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123 results on '"Vekemans M"'

3. Diagnostic Yield of Chromosomal Microarray Analysis in Fetuses With Isolated Increased Nuchal Translucency: A French Multicenter Study

Author

Egloff, M., Hervé, B., Quibel, T., Jaillard, S., Le Bouar, G., Uguen, K., Saliou, A.-H., Valduga, M., Perdriolle, E., Coutton, C., Coston, A.-L., Coussement, A., Anselem, O., Missirian, C., Bretelle, F., Prieur, F., Fanget, C., Muti, C., Jacquemot, M.-C., Beneteau, C., Le Vaillant, C., Vekemans, M., Salomon, L. J., Vialard, F., and Malan, V.

Published
2019
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6. P13 IXAZOMIB, DARATUMUMAB AND LOW-DOSE DEXAMETHASONE IN INTERMEDIATE-FIT PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA; RESULTS OF THE INDUCTION AND MAINTENANCE TREATMENT OF THE PHASE II HOVON 143 STUDY

Author

Groen, K., primary, Stege, C., additional, Nasserinejad, K., additional, de Heer, K., additional, van Kampen, R., additional, Leys, R., additional, Thielen, N., additional, Westerman, M., additional, Wu, K., additional, Ludwig, I., additional, Issa, D., additional, Velders, G., additional, Vekemans, M., additional, van de Donk, N., additional, Timmers, G., additional, de Boer, F., additional, Tick, L., additional, van der Spek, E., additional, de Waal, E., additional, Sohne, M., additional, Sonneveld, P., additional, Nijhof, I., additional, Klein, S., additional, Levin, M., additional, Ypma, P., additional, and Zweegman, S., additional

Published
2023
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7. Correction: Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS

Author

Ossenkoppele, G. J., Breems, D. A., Stuessi, G., van Norden, Y., Bargetzi, M., Biemond, B. J., A von dem Borne, P., Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, C., Huls, G., Janssen, J. J. J. W., Jaspers, A., Jongen-Lavrencic, M., de Jongh, E., Klein, S. K., van der Klift, M., van Marwijk Kooy, M., Maertens, J., Michaux, L., van der Poel, M. W. M., van Rhenen, A., Tick, L., Valk, P., Vekemans, M. C., van der Velden, W. J. F. M., de Weerdt, O., Pabst, T., Manz, M., and Löwenberg, B.

Published
2020
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8. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

Author

Versluis, J, in ‘t Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M -C, Legdeur, M -C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, and Cornelissen, J J

Published
2017
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9. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40–60 years

Author

Cornelissen, J J, Versluis, J, Passweg, J R, van Putten, W L J, Manz, M G, Maertens, J, Beverloo, H B, Valk, P J M, van Marwijk Kooy, M, Wijermans, P W, Schaafsma, M R, Biemond, B J, Vekemans, M-C, Breems, D A, Verdonck, L F, Fey, M F, Jongen-Lavrencic, M, Janssen, J J W M, Huls, G, Kuball, J, Pabst, T, Graux, C, Schouten, H C, Gratwohl, A, Vellenga, E, Ossenkoppele, G, and Löwenberg, B

Published
2015
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11. Diffuse vertebral marrow changes at MRI: Multiple myeloma or normal?

Author

UCL - SSS/IREC/IMAG - Pôle d'imagerie médicale, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de radiologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, Vande Berg, B C, Kirchgesner, T, Acid, S, Malghem, J, Vekemans, M C, Lecouvet, F E, UCL - SSS/IREC/IMAG - Pôle d'imagerie médicale, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de radiologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, Vande Berg, B C, Kirchgesner, T, Acid, S, Malghem, J, Vekemans, M C, and Lecouvet, F E

Abstract

Five MRI patterns of marrow involvement (diffuse, focal, combined diffuse and focal, variegated, and normal) are observed in patients with a marrow proliferative disorder including MM. The wide range of marrow involvement patterns in monoclonal plasma cell proliferative disorders mirrors that of their natural histories that can vary from indolent to rapidly lethal. MRI of the axial bone marrow contributes to stage these disorders, but it should not be obtained for disease detection and characterization because of its limited specificity and sensitivity. At MRI, diffuse benign hematopoietic marrow hyperplasia and marrow heterogeneities in elderly patients mimic the diffuse and variegated patterns observed in MM patients. Careful analysis of fat- and fluid-sensitive MR images and quantitative marrow assessment by using MRI and FDG-PET can contribute in differentiating these changes from those associated with neoplastic marrow infiltration, with some residual overlapping findings.

Published
2022

12. COVID-19: impact of vaccination in myeloma patients.

Author

UCL - SSS/DDUV/SIGN - Cell signalling, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service de biochimie médicale, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Hoornaert, E, Dachy, F, Hansenne, A, Bailly, S, van Maanen, A, Gruson, D, Vekemans, M-C, UCL - SSS/DDUV/SIGN - Cell signalling, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service de biochimie médicale, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Hoornaert, E, Dachy, F, Hansenne, A, Bailly, S, van Maanen, A, Gruson, D, and Vekemans, M-C

Abstract

No abstract available

Published
2022

13. P906: IXAZOMIB, DARATUMUMAB AND LOW DOSE DEXAMETHASONE IN FRAIL PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): RESULTS OF THE MAINTENANCE TREATMENT OF THE PHASE II HOVON 143 STUDY

Author

Groen, K., primary, Seefat, M., additional, Nasserinejad, K., additional, Stege, C. A., additional, van der Spek, E., additional, Bilgin, Y. M., additional, Kentos, A., additional, Sohne, M., additional, van Kampen, R. J., additional, Ludwig, I., additional, Thielen, N., additional, Durdu-Rayman, N., additional, de Graauw, N. C., additional, van de Donk, N. W., additional, de Waal, E. G., additional, Vekemans, M.-C., additional, Timmers, G. J., additional, van der Klift, M., additional, Soechit, S., additional, Geerts, P. A., additional, Silbermann, M. H., additional, Oosterveld, M., additional, Nijhof, I., additional, Sonneveld, P., additional, Klein, S. K., additional, Levin, M.-D., additional, and Zweegman, S., additional

Published
2022
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14. P12: TREATMENTS IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: RETROSPECTIVE CHART REVIEW OF REAL-WORLD OUTCOMES FOR STANDARD OF CARE

Author

Vekemans, M-C, primary, Delforge, M, additional, Anguille, S, additional, Depaus, J, additional, Meuleman, N, additional, Van de Velde, A, additional, Vande Broek, I, additional, Strens, D, additional, Van Hoorenbeeck, S, additional, Moorkens, EJ, additional, Diels, J, additional, Ghilotti, F, additional, Dalhuisen, S, additional, and Vandervennet, S, additional

Published
2022
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18. Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Author

