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1. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion

Author

Toma, A, Kosmider, O, Chevret, S, Delaunay, J, Stamatoullas, A, Rose, C, Beyne-Rauzy, O, Banos, A, Guerci-Bresler, A, Wickenhauser, S, Caillot, D, Laribi, K, De Renzis, B, Bordessoule, D, Gardin, C, Slama, B, Sanhes, L, Gruson, B, Cony-Makhoul, P, Chouffi, B, Salanoubat, C, Benramdane, R, Legros, L, Wattel, E, Tertian, G, Bouabdallah, K, Guilhot, F, Taksin, A L, Cheze, S, Maloum, K, Nimuboma, S, Soussain, C, Isnard, F, Gyan, E, Petit, R, Lejeune, J, Sardnal, V, Renneville, A, Preudhomme, C, Fontenay, M, Fenaux, P, and Dreyfus, F

Published
2016
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2. Interferon Alpha and Cytosine Arabinoside in the Treatment of Chronic Myelogenous Leukemia

Author

Guilhot, F., Guerci, A., Michallet, M., Maloisel, F., Harousseau, J. L., Bouabdallah, R., Guyotat, D., Abgrall, J. F., Ifrah, N., Brière, J., Tertian, G., Bauters, F., Navarro, M., Morice, P., Christian, B., Vilque, J. M., Blanc, M., Hiddemann, W., editor, Büchner, T., editor, Wörmann, B., editor, Ritter, J., editor, Creutzig, U., editor, Keating, M., editor, and Plunkett, W., editor

Published
1998
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4. Toxic iron species in lower-risk myelodysplastic syndrome patients : course of disease and effects on outcome

Author

Hoeks, Marlijn, Bagguley, Tim, van Marrewijk, Corine, Smith, Alex, Bowen, David, Culligan, Dominic, Kolade, Seye, Symeonidis, Argiris, Garelius, Hege, Spanoudakis, Michail, Langemeijer, Saskia, Roelofs, Rian, Wiegerinck, Erwin, Tatic, Aurelia, Killick, Sally, Panagiotidis, Panagiotis, Stanca, Oana, Hellström-Lindberg, Eva, Cermak, Jaroslav, van der Klauw, Melanie, Wouters, Hanneke, van Kraaij, Marian, Blijlevens, Nicole, Swinkels, Dorine W., de Witte, Theo, Stauder, R., Walder, A., Pfeilstöcker, M., Schoenmetzler-Makrai, A., Burgstaller, S., Thaler, J., Mandac Rogulj, I., Krejci, M., Voglova, J., Rohon, P., Jonasova, A., Cermak, J., Mikulenkova, D., Hochova, I., Jensen, P. D., Holm, M. S., Kjeldsen, L., Dufva, I. H., Vestergaard, H., Re, D., Slama, B., Fenaux, P., Choufi, B., Cheze, S., Klepping, D., Salles, B., de Renzis, B., Willems, L., De Prost, D., Gutnecht, J., Courby, S., Siguret, V., Tertian, G., Pascal, L., Chaury, M., Wattel, E., Guerci, A., Legros, L., Itzykson, R., Ades, L., Isnard, F., Sanhes, L., Benramdane, R., Stamatoullas, A., Amé, S., Beyne-Rauzy, O., Gyan, E., Platzbecker, U., Badrakan, C., Germing, U., Lübbert, M., Schlenk, R., Kotsianidis, I., Tsatalas, C., Pappa, V., Galanopoulos, A., Michali, E., Panagiotidis, P., Viniou, N., Katsigiannis, A., Roussou, P., Terpos, E., Kostourou, A., Kartasis, Z., Pouli, A., Palla, K., Briasoulis, V., Hatzimichael, E., Vassilopoulos, G., Symeonidis, A., Kourakli, A., Zikos, P., Anagnostopoulos, A., Kotsopoulou, M., Megalakaki, K., Protopapa, M., Vlachaki, E., Konstantinidou, P., Stemer, G., Nemetz, A., Gotwin, U., Cohen, O., Koren, M., Levy, E., Greenbaum, U., Gino-Moor, S., Price, M., Ofran, Y., Winder, A., Goldshmidt, N., Elias, S., Sabag, R., Hellman, I., Ellis, M., Braester, A., Rosenbaum, H., Berdichevsky, S., Itzhaki, G., Wolaj, O., Yeganeh, S., Katz, O., Filanovsky, K., Dali, N., Mittelman, M., Malcovati, L., Fianchi, L., vd Loosdrecht, A., Matthijssen, V., Herbers, A., Pruijt, H., Aboosy, N., de Vries, F., Velders, G., Jacobs, E., Langemeijer, S., MacKenzie, M., Lensen, C., Kuijper, P., Madry, K., Camara, M., Almeida, A., Vulkan, G., Stanca Ciocan, O., Tatic, A., Savic, A., Pedro, C., Xicoy, B., Leiva, P., Munoz, J., Betes, V., Benavente, C., Lozano, M., Martinez, M., Iniesta, P., Bernal, T., Diez Campelo, M., Tormo, D., Andreu Lapiedra, R., Sanz, G., Hesse Sundin, E., Garelius, H., Karlsson, C., Antunovic, P., Jönsson, A., Brandefors, L., Nilsson, L., Kozlowski, P., Hellstrom-Lindberg, E., Grövdal, M., Larsson, K., Wallvik, J., Lorenz, F., Ejerblad, E., Culligan, D., Craddock, C., Kolade, S., Cahalin, P., Killick, S., Ackroyd, S., Wong, C., Warren, A., Drummond, M., Hall, C., Rothwell, K., Green, S., Ali, S., Bowen, D., Karakantza, M., Dennis, M., Jones, G., Parker, J., Bowen, A., Radia, R., Das-Gupta, E., Vyas, P., Nga, E., Creagh, D., Ashcroft, J., Mills, J., Bond, L., Life Course Epidemiology (LCE), and VU University medical center

