwartz, Juana, Martinez-Cibrián, Nuria, Barba, Pere, Kwon, Mi, Lopez-Corral, Lucia, Martinez-Lopez, Joaquin, Ferra, Christelle, Di Blasi, Roberta, Ghesquieres, Hervé, Mutsaers, Pim, Calkoen, Friso, Jak, Margot, van Doesum, Jaap, Vermaat, Joost S. P., van der Poel, Marjolein, Maertens, Johan, Gambella, Massimiliano, Metafuni, Elisabetta, Ciceri, Fabio, Saccardi, Riccardo, Nicholson, Emma, Tholouli, Eleni, Matthew, Collin, Potter, Victoria, Bloor, Adrian, Besley, Caroline, Roddie, Claire, Wilson, Keith, Nagler, Arnon, Campos, Antonio, Petersen, Soeren Lykke, Folber, Frantisek, Bader, Peter, Finke, Jurgen, Kroger, Nicolaus, Knelange, Nina, de La Camara, Rafael, Kersten, Marie José, and Mielke, Stephan

Published
2024
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2. Real-world experience with targeted therapy in patients with histiocytic neoplasms in the Netherlands and in Belgium

Author

Beckers, Erik, van den Berg, Merlijn, van den Bos, Cor, de Bree, Godelieve, Buddingh, Emmeline, Claeys, Kristl, van Daele, Paul, De Haes, Petra, Demandt, Astrid, van Dorp, Suzanne, Hak, Liesbeth, van Halteren, Astrid, van der Houwen, Tim, Jak, Margot, Kerstens, Jeroen, Kwakernaak, Arjan, van Laar, Jan, Leavis, Helen, Leguit, Roos, van de Loosdrecht, Arjan, Morsink, Linde, Mous, Rogier, van Noesel, Max, Oostvogels, Rimke, Potjewijd, Judith, Plattel, Wouter, Roeloffzen, Wilfried, Rutgers, Abraham, Tonino, Sanne, Tousseyn, Thomas, Verdijk, Rob, Vermaat, Joost, Woei-A-Jin, Sherida, Kemps, Paul G., Woei-A-Jin, F. J. Sherida H., Schöffski, Patrick, Vanden Bempt, Isabelle, Meyer-Wentrup, Friederike A. G., Dors, Natasja, van Eijkelenburg, Natasha K. A., Scheijde-Vermeulen, Marijn A., Jazet, Ingrid M., Limper, Maarten, Verdijk, Robert M., Donker, Marjolein L., de Jonge, Nick A., van Noesel, Carel J. M., Hebeda, Konnie M., Tonino, Sanne H., van Laar, Jan A. M., and van Halteren, Astrid G. S.

Published
2024
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3. Cryoglobulinemic Vasculitis in Disguise: Cryofibrinogenemia as Variant of Monoclonal Gammopathy of Renal Significance

Author

Circulatory Health, Pathologie Pathologen staf, MS Nefrologie, MS Hematologie, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, Gant, Christina M, Koelman, Carin A, Nguyen , Tri Q, Abrahams, Alferso C, Wetzels, Jack F M, Duineveld, Caroline, Jak, Margot, Minnema, Monique C, Klein, Saskia K, Jacobs, Joannes F M, Bosma, Renate J, Circulatory Health, Pathologie Pathologen staf, MS Nefrologie, MS Hematologie, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, Gant, Christina M, Koelman, Carin A, Nguyen , Tri Q, Abrahams, Alferso C, Wetzels, Jack F M, Duineveld, Caroline, Jak, Margot, Minnema, Monique C, Klein, Saskia K, Jacobs, Joannes F M, and Bosma, Renate J

Published
2024

4. Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy: Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

