30 results on '"Duetz, C."'
Search Results
2. Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes:the HOVON89 trial
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van de Loosdrecht, A. A., Cremers, E. M.P., Alhan, C., Duetz, C., in ’t Hout, F. E.M., Visser-Wisselaar, H. A., Chitu, D. A., Verbrugge, A., Cunha, S. M., Ossenkoppele, G. J., Janssen, J. J.W.M., Klein, S. K., Vellenga, E., Huls, G. A., Muus, P., Langemeijer, S. M.C., de Greef, G. E., te Boekhorst, P. A.W., Raaijmakers, M. H.G., van Marwijk Kooy, M., Legdeur, M. C., Wegman, J. J., Deenik, W., de Weerdt, O., van Maanen-Lamme, T. M., Jobse, P., van Kampen, R. J.W., Beeker, A., Wijermans, P. W., Biemond, B. J., Tanis, B. C., van Esser, J. W.J., Schaar, C. G., Noordzij-Nooteboom, H. S., Jacobs, E. M.G., de Graaf, A. O., Jongen-Lavrencic, M., Stevens-Kroef, M. J.P.L., Westers, T. M., Jansen, J. H., van de Loosdrecht, A. A., Cremers, E. M.P., Alhan, C., Duetz, C., in ’t Hout, F. E.M., Visser-Wisselaar, H. A., Chitu, D. A., Verbrugge, A., Cunha, S. M., Ossenkoppele, G. J., Janssen, J. J.W.M., Klein, S. K., Vellenga, E., Huls, G. A., Muus, P., Langemeijer, S. M.C., de Greef, G. E., te Boekhorst, P. A.W., Raaijmakers, M. H.G., van Marwijk Kooy, M., Legdeur, M. C., Wegman, J. J., Deenik, W., de Weerdt, O., van Maanen-Lamme, T. M., Jobse, P., van Kampen, R. J.W., Beeker, A., Wijermans, P. W., Biemond, B. J., Tanis, B. C., van Esser, J. W.J., Schaar, C. G., Noordzij-Nooteboom, H. S., Jacobs, E. M.G., de Graaf, A. O., Jongen-Lavrencic, M., Stevens-Kroef, M. J.P.L., Westers, T. M., and Jansen, J. H.
- Abstract
A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).
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- 2024
3. Merging and imputation of flow cytometry data: A critical assessment
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Mocking, T. R., primary, Duetz, C., additional, van Kuijk, B. J., additional, Westers, T. M., additional, Cloos, J., additional, and Bachas, C., additional
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- 2023
- Full Text
- View/download PDF
4. Merging and imputation of flow cytometry data:A critical assessment
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Mocking, T R, Duetz, C, van Kuijk, B J, Westers, T M, Cloos, J, and Bachas, C
- Abstract
Although most modern techniques and analysis methods in multiparameter flow cytometry (MFC) allow for increased dimensionality for the characterization and quantification of cell populations, most MFC applications depend on flow cytometers measuring relatively small (
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- 2023
5. Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European LeukemiaNet International MDS-Flow Cytometry Working Group.
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Loosdrecht, A.A. van de, Kern, W., Porwit, A., Valent, P., Kordasti, S., Cremers, E., Alhan, C., Duetz, C., Dunlop, A., Hobo, W.A., Preijers, F.W., Wagner-Ballon, O., Chapuis, N., Fontenay, M., Bettelheim, P., Eidenschink-Brodersen, L., Font, P., Johansson, U., Loken, M.R., Marvelde, J.G. Te, Matarraz, S., Ogata, K., Oelschlaegel, U., Orfao, A., Psarra, K., Subirá, D., Wells, D.A., Béné, M.C., Porta, M.G. Della, Burbury, K., Bellos, F., Velden, V.H. van der, Westers, Theresia M., Saft, L., Ireland, R., Loosdrecht, A.A. van de, Kern, W., Porwit, A., Valent, P., Kordasti, S., Cremers, E., Alhan, C., Duetz, C., Dunlop, A., Hobo, W.A., Preijers, F.W., Wagner-Ballon, O., Chapuis, N., Fontenay, M., Bettelheim, P., Eidenschink-Brodersen, L., Font, P., Johansson, U., Loken, M.R., Marvelde, J.G. Te, Matarraz, S., Ogata, K., Oelschlaegel, U., Orfao, A., Psarra, K., Subirá, D., Wells, D.A., Béné, M.C., Porta, M.G. Della, Burbury, K., Bellos, F., Velden, V.H. van der, Westers, Theresia M., Saft, L., and Ireland, R.
- Abstract
01 januari 2023, Item does not contain fulltext, This article discusses the rationale for inclusion of flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias of uncertain origin and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group (ELN iMDS Flow WG). The WHO 2016 classification recognizes that FCM contributes to the diagnosis of MDS and may be useful for prognostication, prediction, and evaluation of response to therapy and follow-up of MDS patients.
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- 2023
6. Flow cytometric analysis of myelodysplasia: Pre-analytical and technical issues-Recommendations from the European LeukemiaNet.
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Velden, V.H. van der, Preijers, F.W., Johansson, U., Westers, Theresia M., Dunlop, A., Porwit, A., Béné, M.C., Valent, P., Marvelde, J. Te, Wagner-Ballon, O., Oelschlaegel, U., Saft, L., Kordasti, S., Ireland, R., Cremers, E., Alhan, C., Duetz, C., Hobo, W.A., Chapuis, N., Fontenay, M., Bettelheim, P., Eidenshink-Brodersen, L., Font, P., Loken, M.R., Matarraz, S., Ogata, K., Orfao, A., Psarra, K., Subirá, D., Wells, D.A., Porta, M.G. Della, Burbury, K., Bellos, F., Weiß, E., Kern, W., Loosdrecht, A. van de, Velden, V.H. van der, Preijers, F.W., Johansson, U., Westers, Theresia M., Dunlop, A., Porwit, A., Béné, M.C., Valent, P., Marvelde, J. Te, Wagner-Ballon, O., Oelschlaegel, U., Saft, L., Kordasti, S., Ireland, R., Cremers, E., Alhan, C., Duetz, C., Hobo, W.A., Chapuis, N., Fontenay, M., Bettelheim, P., Eidenshink-Brodersen, L., Font, P., Loken, M.R., Matarraz, S., Ogata, K., Orfao, A., Psarra, K., Subirá, D., Wells, D.A., Porta, M.G. Della, Burbury, K., Bellos, F., Weiß, E., Kern, W., and Loosdrecht, A. van de
- Abstract
01 januari 2023, Item does not contain fulltext, BACKGROUND: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. METHODS: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. RESULTS: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. CONCLUSIONS: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice.