Subjects
Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Iron Overload, Iron, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Ferroportin, Lower risk, Gastroenterology, Article, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], 03 medical and health sciences, 0302 clinical medicine, Hepcidin, Internal medicine, Humans, Medicine, Blood Transfusion, Prospective Studies, Aged, Soluble transferrin receptor, biology, business.industry, Transferrin saturation, Hematology, Middle Aged, Erythroferrone, Prognosis, 3. Good health, Survival Rate, Ferritin, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], 030104 developmental biology, Oncology, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, biology.protein, Erythropoiesis, Female, business, Myelodysplastic syndrome, Follow-Up Studies, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Red blood cell transfusions (RBCT) remain the cornerstone of supportive care in lower-risk myelodysplastic syndrome (LRMDS) [1]. Transfusion dependency in LRMDS patients is associated with inferior outcomes, mainly attributed to severe bone marrow failure [2]. However, iron toxicity, due to frequent RBCT or ineffective erythropoiesis, may be an additional negative prognostic factor [3,4,5,6]. Recently, much progress has been made in unraveling the iron metabolism. The peptide hormone hepcidin is the key regulator by inhibiting iron uptake through degradation of ferroportin, a cellular iron exporter [7]. Erythroferrone and GDF15, produced by erythroblasts, inhibit hepcidin production, which leads to increased uptake and cellular release of iron for the purpose of erythropoiesis [8]. The pathophysiology of iron metabolism in MDS is still not completely understood. Exceedingly high reactive oxygen species (ROS) levels are associated with iron toxicity, disease development, and progression in MDS patients [9,10,11,12]. Malondialdehyde (MDA), resulting from lipid peroxidation of polyunsaturated fatty acids, is a biomarker of oxidative stress [10, 12]. Currently, little is known about the prognostic impact of ROS in MDS patients. The aim of this study is twofold: (1) describe iron and oxidative stress parameters over time in LRMDS patients and (2) to assess their effect on overall and progression-free survival. The EUMDS registry prospectively collects observational data on newly diagnosed LRMDS patients from 148 centers in 16 countries in Europe and Israel as of January 2008. All patients provided informed consent. Clinical data were collected at baseline and at each six-monthly follow-up visit. Serum samples were collected prospectively at each visit from 256 patients included in six participating countries. Conventional iron parameters were measured with routine assays. We additionally analyzed hepcidin, growth differentiation factor 15 (GDF15), soluble transferrin receptor (sTfR), non-transferrin bound iron (NTBI), labile plasma iron (LPI), and MDA. Subjects were prospectively followed until death, loss to follow-up, or withdrawal of consent. All iron parameters were measured centrally at the department of Laboratory Medicine of the Radboudumc, Nijmegen, The Netherlands. Serum samples were collected just prior to transfusion in transfusion-dependent patients and stored at −80 °C. Details on the assays and reference ranges of hepcidin, GDF15, sTfR, NTBI, LPI, and MDA are provided in the