Author

MS Hematologie, Cancer, Infection & Immunity, Spanjaart, Anne Mea, Ljungman, Per, Tridello, Gloria, Schwartz, Juana, Martinez-Cibrián, Nuria, Barba, Pere, Kwon, Mi, Lopez-Corral, Lucia, Martinez-Lopez, Joaquin, Ferra, Christelle, Di Blasi, Roberta, Ghesquieres, Hervé, Mutsaers, Pim, Calkoen, Friso, Jak, Margot, van Doesum, Jaap, Vermaat, Joost S.P., van der Poel, Marjolein, Maertens, Johan, Gambella, Massimiliano, Metafuni, Elisabetta, Ciceri, Fabio, Saccardi, Riccardo, Nicholson, Emma, Tholouli, Eleni, Matthew, Collin, Potter, Victoria, Bloor, Adrian, Besley, Caroline, Roddie, Claire, Wilson, Keith, Nagler, Arnon, Campos, Antonio, Petersen, Soeren Lykke, Folber, Frantisek, Bader, Peter, Finke, Jurgen, Kroger, Nicolaus, Knelange, Nina, de La Camara, Rafael, Kersten, Marie José, Mielke, Stephan, MS Hematologie, Cancer, Infection & Immunity, Spanjaart, Anne Mea, Ljungman, Per, Tridello, Gloria, Schwartz, Juana, Martinez-Cibrián, Nuria, Barba, Pere, Kwon, Mi, Lopez-Corral, Lucia, Martinez-Lopez, Joaquin, Ferra, Christelle, Di Blasi, Roberta, Ghesquieres, Hervé, Mutsaers, Pim, Calkoen, Friso, Jak, Margot, van Doesum, Jaap, Vermaat, Joost S.P., van der Poel, Marjolein, Maertens, Johan, Gambella, Massimiliano, Metafuni, Elisabetta, Ciceri, Fabio, Saccardi, Riccardo, Nicholson, Emma, Tholouli, Eleni, Matthew, Collin, Potter, Victoria, Bloor, Adrian, Besley, Caroline, Roddie, Claire, Wilson, Keith, Nagler, Arnon, Campos, Antonio, Petersen, Soeren Lykke, Folber, Frantisek, Bader, Peter, Finke, Jurgen, Kroger, Nicolaus, Knelange, Nina, de La Camara, Rafael, Kersten, Marie José, and Mielke, Stephan

Published
2024

5. Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy:Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

Author

Spanjaart, Anne Mea, Ljungman, Per, Tridello, Gloria, Schwartz, Juana, Martinez-Cibrián, Nuria, Barba, Pere, Kwon, Mi, Lopez-Corral, Lucia, Martinez-Lopez, Joaquin, Ferra, Christelle, Di Blasi, Roberta, Ghesquieres, Hervé, Mutsaers, Pim, Calkoen, Friso, Jak, Margot, van Doesum, Jaap, Vermaat, Joost S.P., van der Poel, Marjolein, Maertens, Johan, Gambella, Massimiliano, Metafuni, Elisabetta, Ciceri, Fabio, Saccardi, Riccardo, Nicholson, Emma, Tholouli, Eleni, Matthew, Collin, Potter, Victoria, Bloor, Adrian, Besley, Caroline, Roddie, Claire, Wilson, Keith, Nagler, Arnon, Campos, Antonio, Petersen, Soeren Lykke, Folber, Frantisek, Bader, Peter, Finke, Jurgen, Kroger, Nicolaus, Knelange, Nina, de La Camara, Rafael, Kersten, Marie José, Mielke, Stephan, Spanjaart, Anne Mea, Ljungman, Per, Tridello, Gloria, Schwartz, Juana, Martinez-Cibrián, Nuria, Barba, Pere, Kwon, Mi, Lopez-Corral, Lucia, Martinez-Lopez, Joaquin, Ferra, Christelle, Di Blasi, Roberta, Ghesquieres, Hervé, Mutsaers, Pim, Calkoen, Friso, Jak, Margot, van Doesum, Jaap, Vermaat, Joost S.P., van der Poel, Marjolein, Maertens, Johan, Gambella, Massimiliano, Metafuni, Elisabetta, Ciceri, Fabio, Saccardi, Riccardo, Nicholson, Emma, Tholouli, Eleni, Matthew, Collin, Potter, Victoria, Bloor, Adrian, Besley, Caroline, Roddie, Claire, Wilson, Keith, Nagler, Arnon, Campos, Antonio, Petersen, Soeren Lykke, Folber, Frantisek, Bader, Peter, Finke, Jurgen, Kroger, Nicolaus, Knelange, Nina, de La Camara, Rafael, Kersten, Marie José, and Mielke, Stephan

Abstract

COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2–78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020–2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed.