Janssen, J. (Jeroen), Löwenberg, B. (Bob), Manz, M. (Markus), Bargetzi, M. (Mario), Biemond, B.J. (Bart), Borne, P.A.K. (Peter) von dem, Breems, D.A. (Dimitri), Brouwer, R.E. (Rolf), Chalandon, Y. (Yves), Deeren, D. (Dries), Efthymiou, A. (Anna), Gjertsen, B.-T. (Bjørn-Tore), Graux, C. (Carlos), Gregor, M. (Michael), Heim, D. (Dominik), Hess, U. (Urs), Hoogendoorn, M. (Mels), Jaspers, A. (Aurelie), Jie, A. (Asiong), Jongen-Lavrencic, M. (Mojca), Klein, S. (Saskia), Klift, M. (Marjolein) van der, Kuball, J. (Jürgen), van Lammeren - Venema, D. (Danielle), Legdeur, M.C.J.C. (M. C J C), Loosdrecht, A.A. (Arjan) van de, Maertens, J. (Johan), Kooy, M.M. (Marinus van Marwijk), Moors, I. (Ine), Nijziel, M.R. (Marten), van Obbergh, F. (Florence), Oosterveld, M. (Margriet), Pabst, T. (Thomas), van der Poel, M. (Marjolein), Sinnige, H. (Harm), Spertini, O. (Olivier), Terpstra, W. (Wim), Tick, L.W. (Lidwine), Velden, W.J.F.M. (Walter) van der, Vekemans, M.-C. (Marie-Christiane), Vellenga, E. (Edo), Weerdt, O. (Okke) de, Westerweel, P. (Peter), Stussi, G. (Georg), Norden, Y. (Yvette) van, Ossenkoppele, G.J. (Gert), Janssen, J. (Jeroen), Löwenberg, B. (Bob), Manz, M. (Markus), Bargetzi, M. (Mario), Biemond, B.J. (Bart), Borne, P.A.K. (Peter) von dem, Breems, D.A. (Dimitri), Brouwer, R.E. (Rolf), Chalandon, Y. (Yves), Deeren, D. (Dries), Efthymiou, A. (Anna), Gjertsen, B.-T. (Bjørn-Tore), Graux, C. (Carlos), Gregor, M. (Michael), Heim, D. (Dominik), Hess, U. (Urs), Hoogendoorn, M. (Mels), Jaspers, A. (Aurelie), Jie, A. (Asiong), Jongen-Lavrencic, M. (Mojca), Klein, S. (Saskia), Klift, M. (Marjolein) van der, Kuball, J. (Jürgen), van Lammeren - Venema, D. (Danielle), Legdeur, M.C.J.C. (M. C J C), Loosdrecht, A.A. (Arjan) van de, Maertens, J. (Johan), Kooy, M.M. (Marinus van Marwijk), Moors, I. (Ine), Nijziel, M.R. (Marten), van Obbergh, F. (Florence), Oosterveld, M. (Margriet), Pabst, T. (Thomas), van der Poel, M. (Marjolein), Sinnige, H. (Harm), Spertini, O. (Olivier), Terpstra, W. (Wim), Tick, L.W. (Lidwine), Velden, W.J.F.M. (Walter) van der, Vekemans, M.-C. (Marie-Christiane), Vellenga, E. (Edo), Weerdt, O. (Okke) de, Westerweel, P. (Peter), Stussi, G. (Georg), Norden, Y. (Yvette) van, and Ossenkoppele, G.J. (Gert)

Abstract

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation wa

Published
2021
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21. S145 PHASE 3 RANDOMIZED STUDY OF DARATUMUMAB + BORTEZOMIB/THALIDOMIDE/DEXAMETHASONE (D-VTD) VERSUS VTD IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PART 1 CASSIOPEIA RESULTS

Author

Moreau, P., primary, Attal, M., additional, Hulin, C., additional, Arnulf, B., additional, Belhadj, K., additional, Benboubker, L., additional, Béné, M. C., additional, Broijl, A., additional, Caillon, H., additional, Caillot, D., additional, Corre, J., additional, Delforge, M., additional, Dejoie, T., additional, Doyen, C., additional, Facon, T., additional, Sonntag, C., additional, Garderet, L., additional, Jie, K.-S., additional, Karlin, L., additional, Kuhnowski, F., additional, Lambert, J., additional, Leleu, X., additional, Lenain, P., additional, Macro, M., additional, Orsini-Piocelle, F., additional, Perrot, A., additional, Stoppa, A.-M., additional, van de Donk, N. W., additional, Wuilleme, S., additional, Zweegman, S., additional, Kolb, B., additional, Touzeau, C., additional, Roussel, M., additional, Tiab, M., additional, Marolleau, J.-P., additional, Meuleman, N., additional, Vekemans, M.-C., additional, Westerman, M., additional, Klein, S. K., additional, Levin, M.-D., additional, Escoffre-Barbe, M., additional, Eveillard, J.-R., additional, Garidi, R., additional, Ahmadi, T., additional, Zhuang, S., additional, Chiu, C., additional, Pei, L., additional, Vanquickelberghe, V., additional, de Boer, C., additional, Smith, E., additional, Deraedt, W., additional, Kampfenkel, T., additional, Schecter, J., additional, Vermeulen, J., additional, Avet-Loiseau, H., additional, and Sonneveld, P., additional

Published
2019
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22. GRAFT VERSUS LEUKEMIA EFFECT OF ALLOGENEIC STEM CELL TRANSPLANTATION AND MINIMAL RESIDUAL DISEASE IN PATIENTS WITH AML IN FIRST COMPLETE REMISSION

Author

Versluis, J., Kalin, B., Zeijlemaker, W., Passweg, J., Graux, C., Manz, M., Vekemans, M-C, Biemond, B., Legdeur, M-C, Kooy, M. van Marwijk, Janssen, J., Pabst, T., Lowenberg, B., Jongen-Lavrencic, M., Schuurhuis, G. J., Ossenkoppele, G., Cornelissen, J., Hematology laboratory, CCA - Cancer Treatment and quality of life, and Hematology

Published
2017

23. Diagnostic yield of chromosomal microarray analysis in fetuses with isolated increased nuchal translucency: a French multicenter study

Author

Egloff, M., primary, Hervé, B., additional, Quibel, T., additional, Jaillard, S., additional, Le Bouar, G., additional, Uguen, K., additional, Saliou, A.‐H., additional, Valduga, M., additional, Perdriolle, E., additional, Coutton, C., additional, Coston, A.‐L., additional, Coussement, A., additional, Anselem, O., additional, Missirian, C., additional, Bretelle, F., additional, Prieur, F., additional, Fanget, C., additional, Muti, C., additional, Jacquemot, M.‐C., additional, Beneteau, C., additional, Le Vaillant, C., additional, Vekemans, M., additional, Salomon, L. J., additional, Vialard, F., additional, and Malan, V., additional

Published
2018
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24. Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia

Author

Craddock, C.F. (Charles), Versluis, J. (Jurjen), Labopin, M. (Myriam), Socie, G. (Gerard), Huynh, A. (Anne), Deconinck, E. (Eric), Volin, L. (Liisa), Milpied, N., Bourhis, J.H. (J. H.), Rambaldi, A. (Alessandro), Chevallier, P. (Patrice), Blaise, D. (Didier), Manz, M. (M.), Vellenga, E. (Edo), Vekemans, M.-C. (Marie-Christiane), Maertens, J. (Johan), Passweg, J. (Jakob Robert), Vyas, P. (Paresh), Schmid, C. (Christoph), Löwenberg, B. (Bob), Ossenkoppele, G.J. (Gert), Mohty, M. (Mohamad), Cornelissen, J.J. (Jan), Nagler, A. (Arnon), Craddock, C.F. (Charles), Versluis, J. (Jurjen), Labopin, M. (Myriam), Socie, G. (Gerard), Huynh, A. (Anne), Deconinck, E. (Eric), Volin, L. (Liisa), Milpied, N., Bourhis, J.H. (J. H.), Rambaldi, A. (Alessandro), Chevallier, P. (Patrice), Blaise, D. (Didier), Manz, M. (M.), Vellenga, E. (Edo), Vekemans, M.-C. (Marie-Christiane), Maertens, J. (Johan), Passweg, J. (Jakob Robert), Vyas, P. (Paresh), Schmid, C. (Christoph), Löwenberg, B. (Bob), Ossenkoppele, G.J. (Gert), Mohty, M. (Mohamad), Cornelissen, J.J. (Jan), and Nagler, A. (Arnon)

Abstract

Background: Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). Aims: The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. Materials and Methods: We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. Results: In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). Discussion and Conclusion: Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical set

Published
2018
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25. Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice

Author

Jurczyszyn, A. Grzasko, N. Gozzetti, A. Czepiel, J. Cerase, A. Hungria, V. Crusoe, E. Silva Dias, A.L.M. Vij, R. Fiala, M.A. Caers, J. Rasche, L. Nooka, A.K. Lonial, S. Vesole, D.H. Philip, S. Gangatharan, S. Druzd-Sitek, A. Walewski, J. Corso, A. Cocito, F. Vekemans, M.-C.M. Atilla, E. Beksac, M. Leleu, X. Davila, J. Badros, A. Aneja, E. Abildgaard, N. Kastritis, E. Fantl, D. Schutz, N. Pika, T. Butrym, A. Olszewska-Szopa, M. Usnarska-Zubkiewicz, L. Usmani, S.Z. Nahi, H. Chim, C.S. Shustik, C. Madry, K. Lentzsch, S. Swiderska, A. Helbig, G. Guzicka-Kazimierczak, R. Lendvai, N. Waage, A. Andersen, K.T. Murakami, H. Zweegman, S. Castillo, J.J.