- Published
- 2023
7. Multiparameter flow cytometry in the evaluation of myelodysplasia: Analytical issues: Recommendations from the European LeukemiaNet/International Myelodysplastic Syndrome Flow Cytometry Working Group.
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Porwit, A., Béné, M.C., Duetz, C., Matarraz, S., Oelschlaegel, U., Westers, Theresia M., Wagner-Ballon, O., Kordasti, S., Valent, P., Preijers, F.W., Alhan, C., Bellos, F., Bettelheim, P., Burbury, K., Chapuis, N., Cremers, E., Porta, M.G. Della, Dunlop, A., Eidenschink-Brodersen, L., Font, P., Fontenay, M., Hobo, W., Ireland, R., Johansson, U., Loken, M.R., Ogata, K., Orfao, A., Psarra, K., Saft, L., Subira, D., Marvelde, J. Te, Wells, D.A., Velden, V.H. van der, Kern, W., Loosdrecht, A.A. van de, Porwit, A., Béné, M.C., Duetz, C., Matarraz, S., Oelschlaegel, U., Westers, Theresia M., Wagner-Ballon, O., Kordasti, S., Valent, P., Preijers, F.W., Alhan, C., Bellos, F., Bettelheim, P., Burbury, K., Chapuis, N., Cremers, E., Porta, M.G. Della, Dunlop, A., Eidenschink-Brodersen, L., Font, P., Fontenay, M., Hobo, W., Ireland, R., Johansson, U., Loken, M.R., Ogata, K., Orfao, A., Psarra, K., Saft, L., Subira, D., Marvelde, J. Te, Wells, D.A., Velden, V.H. van der, Kern, W., and Loosdrecht, A.A. van de
- Abstract
01 januari 2023, Item does not contain fulltext, Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic syndrome (MDS). MFC can also be applied in the follow-up of MDS patients undergoing treatment. This document summarizes recommendations from the International/European Leukemia Net Working Group for Flow Cytometry in Myelodysplastic Syndromes (ELN iMDS Flow) on the analytical issues in MFC for the diagnostic work-up of MDS. Recommendations for the analysis of several BM cell subsets such as myeloid precursors, maturing granulocytic and monocytic components and erythropoiesis are given. A core set of 17 markers identified as independently related to a cytomorphologic diagnosis of myelodysplasia is suggested as mandatory for MFC evaluation of BM in a patient with cytopenia. A myeloid precursor cell (CD34(+) CD19(-) ) count >3% should be considered immunophenotypically indicative of myelodysplasia. However, MFC results should always be evaluated as part of an integrated hematopathology work-up. Looking forward, several machine-learning-based analytical tools of interest should be applied in parallel to conventional analytical methods to investigate their usefulness in integrated diagnostics, risk stratification, and potentially even in the evaluation of response to therapy, based on MFC data. In addition, compiling large uniform datasets is desirable, as most of the machine-learning-based methods tend to perform better with larger numbers of investigated samples, especially in such a heterogeneous disease as MDS.
- Published
- 2023
8. P1254: RESPONSE TO DA-EPOCH-R IN PATIENTS WITH HIGH GRADE B CELL LYMPHOMA IS ASSOCIATED WITH A REDUCTION OF PD1 POSITIVE EXHAUSTED CD8 T CELLS
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de Jonge, V., primary, Duetz, C., additional, Bruins, W., additional, van Werkhoven, E., additional, Nijland, M., additional, de Heer, K., additional, van der Poel, M., additional, Sandberg, Y., additional, Klerk, C., additional, de Jong, D., additional, Zijlstra, J., additional, Kersten, M. J., additional, Mutis, T., additional, and Chamuleau, M., additional
- Published
- 2022
- Full Text
- View/download PDF
9. Distinct bone marrow immunophenotypic features define the splicing factor 3B subunit 1 (SF3B1)-mutant myelodysplastic syndromes subtype
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Duetz, C., Westers, T.M., Hout, F.E.M. In 't, Cremers, E.M., Alhan, C., Venniker-Punt, B., Visser-Wisselaar, H.A., Chitu, Dana A., Graaf, A.O. de, Smit, L., Jansen, J.H., Loosdrecht, A.A. van de, Duetz, C., Westers, T.M., Hout, F.E.M. In 't, Cremers, E.M., Alhan, C., Venniker-Punt, B., Visser-Wisselaar, H.A., Chitu, Dana A., Graaf, A.O. de, Smit, L., Jansen, J.H., and Loosdrecht, A.A. van de
- Abstract
Contains fulltext : 235747.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
10. Flow cytometric analysis of myelodysplasia: Pre-analytical and technical issues-Recommendations from the European LeukemiaNet
- Author
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van der Velden, VHJ, Preijers, F, Johansson, U, Westers, TM, Dunlop, A, Porwit, A, Bene, MC, Valent, P, te Marvelde, J, Wagner-Ballon, O, Oelschlaegel, U, Saft, L, Kordasti, S, Ireland, R, Cremers, E, Alhan, C, Duetz, C, Hobo, W, Chapuis, N, Fontenay, M, Bettelheim, P, Eidenshink-Brodersen, L, Font, P, Loken, MR, Matarraz, S, Ogata, K, Orfao, A, Psarra, K, Subira, D, Wells, DA, Della Porta, MG, Burbury, K, Bellos, F, Weiss, E, Kern, W, van de Loosdrecht, A, van der Velden, VHJ, Preijers, F, Johansson, U, Westers, TM, Dunlop, A, Porwit, A, Bene, MC, Valent, P, te Marvelde, J, Wagner-Ballon, O, Oelschlaegel, U, Saft, L, Kordasti, S, Ireland, R, Cremers, E, Alhan, C, Duetz, C, Hobo, W, Chapuis, N, Fontenay, M, Bettelheim, P, Eidenshink-Brodersen, L, Font, P, Loken, MR, Matarraz, S, Ogata, K, Orfao, A, Psarra, K, Subira, D, Wells, DA, Della Porta, MG, Burbury, K, Bellos, F, Weiss, E, Kern, W, and van de Loosdrecht, A
- Abstract
BACKGROUND: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. METHODS: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. RESULTS: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. CONCLUSIONS: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice.