Published
2024

6. Identifying clinical response to daratumumab therapy in relapsed/refractory multiple myeloma using a patient-derived in vitro model

Author

MS Hematologie, Infection & Immunity, Cancer, CTI Peperzak, Regenerative Medicine and Stem Cells, van Nieuwenhuijzen, Niels, Cuenca, Marta, Abbink, Leonie, Jak, Margot, Peperzak, Victor, Minnema, Monique C, MS Hematologie, Infection & Immunity, Cancer, CTI Peperzak, Regenerative Medicine and Stem Cells, van Nieuwenhuijzen, Niels, Cuenca, Marta, Abbink, Leonie, Jak, Margot, Peperzak, Victor, and Minnema, Monique C

Published
2024

7. Novel therapeutic approach in haematological malignancies: Combining histone deacetylase inhibitors with EZH2 targeting agents

Author

Schoenaker, Jente, Jak, Margot (Thesis Advisor), Schoenaker, Jente, and Jak, Margot (Thesis Advisor)

Abstract

Haematological malignancies are a clinically challenging and heterogeneous cluster of diseases that arise from hematopoietic cells with clonal proliferation. Recently, the synergistic sensitivity of haematological malignancies to a combination epigenetic therapy that includes targeting enhancer of Zeste homolog 2 (EZH2) through the drugs Tazemetostat and MS1943 and histone deacetylases (HDACs) through the drug Romidepsin was shown in peripheral T-cell lymphoma (PTCL) cell lines. However, it remains unclear whether this effect is universal for the HDAC inhibitors Belinostat, Panobinostat, and Vorinostat and a broad spectrum of haemato-oncological cell lines. Also, it remains unclear whether these drugs cause cell death through ferroptosis, necroptosis, or apoptosis. Through examining the effects of (a combination of) these drugs on cell viability, reactive oxygen species (ROS) formation, lipid peroxidation, and levels of the ferroptosis marker Acyl-CoA synthetase long-chain family member 4 (ACSL4) we will try to answer these questions. In line with previous research, synergy was found in the amount of cell death caused by the HDAC inhibitors Belinostat, Panobinostat, and Vorinostat in combination with the EZH2 targeting drugs MS1943 and Tazemetostat. Also, the HDAC inhibitor Romidepsin caused an increase in ROS formation and lipid peroxidation when combined with MS1943 and Tazemetostat. Furthermore, ferroptosis was found to be the most influential in causing cell death when combining Romidepsin with MS1943 or Tazemetostat. Our findings indicate that a broad spectrum of HDAC inhibitors have a synergistic effect with EZH2 targeting drugs in causing cell death and the main mechanism of cell death is ferroptosis.

Published
2024

9. Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities

Author

de Boer, Janneke W., primary, Keijzer, Kylie, additional, Pennings, Elise R. A., additional, van Doesum, Jaap A., additional, Spanjaart, Anne M., additional, Jak, Margot, additional, Mutsaers, Pim G. N. J., additional, van Dorp, Suzanne, additional, Vermaat, Joost S. P., additional, van der Poel, Marjolein W. M., additional, van Dijk, Lisanne V., additional, Kersten, Marie José, additional, Niezink, Anne G. H., additional, and van Meerten, Tom, additional

Published
2023
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10. Inflammatory reactions mimic residual or recurrent lymphoma on [18F]FDG-PET/CT after CD19-directed CAR T-cell therapy

Author

de Boer, Janneke W., primary, Pennings, Elise R. A., additional, Kleinjan, Ankie, additional, van Doesum, Jaap A., additional, Spanjaart, Anne M., additional, Mutsaers, Pim G. N. J., additional, Jak, Margot, additional, van der Poel, Marjolein W. M., additional, Kuipers, Maria T., additional, Adam, Judit A., additional, Diepstra, Arjan, additional, Koens, Lianne, additional, van Dorp, Suzanne, additional, Vermaat, Joost S. P., additional, Niezink, Anne G. H., additional, Kersten, Marie José, additional, and van Meerten, Tom, additional