Abstract

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P

Published
2016

26. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

Hofstra, L.M. Sauvageot, N. Albert, J. Alexiev, I. Garcia, F. Struck, D. Van De Vijver, D.A.M.C. Åsjö, B. Beshkov, D. Coughlan, S. Descamps, D. Griskevicius, A. Hamouda, O. Horban, A. Van Kasteren, M. Kolupajeva, T. Kostrikis, L.G. Liitsola, K. Linka, M. Mor, O. Nielsen, C. Otelea, D. Paraskevis, D. Paredes, R. Poljak, M. Puchhammer-Stöckl, E. Sönnerborg, A. Staneková, D. Stanojevic, M. Van Laethem, K. Zazzi, M. Lepej, S.Z. Boucher, C.A.B. Schmit, J.-C. Wensing, A.M.J. Puchhammer-Stockl, E. Sarcletti, M. Schmied, B. Geit, M. Balluch, G. Vandamme, A.-M. Vercauteren, J. Derdelinckx, I. Sasse, A. Bogaert, M. Ceunen, H. De Roo, A. De Wit, S. Echahidi, F. Fransen, K. Goffard, J.-C. Goubau, P. Goudeseune, E. Yombi, J.-C. Lacor, P. Liesnard, C. Moutschen, M. Pierard, D. Rens, R. Schrooten, Y. Vaira, D. Vandekerckhove, L.P.R. Van Den Heuvel, A. Van Der Gucht, B. Van Ranst, M. Van Wijngaerden, E. Vandercam, B. Vekemans, M. Verhofstede, C. Clumeck, N. Begovac, J. Demetriades, I. Kousiappa, I. Demetriou, V. Hezka, J. Maly, M. Machala, L. Jørgensen, L.B. Gerstoft, J. Mathiesen, L. Pedersen, C. Nielsen, H. Laursen, A. Kvinesdal, B. Ristola, M. Suni, J. Sutinen, J. Assoumou, L. Castor, G. Grude, M. Flandre, P. Storto, A. Kücherer, C. Berg, T. Braun, P. Poggensee, G. Däumer, M. Eberle, J. Heiken, H. Kaiser, R. Knechten, H. Korn, K. Müller, H. Neifer, S. Schmidt, B. Walter, H. Gunsenheimer-Bartmeyer, B. Harrer, T. Hatzakis, A. Zavitsanou, A. Vassilakis, A. Lazanas, M. Chini, M. Lioni, A. Sakka, V. Kourkounti, S. Paparizos, V. Antoniadou, A. Papadopoulos, A. Poulakou, G. Katsarolis, I. Protopapas, K. Chryssos, G. Drimis, S. Gargalianos, P. Xylomenos, G. Lourida, G. Psichogiou, M. Daikos, G.L. Sipsas, N.V. Kontos, A. Gamaletsou, M.N. Koratzanis, G. Sambatakou, E. Mariolis, H. Skoutelis, A. Papastamopoulos, V. Georgiou, O. Panagopoulos, P. Maltezos, E. De Gascun, C. Byrne, C. Duffy, M. Bergin, C. Reidy, D. Farrell, G. Lambert, J. O'Connor, E. Rochford, A. Low, J. Coakely, P. O'Dea, S. Hall, W. Levi, I. Chemtob, D. Grossman, Z. De Luca, A. Balotta, C. Riva, C. Mussini, C. Caramma, I. Capetti, A. Colombo, M.C. Rossi, C. Prati, F. Tramuto, F. Vitale, F. Ciccozzi, M. Angarano, G. Rezza, G. Vasins, O. Lipnickiene, V. Hemmer, R. Arendt, V. Michaux, C. Staub, T. Sequin-Devaux, C. Van Kessel, A. Van Bentum, P.H.M. Brinkman, K. Connell, B.J. Van Der Ende, M.E. Hoepelman, I.M. Kuipers, M. Langebeek, N. Richter, C. Santegoets, R.M.W.J. Schrijnders-Gudde, L. Schuurman, R. Van De Ven, B.J.M. Kran, A.-M.B. Ormaasen, V. Aavitsland, P. Stanczak, J.J. Stanczak, G.P. Firlag-Burkacka, E. Wiercinska-Drapalo, A. Jablonowska, E. Maolepsza, E. Leszczyszyn-Pynka, M. Szata, W. Camacho, R. Palma, C. Borges, F. Paixão, T. Duque, V. Araújo, F. Paraschiv, S. Tudor, A.M. Cernat, R. Chiriac, C. Dumitrescu, F. Prisecariu, L.J. Jevtovic, Dj. Salemovic, D. Stanekova, D. Habekova, M. Chabadová, Z. Drobkova, T. Bukovinova, P. Shunnar, A. Truska, P. Lunar, M. Babic, D. Tomazic, J. Vidmar, L. Vovko, T. Karner, P. Monge, S. Moreno, S. Del Amo, J. Asensi, V. Sirvent, J.L. De Mendoza, C. Delgado, R. Gutiérrez, F. Berenguer, J. Garcia-Bujalance, S. Stella, N. De Los Santos, I. Blanco, J.R. Dalmau, D. Rivero, M. Segura, F. Elías, M.J.P. Alvarez, M. Chueca, N. Rodríguez-Martín, C. Vidal, C. Palomares, J.C. Viciana, I. Viciana, P. Cordoba, J. Aguilera, A. Domingo, P. Galindo, M.J. Miralles, C. Del Pozo, M.A. Ribera, E. Iribarren, J.A. Ruiz, L. De La Torre, J. Vidal, F. Clotet, B. Heidarian, A. Aperia-Peipke, K. Axelsson, M. Mild, M. Karlsson, A. Thalme, A. Navér, L. Bratt, G. Blaxhult, A. Gisslén, M. Svennerholm, B. Björkman, P. Säll, C. Mellgren, Å. Lindholm, A. Kuylenstierna, N. Montelius, R. Azimi, F. Johansson, B. Carlsson, M. Johansson, E. Ljungberg, B. Ekvall, H. Strand, A. Mäkitalo, S. Öberg, S. Holmblad, P. Höfer, M. Holmberg, H. Josefson, P. Ryding, U. Bergbrant, I. SPREAD Program

Abstract

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected. © The Author 2015.