- Published
- 2021
11. Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European LeukemiaNet International MDS-Flow Cytometry Working Group
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Loosdrecht, AA, Kern, W, Porwit, A, Valent, P, Kordasti, S, Cremers, E, Alhan, C, Duetz, C, Dunlop, A, Hobo, W, Preijers, F, Wagner-Ballon, O, Chapuis, N, Fontenay, M, Bettelheim, P, Eidenschink-Brodersen, L, Font, P, Johansson, U, Loken, MR, Marvelde, JG, Matarraz, S, Ogata, K, Oelschlaegel, U, Orfao, A, Psarra, K, Subira, D, Wells, DA, Bene, MC, Della Porta, MG, Burbury, K, Bellos, F, van der Velden, VHJ, Westers, TM, Saft, L, Ireland, R, Loosdrecht, AA, Kern, W, Porwit, A, Valent, P, Kordasti, S, Cremers, E, Alhan, C, Duetz, C, Dunlop, A, Hobo, W, Preijers, F, Wagner-Ballon, O, Chapuis, N, Fontenay, M, Bettelheim, P, Eidenschink-Brodersen, L, Font, P, Johansson, U, Loken, MR, Marvelde, JG, Matarraz, S, Ogata, K, Oelschlaegel, U, Orfao, A, Psarra, K, Subira, D, Wells, DA, Bene, MC, Della Porta, MG, Burbury, K, Bellos, F, van der Velden, VHJ, Westers, TM, Saft, L, and Ireland, R
- Abstract
This article discusses the rationale for inclusion of flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias of uncertain origin and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group (ELN iMDS Flow WG). The WHO 2016 classification recognizes that FCM contributes to the diagnosis of MDS and may be useful for prognostication, prediction, and evaluation of response to therapy and follow-up of MDS patients.
- Published
- 2021
12. Macroscopic hematuria as presenting symptom of celiac disease
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Duetz, C., Houtenbos, I., Camiel de Roij van Zuijdewijn, Clinical Haematology, Nephrology, and ACS - Diabetes & metabolism
- Subjects
Diagnosis, Differential ,Male ,Vitamin K Deficiency/complications ,Treatment Outcome ,Hematuria/etiology ,Humans ,Middle Aged ,Celiac Disease/complications - Abstract
A 47-year old man was admitted for macroscopic hematuria and spontaneous hematomas. Laboratory results showed a prolonged partial thromboplastin time (PTT), a prolonged activated partial thromboplastin time (APTT) and a severe vitamin K deficiency. The underlying cause proved to be vitamin K malabsorption due to previously undiagnosed celiac disease, possibly provoked by oral antibiotic administration.
- Published
- 2019
13. 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
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Vera de Jonge, A., Duetz, C, Bruins, WSC, van Werkhoven, Erik, Nijland, M., van der Poel, Marjolein W. M., de Heer, K, Klerk, CPW, Sandberg, Yorick, Fijnheer, Rob, Mutsaers, Pim G.N.J., Issa, DE, Lara H Bohmer, van Kampen, Roel J.W., Visser, O, de Jong, D, Zijlstra-Baalbergen, JM, Mutis, T, Chamuleau, MED, Hematology laboratory, CCA - Cancer biology and immunology, AII - Cancer immunology, Pathology, CCA - Imaging and biomarkers, AII - Infectious diseases, Hematology, and CCA - Cancer Treatment and quality of life
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
Introduction Treatment of patients with high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) with intensified immune-chemotherapy DA-EPOCH-R results in a 48-month event-free survival of 71.0% [Dunleavy, Lancet Haematol 2018]. In the HOVON-152, we investigate the added value of immune checkpoint PD-1 inhibition for patients who achieve complete metabolic remission (CMR) after DA-EPOCH-R induction. Nonetheless, whether DA-EPOCH-R has an effect on the immune system, and - reversely - whether the composition of immune system influences DA-EPOCH-R therapy are not known. To gain more insight on these important issues, we performed longitudinal high-throughput immune profiling of patients during the DA-EPOCH-R induction phase of the HOVON-152.Methods In the HOVON-152 single arm, phase II trial (NCT03620578) HGBL-DH/TH patients received 1 cycle of R-CHOP followed by 5 cycles of DA-EPOCH-R induction treatment. Peripheral blood was sampled after one cycle of R-CHOP (enrollment), before start of the 3rd DA-EPOCH-R cycle (midterm) and after the last DA-EPOCH-R cycle (end-of-induction, EOI). Patients achieving CMR at EOI (Deauville score 1-3 after induction) were identified as responders and proceeded with nivolumab consolidation (480 mg iv every 4 weeks) for 1 year.For the profiling we selected 55 patients (32 responders and 23 non-responders, enriched for non-responders) who completed the whole study. T and NK cells were enumerated through quantitative, dual platform flow cytometry of unseparated full blood. The frequencies of NK and T cell subsets were determined in cryopreserved PBMC through multiparameter flow cytometry. The high-throughput flow cytometry data were analyzed by computational methods UMAP and FlowSOM. Non-parametric methods were used for statistical testing.Results DA-EPOCH-R had no apparent effects on the total number of NK cells. The frequency of cytotoxic CD56dim NK cells was, however, gradually decreased during DA-EPOCH-R (pMore interestingly, DA-EPOCH-R appeared to have significant impact on T cells: while total T cell frequencies and numbers showed only a temporary decrease at midterm, a progressive decrease in the CD4/CD8 ratio (p=0.016) and a