Published
2023
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11. Cryoglobulinemic Vasculitis in Disguise: Cryofibrinogenemia as Variant of Monoclonal Gammopathy of Renal Significance

Author

Gant, Christina M., primary, Koelman, Carin A., additional, Nguyen TQ, Tri Q., additional, Abrahams, Alferso C., additional, Wetzels, Jack F.M., additional, Duineveld, Caroline, additional, Jak, Margot, additional, Minnema, Monique C., additional, Klein, Saskia K., additional, Jacobs, Joannes F.M., additional, and Bosma, Renate J., additional

Published
2023
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12. The Dutch CAR-T Tumorboard Experience: Population-Based Real-World Data on Patients with Relapsed or Refractory Large B-Cell Lymphoma Referred for CD19-Directed CAR T-Cell Therapy in The Netherlands

Author

Spanjaart, Anne M., primary, Pennings, Elise R. A., additional, Mutsaers, Pim G. N. J., additional, van Dorp, Suzanne, additional, Jak, Margot, additional, van Doesum, Jaap A., additional, de Boer, Janneke W., additional, Niezink, Anne G. H., additional, Kos, Milan, additional, Vermaat, Joost S. P., additional, Sijs-Szabo, Aniko, additional, van der Poel, Marjolein W. M., additional, Nijhof, Inger S., additional, Kuipers, Maria T., additional, Chamuleau, Martine E. D., additional, Lugtenburg, Pieternella J., additional, Doorduijn, Jeanette K., additional, Serroukh, Yasmina I. M., additional, Minnema, Monique C., additional, van Meerten, Tom, additional, and Kersten, Marie José, additional

Published
2023
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13. P1128: EVALUATION OF STANDARD OF CARE IN SECOND-LINE FOR PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA IN THE PRE-CAR-T ERA: A DUTCH POPULATION-BASED STUDY

Author

Pennings, Elise R.A., primary, Durmaz, Müjde, additional, Visser, Otto, additional, Posthuma, Eduardus F.M., additional, Issa, Djamila E., additional, Chamuleau, Martine E.D., additional, Spanjaart, Anne M., additional, van Meerten, Tom, additional, Mutsaers, Pim G.N.J., additional, Jak, Margot, additional, van Dorp, Suzanne, additional, Vermaat, Joost S.P., additional, van der Poel, Marjolein W.M., additional, Kuipers, Maria T., additional, Thielen, Frederick W., additional, Uyl-de Groot, Carin A., additional, Lugtenburg, Pieternella J., additional, José Kersten, Marie, additional, and Dinmohamed, Avinash G., additional

Published
2023
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15. Development of a Core Set of Patient- and Caregiver-Reported Signs and Symptoms to Facilitate Early Recognition of Acute Chimeric Antigen Receptor T-Cell Therapy Toxicities

Author

Spanjaart, Anne M., primary, Pennings, Elise R.A., additional, Kos, Milan, additional, Mutsaers, Pim G.N.J., additional, Lugtenburg, Pieternella J., additional, van Meerten, Tom, additional, van Doesum, Jaap A., additional, Minnema, Monique C., additional, Jak, Margot, additional, van Dorp, Suzanne, additional, Vermaat, Joost S.P., additional, van der Poel, Marjolein W.M., additional, van Oijen, Martijn G.H., additional, Kuipers, Maria T., additional, Nijhof, Inger S., additional, and Kersten, Marie José, additional

Published
2023
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16. Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities

Author

de Boer, Janneke W., Keijzer, Kylie, Pennings, Elise R.A., van Doesum, Jaap A., Spanjaart, Anne M., Jak, Margot, Mutsaers, Pim G.N.J., van Dorp, Suzanne, Vermaat, Joost S.P., van der Poel, Marjolein W.M., van Dijk, Lisanne V., Kersten, Marie José, Niezink, Anne G.H., van Meerten, Tom, de Boer, Janneke W., Keijzer, Kylie, Pennings, Elise R.A., van Doesum, Jaap A., Spanjaart, Anne M., Jak, Margot, Mutsaers, Pim G.N.J., van Dorp, Suzanne, Vermaat, Joost S.P., van der Poel, Marjolein W.M., van Dijk, Lisanne V., Kersten, Marie José, Niezink, Anne G.H., and van Meerten, Tom

Abstract

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (both p = 0.04), and the EASIX approached statistical significance at infusion (p = 0.05). However, the predictive performance was moderate, with area under the curves of 0.61–0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment.