supplement. The Spearman rank test was used to evaluate correlations between iron parameters. We stratified the results by transfusion dependency per visit and the presence of ring sideroblasts. When evaluating temporal changes in iron parameters, with linear quantile mixed models, we excluded patients from the timepoint they received iron chelation therapy. Overall survival (OS) was defined as the time from MDS diagnosis to death or, in case of progression-free survival, to date of progression or death; patients still alive at the end of follow-up were censored. Time-dependent Kaplan–Meier curves and cox proportional hazards models were used. In total, 256 consecutive patients, were included in this study. Over five six-monthly visits, 1040 samples were collected. Table 1 describes the patient characteristics. Most patients without ring sideroblasts were transfusion-independent at diagnosis (nonRS-TI; 55.9%), 18.8% with ring sideroblasts were transfusion-independent (RS-TI), 18.4% without ring sideroblasts were transfusion-dependent (nonRS-TD), and 7% with ring sideroblasts were transfusion-dependent patients (RS-TD). The median follow-up time was 6.6 years (95% CI 5.9–7.0). LPI was positively correlated with transferrin saturation (TSAT) (r = 0.15, p < 0.001, Fig. S1). LPI values increased exponentially at TSAT values above 80%. This effect was most pronounced in the transfusion-dependent groups, but also observed in the RS-TI group. MDA was weakly correlated with NTBI (r = 0.09, p = 0.069) and negatively correlated with hemoglobin level (r = −0.1, p = 0.033). GDF15 and hepcidin were negatively correlated in the RS-TI and nonRS-TD group and significantly negatively correlated in the RS-TD group (r = −0.34, p = 0.007, Fig. S2). Serum ferritin levels were elevated in all subgroups with a mean value of 858 µg/L at visit 5. The highest serum ferritin levels were observed in the RS-TD group (mean value at visit 5: 2092 µg/L, Table S1). Serum ferritin increased significantly per visit in the RS-TD group (beta 454.46 µg/L; 95% CI 334.65–574.27), but not in the other groups (Table S2). All subgroups, except for the nonRS-TI, had elevated TSAT levels. TSAT levels were most markedly increased in the RS-TD group with a mean TSAT of 88% at visit 5 (Table S1). In both transfusion-dependent groups the median increase per visit was significant (Table S2). LPI was elevated in the RS-TD group exclusively with a mean value of 0.59 µmol/L at visit 5 (Table S1). NTBI was elevated in all subgroups, with the highest values in the RS-TD group (Table S1). The increase in median NTBI level was significant in both transfusion-dependent groups (Table S2). Hepcidin levels were markedly elevated in the nonRS-TD group. Interestingly, hepcidin levels were lower in the RS-TD group, probably reflecting ineffective erythropoiesis, likewise supported by lower hepcidin/ferritin ratios in RS groups (Table S1). Median hepcidin levels increased over time in the transfusion-dependent subgroups only (Table S2). GDF15 levels, analyzed in the light of its potential role in hepcidin suppression, were increased in all subgroups (Table S1). The RS subgroups had higher GDF15 levels compared to the nonRS groups, reflecting increased erythropoiesis. Mean sTfR levels were within the reference range in all subgroups except for the RS-TI group, which showed elevated levels, reflecting...