Published
2016

27. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

Author

Moutschen, M., Hofstra, Laura Marije Arije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van, de Vijver, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios N., Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Zidovec Lepej, Snjezana, Boucher, Charles A. B., Schmit, Jean-Claude, Wensing, Annemarie M. J., Puchhammer-Stockl, E., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van, den Heuvel, Van, Der Gucht, Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Lepej, S. Z., Begovac, J., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Maly, M., Machala, L., Nielsen, C., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Liitsola, K., Ristola, M., Suni, J., Sutinen, J., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Zavitsanou, Assimina, Vassilakis, A., Lazanas, Marios C., Chini, Maria C., Lioni, A., Sakka, V., Kourkounti, Sofia, Paparizos, Vassilios A., Antoniadou, Anastasia C., Papadopoulos, Antonios I., Poulakou, Garyphallia G., Katsarolis, I., Protopapas, K., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Xylomenos, Georgios, Lourida, G., Psichogiou, Mina A., Daikos, George L., Sipsas, N. V., Kontos, Athanasios N., Gamaletsou, M. N., Koratzanis, Georgios, Sambatakou, H., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, Periklis, Maltezos, E., Coughlan, S., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., de Luca, A., Balotta, Claudia, Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M. J., Boucher, C. A. B., van, de Vijver, van Kessel, A., van Bentum, P. H. M., Brinkman, K., Connell, B. J., van, der Ende, Hoepelman, I. M., van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van, de Ven, Kran, A. -M B., Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, Ricardo J., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., del Amo, J., Asensi, V., Sirvent, J. L., de Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, Natalia C., de, los Santos, Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elıás, Marıá Jesús Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de, la Torre, Vidal, F., Clotet, B., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Säll, C., Mellgren, Å., Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., Öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Clinical sciences, Microbiology and Infection Control, Supporting clinical sciences, Clinicum, Department of Medicine, Virology, Cohorte de Adultos de la Red de Investigación en SIDA, Spain., SPREAD Program, [Hofstra,LM, Sauvageot,N, Struck,D, Schmit,JC ] Luxembourg Institute of Health, Luxembourg. [Hofstra,LM, Wensing,AMJ] Department of Virology, University Medical Center Utrecht, The Netherlands. [Albert,J, Sönnerborg,A] Karolinska Institute, Solna. Karolinska University Hospital, Stockholm, Sweden. [Alexiev,I, Beshkov,D] National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria. [Garcia,F] Complejo Hospitalario Universitario de Granada. Instituto de Investigación IBS Granada, Spain. [Van de Vijver,DAMC, Boucher,CAB] Erasmus MC, University Medical Center, Rotterdam, The Netherlands. [Åsjö,B] University of Bergen, Norway. [Coughlan,S] University College Dublin, Ireland. [Descamps,D] AP-HP Groupe hospitalier Bichat-Claude Bernard. IAME INSERM UMR 1137. Université Paris Diderot Sorbonne Paris Cité, Paris, France. [Griskevicius,A] Lithuanian AIDS Center, Vilnius, Lithuania. [Hamouda,O] Robert Koch Institute, Berlin, Germany. [Horban,A] Hospital of Infectious Diseases, Warsaw, Poland. [Van Kasteren,M] St Elisabeth Hospital, Tilburg, The Netherlands. [Kolupajeva,T] Infectiology Center of Latvia, Riga. [Kostrikis,LG] University of Cyprus, Nicosia. [Liitsola,K] Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki, Finland. [Linka,M] National Reference Laboratory for HIV/AIDS, National Institute of Public Health, Prague, Czech Republic. [Mor,O] National HIV Reference Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, Israel. [Nielsen,C] Statens Serum Institut, Copenhagen, Denmark. [Otelea,D] National Institute for Infectious Diseases 'Prof. dr. Matei Bals', Bucharest, Romania. [Paraskevis,D] National Retrovirus Reference Center, University of Athens, Greece. [Paredes,R] IrsiCaixa Foundation, Badalona, Spain. [Poljak,M] Faculty of Medicine, Slovenian HIV/AIDS Reference Centre, University of Ljubljana, Slovenia. [Puchhammer-Stöckl,E] Medical University Vienna, Austria. [Staneková,D] Slovak Medical University, Bratislava, Slovakia. [Stanojevic,M] Faculty of Medicine, University of Belgrade, Serbia. [Van Laethem,K] Rega Institute for Medical Research, KU Leuven, Belgium. [Zazzi,M] University of Siena, Italy. [Zidovec Lepej,S] University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic', Zagreb, Croatia., This work was supported by a CORE grant of Fond National de la Recherche Luxembourg (grant number C12/BM/4011111–HIV molecular epidemiology in Europe). This work has been partially supported by the European Commission (fifth framework, grant number QLK2-CT-2001-01344, sixth framework, grant number LSHP-CT-2006-518211, DynaNets grant number 233847, seventh framework, CHAIN grant number 223131), Belgium: Belgian AIDS Reference Laboratory Fund, Belgian Fonds voor Wetenschappelijk Onderzoek (grant number G.0692.14), Cyprus: Cyprus Research Promotion Foundation (grant number Health/0104/22), Denmark: Danish AIDS Foundation, France: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales, Germany: Ministry of Health (grant number 1502-686-18), Ministry of Education and Research (grant number 01KI501), Italy: Fifth National Program on HIV/AIDS, Instituto Superiore di Sanità (grant numbers 40F.56 and 20D.1.6), Luxembourg: Fondation Recherche sur le SiDA and Ministry of Health, Republic of Serbia: Ministry of Education and Science (grant number 175024), Slovakia: project 'Center of Excellence of Environmental Health,' ITMS number 26240120033, based on supporting operational research and development program financed from the European Regional Development Fund, and Sweden: Swedish Research Council and Swedish Civil Contingencies Agency., APH - Health Behaviors & Chronic Diseases, Graduate School, Hofstra, LM, Sauvageot, N, Albert, J, Alexiev, I, Garcia, F, Struck, D, Van de Vijver, DA, Åsjö, B, Beshkov, D, Coughlan, S, Descamps, D, Griskevicius, A, Hamouda, O, Horban, A, Van Kasteren, M, Kolupajeva, T, Kostrikis, LG, Liitsola, K, Linka, M, Mor, O, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Staneková, D, Stanojevic, M, Van Laethem, K, Zazzi, M, Lepej, SZ, Boucher, CA, Schmit, JC, Wensing, AM, SPREAD program investigators, including Vitale F and Tramuto, F, Vandamme, Annemie, Vercauteren, Jurgen, Schrooten, Yoeri, Van Ranst, Marc, Van Wijngaerden, Eric, Derdelinckx, Inge, Camacho, Ricardo Jorge, Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]

Subjects
Male, Human immunodeficiency virus 1, Etravirine, RNA directed DNA polymerase inhibitor, darunavir, HIV Infections, Settore MED/42 - Igiene Generale E Applicata, Disciplines and Occupations::Health Occupations::Medicine::Public Health [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Salud pública, genetics, Inhibidores de proteasas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], atazanavir, media_common, transmission, Geographicals::Geographic Locations::Europe [Medical Subject Headings], 3. Good health, microbial sensitivity test, priority journal, Europe, HIV-1, antiretroviral therapy, drug resistance, HIV/AIDS, lamivudine, Reverse Transcriptase Inhibitors/pharmacology, anti human immunodeficiency virus agent, Drug, Microbiology (medical), medicine.medical_specialty, antiviral susceptibility, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], media_common.quotation_subject, 030106 microbiology, HIV Infections/drug therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings], Microbial Sensitivity Tests, RILPIVIRINE, Article, EFAVIRENZ, 03 medical and health sciences, transmitted drug resistance, SDG 3 - Good Health and Well-being, Humans, Transmission, human, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance [Medical Subject Headings], REVERSE-TRANSCRIPTASE INHIBITORS, Rilpivirina, INTEGRASE, MUTATIONS, abacavir, major clinical study, Virology, Infecciones por VIH, Regimen, Antiretroviral therapy, Drug resistance, Medicine (all), Infectious Diseases, chemistry, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Oxazines::Benzoxazines [Medical Subject Headings], Mutation, 0301 basic medicine, nevirapine, Communicable diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings], chemistry.chemical_compound, antiviral therapy, INFECTION, Medicine and Health Sciences, Prevalence, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [Medical Subject Headings], Viral, Non-U.S. Gov't, Reverse-transcriptase inhibitor, antiretrovirus agent, Research Support, Non-U.S. Gov't, Human immunodeficiency virus infected patient, Middle Aged, virology, PREVALENCE, Encuestas y Cuestionarios, ANTIRETROVIRAL TREATMENT, HIV-1/drug effects, HIV Protease Inhibitors/pharmacology, Rilpivirine, Reverse Transcriptase Inhibitors, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Female, HIV drug resistance, medicine.drug, Adult, Human immunodeficiency virus proteinase inhibitor, Chemicals and Drugs::Organic Chemicals::Nitriles::Rilpivirine [Medical Subject Headings], Efavirenz, Anti-HIV Agents, Research Support, Resistencia a medicamentos, Settore MED/17 - MALATTIE INFETTIVE, antiviral resistance, Internal medicine, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, Journal Article, medicine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings], abacavir plus lamivudine, Europa (Continente), HIV Protease Inhibitors, emtricitabine, nonhuman, Intervalos de confianza, Mutación, business.industry, HIV, prediction, Inhibidores de la transcriptasa inversa, Human immunodeficiency virus 1 infection, tenofovir, INDIVIDUALS, Drug Resistance, Viral/genetics, Benzoxazinas, ETRAVIRINE, drug effects, 3121 General medicine, internal medicine and other clinical medicine, Prevalencia, business
Abstract

Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors., Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)–infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%–9.5%) in 2008–2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

Published
2016
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28. Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS

Author

Ossenkoppele, G. J., Breems, D. A., Stuessi, G., van Norden, Y., Bargetzi, M., Biemond, B. J., A von dem Borne, P., Chalandon, Y., Cloos, J., Deeren, D., Fehr, M., Gjertsen, B., Graux, C., Huls, G., Janssen, J. J. J. W., Jaspers, A., Jongen-Lavrencic, M., de Jongh, E., Klein, S. K., van der Klift, M., van Marwijk Kooy, M., Maertens, J., Michaux, L., van der Poel, M. W. M., van Rhenen, A., Tick, L., Valk, P., Vekemans, M. C., van der Velden, W. J. F. M., de Weerdt, O., Pabst, T., Manz, M., and Löwenberg, B.