Published
2023

17. Inflammatory reactions mimic residual or recurrent lymphoma on [18F]FDG-PET/CT after CD19-directed CAR T-cell therapy

Author

de Boer, Janneke W., Pennings, Elise R.A., Kleinjan, Ankie, van Doesum, Jaap A., Spanjaart, Anne M., Mutsaers, Pim G.N.J., Jak, Margot, van der Poel, Marjolein W.M., Kuipers, Maria T., Adam, Judit A., Diepstra, Arjan, Koens, Lianne, van Dorp, Suzanne, Vermaat, Joost S.P., Niezink, Anne G.H., Kersten, Marie José, van Meerten, Tom, de Boer, Janneke W., Pennings, Elise R.A., Kleinjan, Ankie, van Doesum, Jaap A., Spanjaart, Anne M., Mutsaers, Pim G.N.J., Jak, Margot, van der Poel, Marjolein W.M., Kuipers, Maria T., Adam, Judit A., Diepstra, Arjan, Koens, Lianne, van Dorp, Suzanne, Vermaat, Joost S.P., Niezink, Anne G.H., Kersten, Marie José, and van Meerten, Tom

Published
2023

18. The Dutch CAR-T Tumorboard Experience:Population-Based Real-World Data on Patients with Relapsed or Refractory Large B-Cell Lymphoma Referred for CD19-Directed CAR T-Cell Therapy in The Netherlands

Author

Spanjaart, Anne M., Pennings, Elise R.A., Mutsaers, Pim G.N.J., van Dorp, Suzanne, Jak, Margot, van Doesum, Jaap A., de Boer, Janneke W., Niezink, Anne G.H., Kos, Milan, Vermaat, Joost S.P., Sijs-Szabo, Aniko, van der Poel, Marjolein W.M., Nijhof, Inger S., Kuipers, Maria T., Chamuleau, Martine E.D., Lugtenburg, Pieternella J., Doorduijn, Jeanette K., Serroukh, Yasmina I.M., Minnema, Monique C., van Meerten, Tom, Kersten, Marie José, Spanjaart, Anne M., Pennings, Elise R.A., Mutsaers, Pim G.N.J., van Dorp, Suzanne, Jak, Margot, van Doesum, Jaap A., de Boer, Janneke W., Niezink, Anne G.H., Kos, Milan, Vermaat, Joost S.P., Sijs-Szabo, Aniko, van der Poel, Marjolein W.M., Nijhof, Inger S., Kuipers, Maria T., Chamuleau, Martine E.D., Lugtenburg, Pieternella J., Doorduijn, Jeanette K., Serroukh, Yasmina I.M., Minnema, Monique C., van Meerten, Tom, and Kersten, Marie José

Abstract

The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020–May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need.

Published
2023

19. Development of a Core Set of Patient- and Caregiver-Reported Signs and Symptoms to Facilitate Early Recognition of Acute Chimeric Antigen Receptor T-Cell Therapy Toxicities

Author

Spanjaart, Anne M., Pennings, Elise R.A., Kos, Milan, Mutsaers, Pim G.N.J., Lugtenburg, Pieternella J., Van Meerten, Tom, Van Doesum, Jaap A., Minnema, Monique C., Jak, Margot, Van Dorp, Suzanne, Vermaat, Joost S.P., Van Der Poel, Marjolein W.M., Van Oijen, Martijn G.H., Kuipers, Maria T., Nijhof, Inger S., Kersten, Marie José, Spanjaart, Anne M., Pennings, Elise R.A., Kos, Milan, Mutsaers, Pim G.N.J., Lugtenburg, Pieternella J., Van Meerten, Tom, Van Doesum, Jaap A., Minnema, Monique C., Jak, Margot, Van Dorp, Suzanne, Vermaat, Joost S.P., Van Der Poel, Marjolein W.M., Van Oijen, Martijn G.H., Kuipers, Maria T., Nijhof, Inger S., and Kersten, Marie José