progressive increase in the expression of T cell activation markers CD127 (pFurther analyses regarding the possible impact of immune system on DA-EPOCH-R outcome revealed that a (relative) abundance of non-cytotoxic CD56bright NK cells (p=0.006) and higher CD3 T cells (p=0.04) at enrollment was associated with achievement of CMR.Conclusion In conclusion, treatment of HGBL-DH/TH patients with DA-EPOCH-R results not only in the expected rituximab-mediated alterations in the NK cell compartment, but also influences the T cell compartment with a shift towards a lower CD4/CD8 ratio, more T cell activation and a reduction of PD-1 expression on CD8 T cells. Higher T cell frequencies at baseline and decreased frequencies of PD-1+ CD8 T cells at EOI were furthermore associated with achievement of CMR. Overall, these data contribute to a wider understanding of NK and T cell dynamics during DA-EPOCH-R and points to an considerable involvement of T cells in therapy outcome.DisclosuresNijland:Takeda: Research Funding; Roche: Research Funding; Genmab: Consultancy. Klerk:Roche: Other: speaker fee (ASH). Mutseaers:Glaxo Smith Kline: Consultancy; Astra Zeneca: Research Funding; BMS: Consultancy. Mutis:Janssen: Research Funding; Genmab: Research Funding; Takeda: Research Funding. Chamuleau:Genmab: Research Funding; Novartis: Honoraria; Abbvie: Honoraria; Roche: Honoraria; Gilead: Research Funding; BMS/Celgene: Honoraria, Research Funding.OffLabel Disclosure:Nivolumab as immune checkpoint inhibitor (inhibiting PD-1) in consolidation phase for the treatment of DH/TH-HGBL patientsAuthor notes*Asterisk with author names denotes non-ASH members.
14. T-Cell Characteristics Impact Response and Resistance to T-Cell-Redirecting Bispecific Antibodies in Multiple Myeloma.
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Verkleij CPM, O'Neill CA, Broekmans MEC, Frerichs KA, Bruins WSC, Duetz C, Kruyswijk S, Baglio SR, Skerget S, Montes de Oca R, Zweegman S, Verona RI, Mutis T, and van de Donk NWCJ
- Subjects
- Humans, B-Cell Maturation Antigen immunology, T-Lymphocytes, Regulatory immunology, Female, Male, T-Lymphocytes immunology, T-Lymphocytes metabolism, Middle Aged, Aged, Receptors, G-Protein-Coupled, Multiple Myeloma immunology, Multiple Myeloma drug therapy, Multiple Myeloma pathology, Antibodies, Bispecific pharmacology, Antibodies, Bispecific therapeutic use, Drug Resistance, Neoplasm immunology
- Abstract
Purpose: Bispecific antibodies (BsAb) directed against B-cell maturation antigen (teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated patients with multiple myeloma. However, mechanisms underlying primary and acquired resistance remain poorly understood., Experimental Design: The anti-multiple myeloma activity of teclistamab and talquetamab was evaluated in bone marrow (BM) samples from patients with multiple myeloma. T-cell phenotype and function were assessed in BM/peripheral blood samples obtained from patients with multiple myeloma who were treated with these BsAb., Results: In ex vivo killing assays with 41 BM samples from BsAb-naive patients with multiple myeloma, teclistamab- and talquetamab-mediated multiple myeloma lysis was strongly correlated (r = 0.73, P < 0.0001). Both BsAb exhibited poor activity in samples with high regulatory T-cell (Treg) numbers and a low T-cell/multiple myeloma cell ratio. Furthermore, comprehensive phenotyping of BM samples derived from patients treated with teclistamab or talquetamab revealed that high frequencies of PD-1+ CD4+ T cells, CTLA4+ CD4+ T cells, and CD38+ CD4+ T cells were associated with primary resistance. Although this lack of response was linked to a modest increase in the expression of inhibitory receptors, increasing T-cell/multiple myeloma cell ratios by adding extra T cells enhanced sensitivity to BsAb. Further, treatment with BsAb resulted in an increased proportion of T cells expressing exhaustion markers (PD-1, TIGIT, and TIM-3), which was accompanied by reduced T-cell proliferative potential and cytokine secretion, as well as impaired antitumor efficacy in ex vivo experiments., Conclusions: Primary resistance is characterized by a low T-cell/multiple myeloma cell ratio and Treg-driven immunosuppression, whereas reduced T-cell fitness due to continuous BsAb-mediated T-cell activation may contribute to the development of acquired resistance., (©2024 American Association for Cancer Research.)
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- 2024
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15. Response to DA-EPOCH-R is associated with activation of 'fitter' cytotoxic T-cells in patients with newly diagnosed double and triple hit high-grade B-cell lymphoma.
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De Jonge AV, Bruins WSC, Duetz C, Korst CLBM, Rentenaar R, Cosovic M, Eken M, Kersten MJ, Sandberg Y, Van Rijn RS, Fijnheer R, Mutsaers P, Vergote VKJ, Issa D, Beeker A, Bilgin YM, Visser O, Van Werkhoven E, Roemer MGM, Chamuleau MED, and Mutis T
- Abstract
Not available.
- Published
- 2024
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16. Myelodysplastic neoplasms dissected into indolent, leukaemic and unfavourable subtypes by computational clustering of haematopoietic stem and progenitor cells.