Abstract

More effective treatment modalities are urgently needed in patients with acute myeloid leukemia (AML) of older age. We hypothesized that adding lenalidomide to intensive standard chemotherapy might improve their outcome. After establishing a safe lenalidomide, dose elderly patients with AML were randomly assigned in this randomized Phase 2 study (n?=?222) to receive standard chemotherapy (“3?+?7”) with or without lenalidomide at a dose of 20?mg/day 1–21. In the second cycle, patients received cytarabine 1000?mg/m2twice daily on days 1–6 with or without lenalidomide (20?mg/day 1–21). The CR/CRi rates in the two arms were not different (69 vs. 66%). Event-free survival (EFS) at 36 months was 19% for the standard arm versus 21% for the lenalidomide arm and overall survival (OS) 35% vs. 30%, respectively. The frequencies and grade of adverse events were not significantly different between the treatment arms. Cardiovascular toxicities were rare and equally distributed between the arms. The results of the present study show that the addition of lenalidomide to standard remission induction chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR2294 in The NederlandsTrial Register (www.trialregister.nl).

Published
2020
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29. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

Author

MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, CTI Kuball, Cancer, Versluis, J, In 't Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M-C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, Cornelissen, J J, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, CTI Kuball, Cancer, Versluis, J, In 't Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M-C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, and Cornelissen, J J

Published
2017

30. Low Mannose-Binding Lectin Concentration Is Associated with Severe Infection in Patients with Hematological Cancer Who Are Undergoing Chemotherapy

Author

Vekemans, M., Robinson, J., Georgala, A., Heymans, C., Muanza, F., Paesmans, M., Klastersky, J., Barette, M., Meuleman, N., Huet, F., Calandra, T., Costantini, S., Ferrant, A., Mathissen, F., Axelsen, M., Marchetti, O., Aoun, M., Vekemans, M., Robinson, J., Georgala, A., Heymans, C., Muanza, F., Paesmans, M., Klastersky, J., Barette, M., Meuleman, N., Huet, F., Calandra, T., Costantini, S., Ferrant, A., Mathissen, F., Axelsen, M., Marchetti, O., and Aoun, M.

Abstract

Background. Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy. Methods. We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables. Results. We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P = .008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P < .001]). Conclusions. MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patients

Published
2017

31. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

Hofstra, L.M. Sauvageot, N. Albert, J. Alexiev, I. Garcia, F. Struck, D. Van De Vijver, D.A.M.C. Åsjö, B. Beshkov, D. Coughlan, S. Descamps, D. Griskevicius, A. Hamouda, O. Horban, A. Van Kasteren, M. Kolupajeva, T. Kostrikis, L.G. Liitsola, K. Linka, M. Mor, O. Nielsen, C. Otelea, D. Paraskevis, D. Paredes, R. Poljak, M. Puchhammer-Stöckl, E. Sönnerborg, A. Staneková, D. Stanojevic, M. Van Laethem, K. Zazzi, M. Lepej, S.Z. Boucher, C.A.B. Schmit, J.-C. Wensing, A.M.J. Puchhammer-Stockl, E. Sarcletti, M. Schmied, B. Geit, M. Balluch, G. Vandamme, A.-M. Vercauteren, J. Derdelinckx, I. Sasse, A. Bogaert, M. Ceunen, H. De Roo, A. De Wit, S. Echahidi, F. Fransen, K. Goffard, J.-C. Goubau, P. Goudeseune, E. Yombi, J.-C. Lacor, P. Liesnard, C. Moutschen, M. Pierard, D. Rens, R. Schrooten, Y. Vaira, D. Vandekerckhove, L.P.R. Van Den Heuvel, A. Van Der Gucht, B. Van Ranst, M. Van Wijngaerden, E. Vandercam, B. Vekemans, M. Verhofstede, C. Clumeck, N. Begovac, J. Demetriades, I. Kousiappa, I. Demetriou, V. Hezka, J. Maly, M. Machala, L. Jørgensen, L.B. Gerstoft, J. Mathiesen, L. Pedersen, C. Nielsen, H. Laursen, A. Kvinesdal, B. Ristola, M. Suni, J. Sutinen, J. Assoumou, L. Castor, G. Grude, M. Flandre, P. Storto, A. Kücherer, C. Berg, T. Braun, P. Poggensee, G. Däumer, M. Eberle, J. Heiken, H. Kaiser, R. Knechten, H. Korn, K. Müller, H. Neifer, S. Schmidt, B. Walter, H. Gunsenheimer-Bartmeyer, B. Harrer, T. Hatzakis, A. Zavitsanou, A. Vassilakis, A. Lazanas, M. Chini, M. Lioni, A. Sakka, V. Kourkounti, S. Paparizos, V. Antoniadou, A. Papadopoulos, A. Poulakou, G. Katsarolis, I. Protopapas, K. Chryssos, G. Drimis, S. Gargalianos, P. Xylomenos, G. Lourida, G. Psichogiou, M. Daikos, G.L. Sipsas, N.V. Kontos, A. Gamaletsou, M.N. Koratzanis, G. Sambatakou, E. Mariolis, H. Skoutelis, A. Papastamopoulos, V. Georgiou, O. Panagopoulos, P. Maltezos, E. De Gascun, C. Byrne, C. Duffy, M. Bergin, C. Reidy, D. Farrell, G. Lambert, J. O'Connor, E. Rochford, A. Low, J. Coakely, P. O&ap and Hofstra, L.M. Sauvageot, N. Albert, J. Alexiev, I. Garcia, F. Struck, D. Van De Vijver, D.A.M.C. Åsjö, B. Beshkov, D. Coughlan, S. Descamps, D. Griskevicius, A. Hamouda, O. Horban, A. Van Kasteren, M. Kolupajeva, T. Kostrikis, L.G. Liitsola, K. Linka, M. Mor, O. Nielsen, C. Otelea, D. Paraskevis, D. Paredes, R. Poljak, M. Puchhammer-Stöckl, E. Sönnerborg, A. Staneková, D. Stanojevic, M. Van Laethem, K. Zazzi, M. Lepej, S.Z. Boucher, C.A.B. Schmit, J.-C. Wensing, A.M.J. Puchhammer-Stockl, E. Sarcletti, M. Schmied, B. Geit, M. Balluch, G. Vandamme, A.-M. Vercauteren, J. Derdelinckx, I. Sasse, A. Bogaert, M. Ceunen, H. De Roo, A. De Wit, S. Echahidi, F. Fransen, K. Goffard, J.-C. Goubau, P. Goudeseune, E. Yombi, J.-C. Lacor, P. Liesnard, C. Moutschen, M. Pierard, D. Rens, R. Schrooten, Y. Vaira, D. Vandekerckhove, L.P.R. Van Den Heuvel, A. Van Der Gucht, B. Van Ranst, M. Van Wijngaerden, E. Vandercam, B. Vekemans, M. Verhofstede, C. Clumeck, N. Begovac, J. Demetriades, I. Kousiappa, I. Demetriou, V. Hezka, J. Maly, M. Machala, L. Jørgensen, L.B. Gerstoft, J. Mathiesen, L. Pedersen, C. Nielsen, H. Laursen, A. Kvinesdal, B. Ristola, M. Suni, J. Sutinen, J. Assoumou, L. Castor, G. Grude, M. Flandre, P. Storto, A. Kücherer, C. Berg, T. Braun, P. Poggensee, G. Däumer, M. Eberle, J. Heiken, H. Kaiser, R. Knechten, H. Korn, K. Müller, H. Neifer, S. Schmidt, B. Walter, H. Gunsenheimer-Bartmeyer, B. Harrer, T. Hatzakis, A. Zavitsanou, A. Vassilakis, A. Lazanas, M. Chini, M. Lioni, A. Sakka, V. Kourkounti, S. Paparizos, V. Antoniadou, A. Papadopoulos, A. Poulakou, G. Katsarolis, I. Protopapas, K. Chryssos, G. Drimis, S. Gargalianos, P. Xylomenos, G. Lourida, G. Psichogiou, M. Daikos, G.L. Sipsas, N.V. Kontos, A. Gamaletsou, M.N. Koratzanis, G. Sambatakou, E. Mariolis, H. Skoutelis, A. Papastamopoulos, V. Georgiou, O. Panagopoulos, P. Maltezos, E. De Gascun, C. Byrne, C. Duffy, M. Bergin, C. Reidy, D. Farrell, G. Lambert, J. O'Connor, E. Rochford, A. Low, J. Coakely, P. O&ap

Abstract

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected. © The Author 2015.