Abstract

PURPOSE:Prompt recognition of acute chimeric antigen receptor T (CAR T)-cell-mediated toxicities is crucial because adequate and timely management can prevent or reverse potential life-threatening complications. In the outpatient setting, patients and informal caregivers have to recognize and report signs and symptoms marking these acute toxicities. This study provides a core set of patient- and caregiver-reported signs and symptoms (outcomes, P/CROs) and definitions of red flags warranting immediate action to include in a daily checklist for support at home, with the goal to make outpatient post-CAR T-cell care safer, optimize patient and caregiver support, and thereby facilitating an early discharge/hospital visit reduction strategy.METHODS:We performed a systematic review of phase II/III trials of US Food and Drug Administration-approved CAR T-cell products and selected all common and severe adverse events that could be translated into a P/CRO for inclusion in a two-round modified Delphi procedure. Eleven CAR T-cell-dedicated hematologists from the Dutch CAR T-cell tumorboard representing all treating centers selected P/CROs for inclusion in the core set and defined red flags. The final core set was evaluated with patients and caregivers.RESULTS:From nine clinical trials, 457 adverse events were identified of which 42 could be used as P/CRO. The final core set contains 28 items, including five signs for measurement via wearables and two signs for caregiver-performed assessments.CONCLUSION:This study provides a core set of P/CROs that can serve as a framework for (eHealth) tools that aim to enable patients and caregivers to more effectively recognize and report signs and symptoms of acute toxicities after CAR T-cell therapy, which will enhance safe outpatient treatment monitoring.

Published
2023

20. Inflammatory reactions mimic residual or recurrent lymphoma on [18F]FDG-PET/CT after CD19-directed CAR T-cell therapy

Author

MS Hematologie, Cancer, Infection & Immunity, de Boer, Janneke W., Pennings, Elise R.A., Kleinjan, Ankie, van Doesum, Jaap A., Spanjaart, Anne M., Mutsaers, Pim G.N.J., Jak, Margot, van der Poel, Marjolein W.M., Kuipers, Maria T., Adam, Judit A., Diepstra, Arjan, Koens, Lianne, van Dorp, Suzanne, Vermaat, Joost S.P., Niezink, Anne G.H., Kersten, Marie José, van Meerten, Tom, MS Hematologie, Cancer, Infection & Immunity, de Boer, Janneke W., Pennings, Elise R.A., Kleinjan, Ankie, van Doesum, Jaap A., Spanjaart, Anne M., Mutsaers, Pim G.N.J., Jak, Margot, van der Poel, Marjolein W.M., Kuipers, Maria T., Adam, Judit A., Diepstra, Arjan, Koens, Lianne, van Dorp, Suzanne, Vermaat, Joost S.P., Niezink, Anne G.H., Kersten, Marie José, and van Meerten, Tom

Published
2023

21. Development of a Core Set of Patient- and Caregiver-Reported Signs and Symptoms to Facilitate Early Recognition of Acute Chimeric Antigen Receptor T-Cell Therapy Toxicities

Author

MS Hematologie, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, Externen Med. Onco, Spanjaart, Anne M, Pennings, Elise R A, Kos, Milan, Mutsaers, Pim G N J, Lugtenburg, Pieternella J, van Meerten, Tom, van Doesum, Jaap A, Minnema, Monique C, Jak, Margot, van Dorp, Suzanne, Vermaat, Joost S P, van der Poel, Marjolein W M, van Oijen, Martijn G H, Kuipers, Maria T, Nijhof, Inger S, Kersten, Marie José, MS Hematologie, Cancer, Infection & Immunity, Regenerative Medicine and Stem Cells, Externen Med. Onco, Spanjaart, Anne M, Pennings, Elise R A, Kos, Milan, Mutsaers, Pim G N J, Lugtenburg, Pieternella J, van Meerten, Tom, van Doesum, Jaap A, Minnema, Monique C, Jak, Margot, van Dorp, Suzanne, Vermaat, Joost S P, van der Poel, Marjolein W M, van Oijen, Martijn G H, Kuipers, Maria T, Nijhof, Inger S, and Kersten, Marie José