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van Spronsen MF, Van Gassen S, Duetz C, Westers TM, Saeys Y, and van de Loosdrecht AA
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- Humans, Aged, Middle Aged, Male, Female, Prognosis, Adult, Aged, 80 and over, Antigens, CD34 metabolism, Leukemia, Myeloid, Acute pathology, Immunophenotyping, Cluster Analysis, Flow Cytometry methods, Case-Control Studies, Myelodysplastic Syndromes pathology, Hematopoietic Stem Cells pathology, Hematopoietic Stem Cells metabolism
- Abstract
Myelodysplastic neoplasms (MDS) encompass haematological malignancies, which are characterised by dysplasia, ineffective haematopoiesis and the risk of progression towards acute myeloid leukaemia (AML). Myelodysplastic neoplasms are notorious for their heterogeneity: clinical outcomes range from a near-normal life expectancy to leukaemic transformation or premature death due to cytopenia. The Molecular International Prognostic Scoring System made progress in the dissection of MDS by clinical outcomes. To contribute to the risk stratification of MDS by immunophenotypic profiles, this study performed computational clustering of flow cytometry data of CD34
+ cells in 67 MDS, 67 AML patients and 49 controls. Our data revealed heterogeneity also within the MDS-derived CD34+ compartment. In MDS, maintenance of lymphoid progenitors and megakaryocytic-erythroid progenitors predicted favourable outcomes, whereas expansion of granulocyte-monocyte progenitors increased the risk of leukaemic transformation. The proliferation of haematopoietic stem cells and common myeloid progenitors with downregulated CD44 expression, suggestive of impaired haematopoietic differentiation, characterised a distinct MDS subtype with a poor overall survival. This exploratory study demonstrates the prognostic value of known and previously unexplored CD34+ populations and suggests the feasibility of dissecting MDS into a more indolent, a leukaemic and another unfavourable subtype., (© 2024. The Author(s).)- Published
- 2024
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17. Distinct peripheral T-cell and NK-cell profiles in HGBL-MYC/BCL2 vs patients with DLBCL NOS.
- Author
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de Jonge AV, Duetz C, Bruins WSC, Korst CLBM, Rentenaar R, Cosovic M, Eken M, Twickler I, Nijland M, van der Poel MWM, de Heer K, Klerk CPW, Strobbe L, Oosterveld M, Boersma R, Koene HR, Roemer MGM, van Werkhoven E, Chamuleau MED, and Mutis T
- Subjects
- Humans, Proto-Oncogene Proteins c-bcl-2 genetics, T-Lymphocytes pathology, Killer Cells, Natural pathology, Cytokines, Tumor Microenvironment, Programmed Cell Death 1 Receptor, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Abstract: Patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBL-MYC/BCL2) respond poorly to immunochemotherapy compared with patients with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) without a MYC rearrangement. This suggests a negative impact of lymphoma-intrinsic MYC on the immune system. To investigate this, we compared circulating T cells and natural killer (NK) cells of patients with HGBL-MYC/BCL2 (n = 66), patients with DLBCL NOS (n = 53), and age-matched healthy donors (HDs; n = 16) by flow cytometry and performed proliferation, cytokine production, and cytotoxicity assays. Compared with HDs, both lymphoma subtypes displayed similar frequencies of CD8+ T cells but decreased CD4+ T cells. Regulatory T-cell (Treg) frequencies were reduced only in patients with DLBCL NOS. Activated (HLA-DR+/CD38+) T cells, PD-1+CD4+ T cells, and PD-1+Tregs were increased in both lymphoma subtypes, but PD-1+CD8+ T cells were increased only in HGBL-MYC/BCL2. Patients with DLBCL NOS, but not patients with HGBL-MYC/BCL2, exhibited higher frequencies of senescent T cells than HDs. Functional assays showed no overt differences between both lymphoma groups and HDs. Deeper analyses revealed that PD-1+ T cells of patients with HGBL-MYC/BCL2 were exhausted with impaired cytokine production and degranulation. Patients with DLBCL NOS, but not patients with HGBL-MYC/BCL2, exhibited higher frequencies of NK cells expressing inhibiting receptor NKG2A. Both lymphoma subtypes exhibited lower TIM-3+- and DNAM-1+-expressing NK cells. Although NK cells of patients with HGBL-MYC/BCL2 showed less degranulation, they were not defective in cytotoxicity. In conclusion, our results demonstrate an increased exhaustion in circulating T cells of patients with HGBL-MYC/BCL2. Nonetheless, the overall intact peripheral T-cell and NK-cell functions in these patients emphasize the importance of investigating potential immune evasion in the microenvironment of MYC-rearranged lymphomas., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
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18. Challenging the status flow: how artificial intelligence is advancing diagnosis of myelodysplastic neoplasms.
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Duetz C, Westers TM, and Van de Loosdrecht AA
- Subjects
- Humans, Artificial Intelligence, Myelodysplastic Syndromes diagnosis, Neoplasms
- Published
- 2023
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19. NK Cell Phenotype Is Associated With Response and Resistance to Daratumumab in Relapsed/Refractory Multiple Myeloma.