Published
2016

32. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, Puchhammer-Stockl, E., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. C., Goubau, P., Goudeseune, E., Yombi, J. C., Lacor, P., Liesnard, C., Moutschen, M., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P R, Van Den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., Nielsen, C., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Liitsola, K., Ristola, M., Suni, J., Sutinen, J., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Paraskevis, D., Hatzakis, A., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., Coughlan, S., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., Balotta, C., Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., Öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, Puchhammer-Stockl, E., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. C., Goubau, P., Goudeseune, E., Yombi, J. C., Lacor, P., Liesnard, C., Moutschen, M., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P R, Van Den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., Nielsen, C., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Liitsola, K., Ristola, M., Suni, J., Sutinen, J., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Paraskevis, D., Hatzakis, A., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., Coughlan, S., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., Balotta, C., Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., Öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., and Ryding, U.

Published
2016

33. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

Author

UCL - (SLuc) Service d'hématologie, Versluis, J, in ‘t Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M -C, Legdeur, M -C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, Cornelissen, J J, UCL - (SLuc) Service d'hématologie, Versluis, J, in ‘t Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M -C, Legdeur, M -C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, and Cornelissen, J J

Abstract

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.

Published
2016

34. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

MMB opleiding Arts microbioloog, MMB Medische Staf, Infection & Immunity, Onderzoek Bob Oranje, Brain, Cardiovasculaire Epi Team 1, MMB Research line 3a, MS Infectieziekten, Circulatory Health, MMB Staf diagnostiek, Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, Puchhammer-Stockl, E., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. C., Goubau, P., Goudeseune, E., Yombi, J. C., Lacor, P., Liesnard, C., Moutschen, M., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P R, Van Den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., Nielsen, C., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Liitsola, K., Ristola, M., Suni, J., Sutinen, J., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Paraskevis, D., Hatzakis, A., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., Coughlan, S., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., Balotta, C., Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., Öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., MMB opleiding Arts microbioloog, MMB Medische Staf, Infection & Immunity, Onderzoek Bob Oranje, Brain, Cardiovasculaire Epi Team 1, MMB Research line 3a, MS Infectieziekten, Circulatory Health, MMB Staf diagnostiek, Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, Puchhammer-Stockl, E., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. C., Goubau, P., Goudeseune, E., Yombi, J. C., Lacor, P., Liesnard, C., Moutschen, M., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P R, Van Den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., Nielsen, C., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Liitsola, K., Ristola, M., Suni, J., Sutinen, J., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Paraskevis, D., Hatzakis, A., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., Coughlan, S., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., Balotta, C., Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., Öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., and Ryding, U.

Published
2016

35. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

Universitat Rovira i Virgili, Hofstra LM, Sauvageot N, Albert J, Alexiev I, Garcia F, Struck D, Van de Vijver DAMC, Åsjö B, Beshkov D, Coughlan S, Descamps D, Griskevicius A, Hamouda O, Horban A, Van Kasteren M, Kolupajeva T, Kostrikis LG, Liitsola K, Linka M, Mor O, Nielsen C, Otelea D, Paraskevis D, Paredes R, Poljak M, Puchhammer-Stöckl E, Sönnerborg A, Staneková D, Stanojevic M, Van Laethem K, Zazzi M, Zidovec Lepej S, Boucher CAB, Schmit JC, Wensing AMJ,, Puchhammer-Stockl E, Sarcletti M, Schmied B, Geit M, Balluch G, Vandamme AM, Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Echahidi F, Fransen K, Goffard JC, Goubau P, Goudeseune E, Yombi JC, Lacor P, Liesnard C, Moutschen M, Pierard D, Rens R, Schrooten Y, Vaira D, Vandekerckhove LPR, Van den Heuvel A, Van Der Gucht B, Van Ranst M, Van Wijngaerden E, Vandercam B, Vekemans M, Verhofstede C, Clumeck N, Lepej SZ, Begovac J, Kostrikis L, Demetriades I, Kousiappa I, Demetriou V, Hezka J, Maly M, Machala L, Jørgensen LB, Gerstoft J, Mathiesen L, Pedersen C, Nielsen H, Laursen A, Kvinesdal B, Ristola M, Suni J, Sutinen J, Assoumou L, Castor G, Grude M, Flandre P, Storto A, Kücherer C, Berg T, Braun P, Poggensee G, Däumer M, Eberle J, Heiken H, Kaiser R, Knechten H, Korn K, Müller H, Neifer S, Schmidt B, Walter H, Gunsenheimer-Bartmeyer B, Harrer T, Hatzakis A, Zavitsanou A, Vassilakis A, Lazanas M, Chini M, Lioni A, Sakka V, Kourkounti S, Paparizos V, Antoniadou A, Papadopoulos A, Poulakou G, Katsarolis I, Protopapas K, Chryssos G, Drimis S, Gargalianos P, Xylomenos G, Lourida G, Psichogiou M, Daikos GL, Sipsas NV, Kontos A, Gamaletsou MN, Koratzanis G, Sambatakou H, Mariolis H, Skoutelis A, Papastamopoulos V, Georgiou O, Panagopoulos P, Maltezos E, De Gascun C, Byrne C, Duffy M, Bergin C, Reidy D, Farrell G, Lamber, Universitat Rovira i Virgili, and Hofstra LM, Sauvageot N, Albert J, Alexiev I, Garcia F, Struck D, Van de Vijver DAMC, Åsjö B, Beshkov D, Coughlan S, Descamps D, Griskevicius A, Hamouda O, Horban A, Van Kasteren M, Kolupajeva T, Kostrikis LG, Liitsola K, Linka M, Mor O, Nielsen C, Otelea D, Paraskevis D, Paredes R, Poljak M, Puchhammer-Stöckl E, Sönnerborg A, Staneková D, Stanojevic M, Van Laethem K, Zazzi M, Zidovec Lepej S, Boucher CAB, Schmit JC, Wensing AMJ,, Puchhammer-Stockl E, Sarcletti M, Schmied B, Geit M, Balluch G, Vandamme AM, Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Echahidi F, Fransen K, Goffard JC, Goubau P, Goudeseune E, Yombi JC, Lacor P, Liesnard C, Moutschen M, Pierard D, Rens R, Schrooten Y, Vaira D, Vandekerckhove LPR, Van den Heuvel A, Van Der Gucht B, Van Ranst M, Van Wijngaerden E, Vandercam B, Vekemans M, Verhofstede C, Clumeck N, Lepej SZ, Begovac J, Kostrikis L, Demetriades I, Kousiappa I, Demetriou V, Hezka J, Maly M, Machala L, Jørgensen LB, Gerstoft J, Mathiesen L, Pedersen C, Nielsen H, Laursen A, Kvinesdal B, Ristola M, Suni J, Sutinen J, Assoumou L, Castor G, Grude M, Flandre P, Storto A, Kücherer C, Berg T, Braun P, Poggensee G, Däumer M, Eberle J, Heiken H, Kaiser R, Knechten H, Korn K, Müller H, Neifer S, Schmidt B, Walter H, Gunsenheimer-Bartmeyer B, Harrer T, Hatzakis A, Zavitsanou A, Vassilakis A, Lazanas M, Chini M, Lioni A, Sakka V, Kourkounti S, Paparizos V, Antoniadou A, Papadopoulos A, Poulakou G, Katsarolis I, Protopapas K, Chryssos G, Drimis S, Gargalianos P, Xylomenos G, Lourida G, Psichogiou M, Daikos GL, Sipsas NV, Kontos A, Gamaletsou MN, Koratzanis G, Sambatakou H, Mariolis H, Skoutelis A, Papastamopoulos V, Georgiou O, Panagopoulos P, Maltezos E, De Gascun C, Byrne C, Duffy M, Bergin C, Reidy D, Farrell G, Lamber