Published
2023

29. Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients

Author

CDL KAM KC, MS Hematologie, Regenerative Medicine and Stem Cells, Cancer, Infection & Immunity, Oostvogels, Rimke, Jak, Margot, Raymakers, Reinier, Mous, Rogier, Minnema, Monique C., CDL KAM KC, MS Hematologie, Regenerative Medicine and Stem Cells, Cancer, Infection & Immunity, Oostvogels, Rimke, Jak, Margot, Raymakers, Reinier, Mous, Rogier, and Minnema, Monique C.

Published
2018

33. IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of chronic lymphocytic leukemia cells (P2167)

Author

Pascutti, Maria Fernanda, primary, Jak, Margot, additional, Tromp, Jacqueline, additional, van Bochove, Gregor, additional, Derks, Ingrid, additional, Luijks, Dieuwertje, additional, Pals, Steven, additional, van Lier, Rene, additional, Kater, Arnon, additional, van Oers, Marinus, additional, and Eldering, Eric, additional

Published
2013
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38. Attacking Oncogene Addiction in B-CLL: Seliciclib First Engages the Mcl-1/Noxa Axis, after Which Gradual Exhaustion of Bcl-2 Protection Leads to Bax Activation.

Author

Hallaert, Delfine Y.H., primary, Spijker, Rene, additional, Jak, Margot, additional, Jaspers, Annelieke, additional, Derks, Ingrid A.M., additional, Alves, Nuno L., additional, de Boer, Jan Paul, additional, de Jong, Daphne, additional, Green, Simon R., additional, van Lier, Rene A.W., additional, van Oers, Marinus H.J., additional, and Eldering, Eric, additional

Published
2006
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41. Enhanced formation and survival of CD4+ CD25hi Foxp3+ T-cells in chronic lymphocytic leukemia.

Author

Jak, Margot, Mous, Rogier, Remmerswaal, Ester B. M., Spijker, René, Jaspers, Annelieke, Yagüe, Adriana, Eldering, Eric, Van Lier, René A. W., and Van Oers, Marinus H. J.

Subjects
*CHRONIC lymphocytic leukemia, *T cells, *LIGANDS (Biochemistry), *APOPTOSIS, *LYMPH nodes
Abstract

Recently, it has been described that patients with chronic lymphocytic leukemia (CLL) have increased numbers of regulatory T (Treg) cells. In the present study, we analysed the mechanism behind Treg cells expansion in CLL. Neither analysis of the T-cell receptor repertoire nor CD45 isoform expression of Treg cells from patients with CLL provided evidence for chronic (tumor) antigenic stimulation as a possible cause for Treg cells expansion in CLL. We found evidence however for increased formation of Treg cells via CD70 costimulation, because we observed that CD40 ligand activated CLL cells (which might be considered a model of lymph node CLL cells) strongly induced CD70-dependent formation of Treg cells. Reverse transcription-multiplex ligation-dependent probe amplification assay expression analysis of 34 apoptosis-regulating genes showed that in comparison with other CD4+ T-cells, Treg cells from both healthy individuals (HD) and patients with CLL had a high expression of pro-apoptotic Noxa and a low expression of anti-apoptotic Bcl-2. Strikingly, Bcl-2 levels of Treg cells in patients with CLL were significantly higher than in HD. Finally, the different apoptotic profile resulted in differences at the functional level, because Treg cells from patients with CLL were more resistant to drug-induced apoptosis than Treg cells from HD. In conclusion, Treg cells in CLL may accumulate both by increased formation, facilitated by CD27-CD70 interaction in the lymph node proliferation centres, and decreased sensitivity to apoptosis because of a shifted Noxa-Bcl-2 balance. [ABSTRACT FROM AUTHOR]

Published
2009
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