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Verkleij CPM, Frerichs KA, Broekmans MEC, Duetz C, O'Neill CA, Bruins WSC, Homan-Weert PM, Minnema MC, Levin MD, Broijl A, Bos GMJ, Kersten MJ, Klein SK, Shikhagaie MM, Casneuf T, Abraham Y, Smets T, Vanhoof G, Cortes-Selva D, van Steenbergen L, Ramos E, Verona RI, Krevvata M, Sonneveld P, Zweegman S, Mutis T, and van de Donk NWCJ
- Abstract
The CD38-targeting antibody daratumumab has marked activity in multiple myeloma (MM). Natural killer (NK) cells play an important role during daratumumab therapy by mediating antibody-dependent cellular cytotoxicity via their FcγRIII receptor (CD16), but they are also rapidly decreased following initiation of daratumumab treatment. We characterized the NK cell phenotype at baseline and during daratumumab monotherapy by flow cytometry and cytometry by time of flight to assess its impact on response and development of resistance (DARA-ATRA study; NCT02751255). At baseline, nonresponding patients had a significantly lower proportion of CD16
+ and granzyme B+ NK cells, and higher frequency of TIM-3+ and HLA-DR+ NK cells, consistent with a more activated/exhausted phenotype. These NK cell characteristics were also predictive of inferior progression-free survival and overall survival. Upon initiation of daratumumab treatment, NK cells were rapidly depleted. Persisting NK cells exhibited an activated and exhausted phenotype with reduced expression of CD16 and granzyme B, and increased expression of TIM-3 and HLA-DR. We observed that addition of healthy donor-derived purified NK cells to BM samples from patients with either primary or acquired daratumumab-resistance improved daratumumab-mediated MM cell killing. In conclusion, NK cell dysfunction plays a role in primary and acquired daratumumab resistance. This study supports the clinical evaluation of daratumumab combined with adoptive transfer of NK cells., Competing Interests: MCM has a consultancy or advisory role for Gilead Sciences, BMS, Alnylam, Janssen Cilag, Takeda, and Servier; all paid to employer, hospitality from Celgene. MDL serves in advisory boards for Roche, Janssen and Abbvia. AB receives honoraria from Celgene, Janssen, Amgen, Takeda, and Sanofi. MJK has received research support from Kite/Gilead, and honoraria from Kite/Gilead, Novartis, BMS/Celgene, Takeda, Roche, and Miltenyi Biotec (all paid to institution). MK, TC, YA, RIV, TS, GV, DCS, LvS, and ER are employed by Janssen. PS has received honoraria from Amgen, BMS, Celgene, Janssen, Karyopharm, Takeda, and receives research funding from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda. SZ has received research funding from Celgene, Takeda, Janssen, and serves in advisory boards for Janssen, Takeda, BMS, Oncopeptides and Sanofi, all paid to institution. TM has received research support from Janssen Pharmaceuticals, Takeda, Genmab, Novartis, and ONK Therapeutics. NWCJvdD has received research support from Janssen Pharmaceuticals, AMGEN, Celgene, Novartis, Cellectis, and BMS, and serves in advisory boards for Janssen Pharmaceuticals, AMGEN, Celgene, BMS, Takeda, Roche, Novartis, Bayer, Adaptive, and Servier. All the other authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)- Published
- 2023
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20. The flow cytometry myeloid progenitor count: A reproducible parameter for diagnosis and prognosis of myelodysplastic syndromes.
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Johansson U, McIver-Brown N, Cullen M, Duetz C, Dunlop A, Oelschlägel U, Psarra K, Subirá D, and Westers TM
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- Humans, Flow Cytometry methods, Bone Marrow, Bone Marrow Cells, Myeloid Progenitor Cells, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics
- Abstract
Background: The bone marrow blast count is central to the diagnosis and monitoring of myelodysplastic syndromes (MDS). It is an independent risk factor for worse prognosis whether based on the morphology blast count or the flow cytometry (FC) myeloid progenitor (MyP) count. It is a principal population in FC MDS analysis also because once defined; it provides significant contributions to the overall FC MDS score., Methods: We elected to investigate inter-analyst agreement for the most fundamental parameter of the FC MDS diagnostic score: the MyP count. A common gating strategy was agreed and used by seven cytometrists for blind analysis of 34 routine bone marrows sent for MDS work-up. Additionally, we compared the results with a computational approach., Results: Concordance was excellent: Intraclass correlation was 0.993 whether measuring %MyP of total cells or CD45+ cells, and no significant difference was observed between files from different centers or for samples with abnormal MyP phenotypes. Computational and manual results were similar. Applying the common strategy to individual laboratories' control cohorts produced similar MyP reference ranges across centers., Conclusion: The FC MyP count offers a reliable diagnostic and prognostic measurement in MDS. The use of manual and computational approaches side by side may allow for optimizing both strategies. Considering its known prognostic power, the MyP count could be considered a useful and reliable addition to existing prognostic scoring systems., (© 2021 International Clinical Cytometry Society.)
- Published
- 2023
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21. Characterization of myelodysplastic syndromes hematopoietic stem and progenitor cells using mass cytometry.
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Bachas C, Duetz C, van Spronsen MF, Verhoeff J, Garcia Vallejo JJ, Jansen JH, Cloos J, Westers TM, and van de Loosdrecht AA
- Subjects
- Humans, Flow Cytometry, Hematopoietic Stem Cells metabolism, Risk Factors, Myelodysplastic Syndromes metabolism, Leukemia, Myeloid, Acute genetics
- Abstract
Background: Myelodysplastic syndromes (MDS) at risk of transformation to acute myeloid leukemia (AML) are difficult to identify. The bone marrows of MDS patients harbor specific hematopoietic stem and progenitor cell (HSPC) abnormalities that may be associated with sub-types and risk-groups. Leukemia-associated characteristics of such cells may identify MDS patients at risk of progression to AML and provide insight in the pathobiology of MDS., Methods: Bone marrow samples from healthy donors (n = 10), low risk (n = 12) and high risk (n = 13) MDS patients were collected, in addition, AML samples for 5 out of 6 MDS patients that progressed. Mass cytometry was applied to assess expression of stem cell subset and leukemia-associated immunophenotype markers., Results: We analyzed the data using FlowSOM to cluster cells with similar expression of 10 commonly used stem cell markers. Metaclusters (n = 20) of these clusters represented populations of cells with a related phenotype, largely resembling known stem cell subsets. Within specific subsets, intra-cellular expression levels of pCREB, IkBα, or pS6 differed significantly between healthy bone marrow (HBM) and MDS or consecutive secondary AML samples. CD34, CD44, and CD49f expression was significantly increased in high risk MDS and AML-associated metaclusters. We identified MDS/sAML cells with aberrant phenotypes when compared to HBM. Such cells were observed in clusters of both primary MDS and secondary AML samples., Conclusions: High-dimensional mass cytometry and computational data analyses enabled characterization of HSPC subsets in MDS and identification of leukemia stem cell populations based on their immunophenotype. Stem cells in MDS that display leukemia-associated features may predict the risk of developing AML., (© 2022 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)
- Published
- 2023
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22. Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European LeukemiaNet International MDS-Flow Cytometry Working Group.