Abstract

© The Author 2015. Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibi

Published
2016

36. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio

Author

Versluis, J, primary, in ‘t Hout, F E M, additional, Devillier, R, additional, van Putten, W L J, additional, Manz, M G, additional, Vekemans, M -C, additional, Legdeur, M -C, additional, Passweg, J R, additional, Maertens, J, additional, Kuball, J, additional, Biemond, B J, additional, Valk, P J M, additional, van der Reijden, B A, additional, Meloni, G, additional, Schouten, H C, additional, Vellenga, E, additional, Pabst, T, additional, Willemze, R, additional, Löwenberg, B, additional, Ossenkoppele, G, additional, Baron, F, additional, Huls, G, additional, and Cornelissen, J J, additional

Published
2016
Full Text
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37. F3 : Éruption bulleuse associée à un lymphome T angio-immunoblastique

Author

Colmant, C., primary, Sacré, L., additional, Janssens, P., additional, Schils, A., additional, Quaghebeur, C., additional, Marot, L., additional, Camboni, A., additional, Dachelet, C., additional, Vekemans, M.-C., additional, van den Neste, E., additional, Baeck, M., additional, Dekeuleneer, V., additional, and Tennstedt, D., additional

Published
2016
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38. Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia.

Author

Craddock, C., Versluis, J., Labopin, M., Socie, G., Huynh, A., Deconinck, E., Volin, L., Milpied, N., Bourhis, J. H., Rambaldi, A., Chevallier, P., Blaise, D., Manz, M., Vellenga, E., Vekemans, M‐C., Maertens, J., Passweg, J., Vyas, P., Schmid, C., and Löwenberg, B.

Subjects
MYELOID leukemia, CANCER chemotherapy, DISEASE relapse, CAUSES of death, CELLULAR therapy
Abstract

Background: Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT).Aims: The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized.Materials and Methods: We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone.Results: In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012).Discussion and Conclusion: Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings. [ABSTRACT FROM AUTHOR]

Published
2018
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39. Central Nervous System Involvement by Multiple Myeloma: a Multi-Institutional Retrospective Study of 172 Patients

Author

Jurczyszyn, A., primary, Gozzetti, A., additional, Cerase, A., additional, Hungria, V., additional, Crusoe, E., additional, Silva, A.L., additional, Vij, R., additional, Fiala, M.A., additional, Caers, J., additional, Rasche, L., additional, Nooka, A.K., additional, Lonial, S., additional, Vesole, D.H., additional, Philip, S., additional, Gangatharan, S., additional, Druzd-Sitek, A., additional, Walewski, J., additional, Corso, A., additional, Cocito, F., additional, Vekemans, M.-C.M., additional, Atilla, E., additional, Beksac, M., additional, Leleu, X., additional, Davila, J., additional, Badros, A., additional, Niesvizky, R., additional, Aneja, E., additional, Abildgaard, N., additional, Kastritis, E., additional, Fantl, D., additional, Schutz, N., additional, Pika, T., additional, Olszewska-Szopa, M., additional, Butrym, A., additional, Usnarska-Zubkiewicz, L., additional, Grz ko, N., additional, Usmani, S., additional, Nahi, H., additional, Chim, C.S., additional, Shustik, C., additional, dry, K.M., additional, Lentzsch, S., additional, widerska, A., additional, Helbig, G., additional, Guzicka-Kazimierczak, R., additional, Lendvain, N., additional, Waage, A., additional, Andersen, K.T., additional, Murakami, H., additional, Zweegman, S., additional, Skotnicki, A.B., additional, and Castillo, J.J., additional

Published
2015
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42. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1and FLT3-ITD allelic ratio

Author

Versluis, J, in ‘t Hout, F E M, Devillier, R, van Putten, W L J, Manz, M G, Vekemans, M -C, Legdeur, M -C, Passweg, J R, Maertens, J, Kuball, J, Biemond, B J, Valk, P J M, van der Reijden, B A, Meloni, G, Schouten, H C, Vellenga, E, Pabst, T, Willemze, R, Löwenberg, B, Ossenkoppele, G, Baron, F, Huls, G, and Cornelissen, J J

Abstract

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.

Published
2017
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44. Biallelic THOC6 pathogenic variants: Prenatal phenotype and review of the literature.

Author

Ruaud L, Roux N, Boutaud L, Bessières B, Ageorges F, Achaiaa A, Bole C, Nitschke P, Masson C, Vekemans M, Verloes A, and Attie-Bitach T

Subjects
Female, Humans, Male, Phenotype, Pregnancy, Exome Sequencing, Intellectual Disability genetics, Lymphangioma, Cystic, Microcephaly, Musculoskeletal Abnormalities genetics, RNA-Binding Proteins genetics
Abstract

Background: The THOC6 protein is a component of the THO complex. It is involved in mRNA transcription, processing and nuclear export. Interestingly molecular biallelic loss-of-function variants of the THOC6 gene were identified in the Beaulieu-Boycott-Innes syndrome (BBIS- OMIM # 613680). This condition was described in 17 patients and is characterized by a moderate to severe intellectual disability, facial dysmorphic features and severe birth defects such as heart, skeletal, ano-genital and renal congenital malformations., Methods: In the present study, we report on a new family with two affected sibs. The 6-year-old female had severe intellectual disability with autistic features, feeding difficulties, growth delay, facial dysmorphic, and congenital malformations (hand, skeletal and cardiac anomalies). The male fetus presented antenatally with a cystic hygroma associated with severe aortic and left ventricular hypoplasia. Autopsy, after termination of pregnancy at 15 weeks of gestation, showed facial dysmorphic, short right thumb and hypospadias., Results: Exome sequencing detected in both sibs compound heterozygous variants of the THOC6 gene (NM&#95;024339.3, GRCh37): the already reported c.[298T>A;700G>T;824G>A] haplotype and a novel variant c.977T>G, p.(Val326Gly)., Discussion: We made a review of the literature of 17 BBIS reported patients including our two siblings. Severe to moderate ID and congenital malformations were constant. Prenatal and postnatal failure to thrive were frequent. Brain MRI were not specific. Prenatal findings were reported in 40% of cases but we described the first case of cystic hygroma. The present study reports extends the prenatal delineation of the phenotypic features observed in association with the presence of THOC6 variants. In addition, it underscores the intrafamilial phenotypic variability observed in BBIS., (© 2022 Wiley Periodicals LLC.)

Published
2022
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45. Assessment 2 months after the administration of a 3rd dose mRNA: a new variant-adapted vaccine is expected.

Author

Tré-Hardy M, Cupaiolo R, Wilmet A, Antoine-Moussiaux T, Coman-Vlagea N, Della Vecchia A, Horeanga A, Papleux E, Vekemans M, Beukinga I, and Blairon L

Subjects
Adaptation, Physiological, COVID-19 Vaccines, Humans, RNA, Messenger, COVID-19
Abstract

Competing Interests: Declaration of Competing Interest The authors have no relevant competing interest to disclose in relation to this work.

Published
2022
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46. Homozygous GLI3 variants observed in three unrelated patients presenting with syndromic polydactyly.