- Author
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van de Loosdrecht AA, Kern W, Porwit A, Valent P, Kordasti S, Cremers E, Alhan C, Duetz C, Dunlop A, Hobo W, Preijers F, Wagner-Ballon O, Chapuis N, Fontenay M, Bettelheim P, Eidenschink-Brodersen L, Font P, Johansson U, Loken MR, Te Marvelde JG, Matarraz S, Ogata K, Oelschlaegel U, Orfao A, Psarra K, Subirá D, Wells DA, Béné MC, Della Porta MG, Burbury K, Bellos F, van der Velden VHJ, Westers TM, Saft L, and Ireland R
- Subjects
- Humans, Flow Cytometry, Myelodysplastic Syndromes diagnosis
- Abstract
This article discusses the rationale for inclusion of flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias of uncertain origin and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group (ELN iMDS Flow WG). The WHO 2016 classification recognizes that FCM contributes to the diagnosis of MDS and may be useful for prognostication, prediction, and evaluation of response to therapy and follow-up of MDS patients., (© 2021 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)
- Published
- 2023
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23. Flow cytometric analysis of myelodysplasia: Pre-analytical and technical issues-Recommendations from the European LeukemiaNet.
- Author
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van der Velden VHJ, Preijers F, Johansson U, Westers TM, Dunlop A, Porwit A, Béné MC, Valent P, Te Marvelde J, Wagner-Ballon O, Oelschlaegel U, Saft L, Kordasti S, Ireland R, Cremers E, Alhan C, Duetz C, Hobo W, Chapuis N, Fontenay M, Bettelheim P, Eidenshink-Brodersen L, Font P, Loken MR, Matarraz S, Ogata K, Orfao A, Psarra K, Subirá D, Wells DA, Della Porta MG, Burbury K, Bellos F, Weiß E, Kern W, and van de Loosdrecht A
- Subjects
- Humans, Flow Cytometry methods, Reference Standards, Biological Assay, Fluorescent Dyes, Myelodysplastic Syndromes diagnosis
- Abstract
Background: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures., Methods: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group., Results: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies., Conclusions: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice., (© 2021 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)
- Published
- 2023
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24. Multiparameter flow cytometry in the evaluation of myelodysplasia: Analytical issues: Recommendations from the European LeukemiaNet/International Myelodysplastic Syndrome Flow Cytometry Working Group.
- Author
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Porwit A, Béné MC, Duetz C, Matarraz S, Oelschlaegel U, Westers TM, Wagner-Ballon O, Kordasti S, Valent P, Preijers F, Alhan C, Bellos F, Bettelheim P, Burbury K, Chapuis N, Cremers E, Della Porta MG, Dunlop A, Eidenschink-Brodersen L, Font P, Fontenay M, Hobo W, Ireland R, Johansson U, Loken MR, Ogata K, Orfao A, Psarra K, Saft L, Subira D, Te Marvelde J, Wells DA, van der Velden VHJ, Kern W, and van de Loosdrecht AA
- Subjects
- Humans, Flow Cytometry methods, Antigens, CD34, Granulocytes pathology, Monocytes pathology, Immunophenotyping, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes pathology
- Abstract
Multiparameter flow cytometry (MFC) is one of the essential ancillary methods in bone marrow (BM) investigation of patients with cytopenia and suspected myelodysplastic syndrome (MDS). MFC can also be applied in the follow-up of MDS patients undergoing treatment. This document summarizes recommendations from the International/European Leukemia Net Working Group for Flow Cytometry in Myelodysplastic Syndromes (ELN iMDS Flow) on the analytical issues in MFC for the diagnostic work-up of MDS. Recommendations for the analysis of several BM cell subsets such as myeloid precursors, maturing granulocytic and monocytic components and erythropoiesis are given. A core set of 17 markers identified as independently related to a cytomorphologic diagnosis of myelodysplasia is suggested as mandatory for MFC evaluation of BM in a patient with cytopenia. A myeloid precursor cell (CD34
+ CD19- ) count >3% should be considered immunophenotypically indicative of myelodysplasia. However, MFC results should always be evaluated as part of an integrated hematopathology work-up. Looking forward, several machine-learning-based analytical tools of interest should be applied in parallel to conventional analytical methods to investigate their usefulness in integrated diagnostics, risk stratification, and potentially even in the evaluation of response to therapy, based on MFC data. In addition, compiling large uniform datasets is desirable, as most of the machine-learning-based methods tend to perform better with larger numbers of investigated samples, especially in such a heterogeneous disease as MDS., (© 2022 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)- Published
- 2023
- Full Text
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25. The wider perspective: twenty years of clinical trials in myelodysplastic syndromes.
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Duetz C, Cucchi DGJ, Polak TB, Janssen JJWM, Ossenkoppele GJ, Estey EH, and van de Loosdrecht AA
- Subjects
- Clinical Decision-Making, Clinical Trials as Topic, Combined Modality Therapy, Disease Management, Disease Progression, Humans, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes etiology, Prognosis, Treatment Outcome, Myelodysplastic Syndromes therapy
- Abstract
Most patients with myelodysplastic syndromes (MDS) require therapeutic intervention. However, there are few approved treatments for MDS. To explore reasons, we searched clinicaltrials.gov and clinicaltrialsregister.eu for MDS trials from 2000 to 2020. We assessed which agents were under investigation and analysed clinical trial characteristics and continuation rates from phase I to II to III to approval. As such, we identified 384 unique agents in 426 phase I, 430 phase II and 48 phase III trials. Success rates for phase III trials and agents were low, and MDS trials took markedly longer to complete than the average clinical trial. Although success rates were higher when MDS-specific phase I trials were conducted, 52% of the agents had not been evaluated in a phase I trial for MDS. MDS trials often failed to include quality of life, an especially important outcome for older MDS patients. Our work identifies factors potentially contributing to the paucity of available agents for MDS. We suggest a framework to improve clinical research in MDS that might ultimately augment the number of available agents., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
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26. Computational flow cytometry as a diagnostic tool in suspected-myelodysplastic syndromes.
- Author
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Duetz C, Van Gassen S, Westers TM, van Spronsen MF, Bachas C, Saeys Y, and van de Loosdrecht AA
- Subjects
- Cohort Studies, Cytogenetic Analysis, Flow Cytometry, Humans, Immunophenotyping, Myelodysplastic Syndromes diagnosis
- Abstract
The diagnostic work-up of patients suspected for myelodysplastic syndromes is challenging and mainly relies on bone marrow morphology and cytogenetics. In this study, we developed and prospectively validated a fully computational tool for flow cytometry diagnostics in suspected-MDS. The computational diagnostic workflow consists of methods for pre-processing flow cytometry data, followed by a cell population detection method (FlowSOM) and a machine learning classifier (Random Forest). Based on a six tubes FC panel, the workflow obtained a 90% sensitivity and 93% specificity in an independent validation cohort. For practical advantages (e.g., reduced processing time and costs), a second computational diagnostic workflow was trained, solely based on the best performing single tube of the training cohort. This workflow obtained 97% sensitivity and 95% specificity in the prospective validation cohort. Both workflows outperformed the conventional, expert analyzed flow cytometry scores for diagnosis with respect to accuracy, objectivity and time investment (less than 2 min per patient)., (© 2021 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.)
- Published
- 2021
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27. Distinct bone marrow immunophenotypic features define the splicing factor 3B subunit 1 (SF3B1)-mutant myelodysplastic syndromes subtype.
- Author
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Duetz C, Westers TM, In 't Hout FEM, Cremers EMP, Alhan C, Venniker-Punt B, Visser-Wisselaar HA, Chitu DA, de Graaf AO, Smit L, Jansen JH, and van de Loosdrecht AA
- Subjects
- Female, Humans, Male, Bone Marrow Cells immunology, Chromosomes, Human, Pair 5 genetics, Chromosomes, Human, Pair 5 immunology, Gene Deletion, Immunophenotyping, Myelodysplastic Syndromes classification, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes immunology, Phosphoproteins genetics, Phosphoproteins immunology, RNA Splicing Factors genetics, RNA Splicing Factors immunology
- Abstract
Splicing factor 3B subunit 1 (SF3B1) mutations define a distinct myelodysplastic syndromes (MDS) patient group with a relatively favourable disease course and high response rates to luspatercept. Few data are available on bone marrow phenotype beyond ring sideroblasts in this subgroup of patients with MDS. In the present study, we identified immunophenotypic erythroid, myelomonocyte and progenitor features associated with SF3B1 mutations. In addition, we illustrate that SF3B1-mutation type is associated with distinct immunophenotypic features, and show the impact of co-occurrence of a SF3B1 mutation and a deletion of chromosome 5q on bone marrow immunophenotype. These genotype-phenotype associations and phenotypic subtypes within SF3B1-MDS provide leads that may further refine prognostication and therapeutic strategies for this particular MDS subgroup., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2021
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28. Computational analysis of flow cytometry data in hematological malignancies: future clinical practice?
- Author
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Duetz C, Bachas C, Westers TM, and van de Loosdrecht AA
- Subjects
- Computational Biology methods, Data Analysis, Humans, Translational Research, Biomedical, Flow Cytometry methods, Hematologic Neoplasms pathology
- Abstract
Purpose of Review: This review outlines the advancements that have been made in computational analysis for clinical flow cytometry data in hematological malignancies., Recent Findings: In recent years, computational analysis methods have been applied to clinical flow cytometry data of hematological malignancies with promising results. Most studies combined dimension reduction (principle component analysis) or clustering methods (FlowSOM, generalized mixture models) with machine learning classifiers (support vector machines, random forest). For diagnosis and classification of hematological malignancies, many studies have reported results concordant with manual expert analysis, including B-cell chronic lymphoid leukemia detection and acute leukemia classification. Other studies, e.g. concerning diagnosis of myelodysplastic syndromes and classification of lymphoma, have shown to be able to increase diagnostic accuracy. With respect to treatment response monitoring, studies have focused on, for example, computational minimal residual disease detection in multiple myeloma and posttreatment classification of healthy or diseased in acute myeloid leukemia. The results of these studies are encouraging, although accurate relapse prediction remains challenging. To facilitate clinical implementation, collaboration and (prospective) validation in multicenter setting are necessary., Summary: Computational analysis methods for clinical flow cytometry data hold the potential to increase ease of use, objectivity and accuracy in the clinical work-up of hematological malignancies.
- Published
- 2020
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29. Macroscopic hematuria as presenting symptom of celiac disease.
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Duetz C, Houtenbos I, and de Roij van Zuijdewijn CLM
- Subjects
- Celiac Disease diet therapy, Diagnosis, Differential, Humans, Male, Middle Aged, Treatment Outcome, Vitamin K Deficiency complications, Celiac Disease complications, Celiac Disease diagnosis, Hematuria etiology
- Abstract
A 47-year old man was admitted for macroscopic hematuria and spontaneous hematomas. Laboratory results showed a prolonged partial thromboplastin time (PTT), a prolonged activated partial thromboplastin time (APTT) and a severe vitamin K deficiency. The underlying cause proved to be vitamin K malabsorption due to previously undiagnosed celiac disease, possibly provoked by oral antibiotic administration.
- Published
- 2019
30. Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic Syndromes.
- Author
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Duetz C, Westers TM, and van de Loosdrecht AA
- Subjects
- Algorithms, Disease Progression, Humans, Flow Cytometry methods, Myelodysplastic Syndromes diagnosis
- Abstract
Myelodysplastic syndromes (MDS) are a challenging group of diseases for clinicians and researchers, as both disease course and pathobiology are highly heterogeneous. In (suspected) MDS patients, multi-parameter flow cytometry can aid in establishing diagnosis, risk stratification and choice of therapy. This review addresses the developments and future directions of multi-parameter flow cytometry scores in MDS. Additionally, we propose an integrated diagnostic algorithm for suspected MDS., (© 2018 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2019
- Full Text
- View/download PDF
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