Author

El Mouatani A, Van Winckel G, Zaafrane-Khachnaoui K, Whalen S, Achaiaa A, Kaltenbach S, Superti-Furga A, Vekemans M, Fodstad H, Giuliano F, and Attie-Bitach T

Subjects
Adult, Child, Female, Heterozygote, Homozygote, Humans, Infant, Newborn, Male, Pedigree, Polydactyly pathology, Genetic Predisposition to Disease, Nerve Tissue Proteins genetics, Polydactyly genetics, Zinc Finger Protein Gli3 genetics
Abstract

Polydactyly is a hallmark of GLI3 pathogenic variants, with Greig cephalopolysyndactyly syndrome and Pallister-Hall syndrome being the two main associated clinical presentations. Homozygous GLI3 variants are rare instances in the literature, and mendelian dominance is the accepted framework for GLI3-related diseases. Herein, we report three unrelated probands, presenting with polydactyly, and homozygous variants in the GLI3 gene. First, a 10-year-old girl, whose parents were first-degree cousins, presented with bilateral postaxial polydactyly of the hands, developmental delay and multiple malformations. Second, a male newborn, whose parents were first-degree cousins, presented with isolated bilateral postaxial polysyndactyly of the hands and the feet. Third, an adult male, whose parents were first-degree cousins, had bilateral mesoaxial polydactyly of the hands, with severe intellectual disability and multiple malformations. All three probands carried homozygous GLI3 variants. Strikingly, the parents also carried the child's variant, in the heterozygous state, without any clinical sign of GLI3 disease. Given the clinical presentation of our patients, the rarity and predicted high pathogenicity of the variants observed, and the absence of other pathogenic variants, we suggest that these GLI3 homozygous variants are causal. Moreover, the parents were heterozygous for the observed variants, but were clinically unremarkable, suggesting that these variants are hypomorphic alleles., (© 2021 Wiley Periodicals LLC.)

Published
2021
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47. Immunogenicity of mRNA-1273 COVID vaccine after 6 months surveillance in health care workers; a third dose is necessary.

Author

Tré-Hardy M, Cupaiolo R, Wilmet A, Antoine-Moussiaux T, Della Vecchia A, Horeanga A, Papleux E, Vekemans M, Beukinga I, and Blairon L

Subjects
2019-nCoV Vaccine mRNA-1273, Antibodies, Viral, Health Personnel, Humans, Immunogenicity, Vaccine, RNA, Messenger, SARS-CoV-2, COVID-19, COVID-19 Vaccines
Abstract

Objectives: Scarce data are currently available on the kinetics of antibodies after vaccination with mRNA vaccines as a whole and, with mRNA-1273, in particular. We report here an ad-interim analysis of data obtained after a 6-month follow-up in a cohort of healthcare workers (HCWs) who received the mRNA-1273 vaccine. These new data provide more insight into whether and in whom a 3rd dose could be necessary., Methods: Our study compared the anti-S antibody kinetics at 2 weeks (T1), 3 months (T3) and 6 months (T4) after the first injection, and 2 weeks after the second injection (T2). The 201 participating HCWs were stratified according to their initial serological status. The vaccine effectiveness was also assessed through a medical questionnaire., Results: We report here a marked and statistically significant antibody decrease (P < 0.05) between T3 and T4, especially in naïve vaccinees. The analysis of potential confounding factors or known risk factors for severe COVID-19 disease did not reveal any influence on the drop observed. Six-month after vaccination, only one, symptomatic, infection was reported in our cohort., Conclusions: In a supply-limited environment, our results plead for reserving the 3rd dose scheme, in the upcoming months, to seronegative individuals prior to vaccination, especially when the serological status is easily accessible., Competing Interests: Conflicts of Competing Interest The authors have no relevant competing interest to disclose in relation to this work., (Copyright © 2021. Published by Elsevier Ltd.)

Published
2021
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48. Reactogenicity, safety and antibody response, after one and two doses of mRNA-1273 in seronegative and seropositive healthcare workers.

Author

Tré-Hardy M, Cupaiolo R, Papleux E, Wilmet A, Horeanga A, Antoine-Moussiaux T, Della Vecchia A, Beukinga I, Vekemans M, and Blairon L

Subjects
Antibodies, Viral, Health Personnel, Humans, RNA, Messenger, Antibodies, Neutralizing, Antibody Formation
Abstract

Competing Interests: Declaration of Competing Interest The authors have no relevant competing interest to disclose in relation to this work.

Published
2021
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49. Intravascular lymphoma presenting with hypoxaemia, platypnoea and lactic acidosis.

Author

Englert P, Levy S, Vekemans M, and De Wilde V

Subjects
Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Dyspnea, Female, Humans, Hypoxia, Prednisone therapeutic use, Rituximab therapeutic use, Vincristine therapeutic use, Acidosis, Lactic diagnosis, Acidosis, Lactic drug therapy, Acidosis, Lactic etiology, Lymphoma, Large B-Cell, Diffuse complications, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy
Abstract

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive and rare type of diffuse extranodal B-cell lymphoma. Diagnosis and treatment are challenging and clinical presentation is variable. Physicians should be aware of this rare but life-threatening lymphoma without adenopathy and treatment should be promptly started. We describe the case of a 70-year-old woman who presented with general malaise, acute dyspnoea, platypnoea and lactic acidosis. Echocardiography revealed an extracardiac shunt, the cause of her orthodeoxia. The patient developed rapid liver failure and underwent liver biopsy. Anatomopathological findings suggested IVLBCL, non-germinal center type. She achieved complete remission after rituximab, cyclophosphamide, doxorubicin, vincristine, methylprednisolone chemotherapy but relapsed 1 year after initial presentation with multiple organ involvement. The patient's relapsed disease was treated with rituximab, iphosphamide, carboplatin, etoposide and she is still in complete remission 2 years later., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2021
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50. Women's Attitudes Toward Invasive and Noninvasive Testing When Facing a High Risk of Fetal Down Syndrome.

Author

Seror V, L'Haridon O, Bussières L, Malan V, Fries N, Vekemans M, Salomon LJ, and Ville Y

Subjects
Adult, Female, Health Knowledge, Attitudes, Practice, Humans, Pregnancy, Risk, Surveys and Questionnaires, Down Syndrome diagnosis, Down Syndrome psychology, Pregnancy Complications epidemiology, Pregnancy Complications psychology, Prenatal Diagnosis psychology
Abstract

Importance: Noninvasive prenatal testing (NIPT) using cell-free DNA in maternal blood is increasingly common compared with invasive testing (IT) in routine antenatal detection of Down syndrome (DS)., Objective: To assess attitudes and decision making in pregnant women facing a risk of fetal DS greater than 1 in 250 as established by combined first trimester screening at 11 to 14 weeks of gestation., Design, Setting, and Participants: Survey study in which data were collected from pregnant women at high risk of fetal DS participating in a randomized clinical trial. Data were collected from April 8, 2014, to April 7, 2016, in 57 prenatal diagnosis centers in France. Data were analyzed in 2018., Interventions: Data on attitudes were collected prior to offering randomization between NIPT and IT, whereas data on decision making and test results were collected as part of the clinical trial., Main Outcome and Measures: The primary outcome related to attitudes. A hierarchical cluster analysis was conducted to identify clusters with contrasting attitudes. Logistic regression analyses were used to identify factors associated with attitudes., Results: All 2436 consecutive women to whom the study was proposed (mean [SD] age, 36.3 [5.0] years) answered the questionnaire: 515 (21.1%) expressed preference toward IT with complete karyotyping, whereas 1843 (75.7%) favored NIPT with almost certain but limited information. Hierarchical cluster analysis yielded 4 different clusters that mainly differed in attitudes toward risk taking and extent of information seeking. Factors likely associated with attitudes driven by risk aversion were mostly age and religious beliefs (adjusted odds ratio [aOR], 1.03; 95% CI, 1.00-1.05; P = .03 and aOR, 1.62; 95% CI, 1.29-2.04; P < .001, respectively), whereas higher nuchal translucency measurements by ultrasonography were associated with attitudes driven by ambiguity aversion (aOR, 1.67; 95% CI, 1.27-2.20; P < .001). For attitudes involving both risk and ambiguity aversion at different extents, lower education was associated with highly valuing all possibilities of getting information on pregnancy, whereas higher education was associated with highly valuing information on fetal DS as a primary concern (aOR, 0.54; 95% CI, 0.44-0.67; P < .001 and aOR, 1.44; 95% CI, 1.20-1.74; P < .001, respectively). In all, decision making was in line with attitudes., Conclusions and Relevance: Aversion to risk of fetal loss related to IT and aversion to ambiguity generated by incomplete information from NIPT played a major role in shaping attitudes and decision making. Informed decision making should require pregnant women at high risk of DS to receive extensive information on targeted abnormalities by both tests.

Published
2019
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