Published
2021
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15. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion

Author

Toma, A, primary, Kosmider, O, additional, Chevret, S, additional, Delaunay, J, additional, Stamatoullas, A, additional, Rose, C, additional, Beyne-Rauzy, O, additional, Banos, A, additional, Guerci-Bresler, A, additional, Wickenhauser, S, additional, Caillot, D, additional, Laribi, K, additional, De Renzis, B, additional, Bordessoule, D, additional, Gardin, C, additional, Slama, B, additional, Sanhes, L, additional, Gruson, B, additional, Cony-Makhoul, P, additional, Chouffi, B, additional, Salanoubat, C, additional, Benramdane, R, additional, Legros, L, additional, Wattel, E, additional, Tertian, G, additional, Bouabdallah, K, additional, Guilhot, F, additional, Taksin, A L, additional, Cheze, S, additional, Maloum, K, additional, Nimuboma, S, additional, Soussain, C, additional, Isnard, F, additional, Gyan, E, additional, Petit, R, additional, Lejeune, J, additional, Sardnal, V, additional, Renneville, A, additional, Preudhomme, C, additional, Fontenay, M, additional, Fenaux, P, additional, and Dreyfus, F, additional

Published
2015
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17. Quality of life after successful treatment of early-stage Hodgkin's lymphoma: 10-year follow-up of the EORTC-GELA H8 randomised controlled trial.

Author

Heutte, N., Flechtner, H.H., Mounier, N., Mellink, W.A.M., Meerwaldt, J.H., Eghbali, H., Veer, M.B. van 't, Noordijk, E.M., Kluin-Nelemans, H.C., Lampka, E., Thomas, J., Lugtenburg, P.J., Viterbo, L., Carde, P., Hagenbeek, A., Maazen, R.W.M. van der, Smit, W.G., Brice, P., Marwijk-Kooy, M. van, Baars, J.W., Poortmans, P.M.P., Tirelli, U., Leeksma, O.C., Tomsic, R., Feugier, P., Salles, G., Gabarre, J., Kersten, M.J., Neste, E. van den, Creemers, G.J., Gaillard, I., Meijnders, P., Tertian, G., Reman, O., Muller, H.P., Troncy, J., Blanc, M., Schroyens, W., Voogt, P.J., Wijermans, P., Rieux, C., Ferme, C., Henry-Amar, M., Heutte, N., Flechtner, H.H., Mounier, N., Mellink, W.A.M., Meerwaldt, J.H., Eghbali, H., Veer, M.B. van 't, Noordijk, E.M., Kluin-Nelemans, H.C., Lampka, E., Thomas, J., Lugtenburg, P.J., Viterbo, L., Carde, P., Hagenbeek, A., Maazen, R.W.M. van der, Smit, W.G., Brice, P., Marwijk-Kooy, M. van, Baars, J.W., Poortmans, P.M.P., Tirelli, U., Leeksma, O.C., Tomsic, R., Feugier, P., Salles, G., Gabarre, J., Kersten, M.J., Neste, E. van den, Creemers, G.J., Gaillard, I., Meijnders, P., Tertian, G., Reman, O., Muller, H.P., Troncy, J., Blanc, M., Schroyens, W., Voogt, P.J., Wijermans, P., Rieux, C., Ferme, C., and Henry-Amar, M.

Abstract

Contains fulltext : 81805.pdf (publisher's version ) (Closed access), BACKGROUND: Little is known about the longitudinal course of health-related quality of life (HRQoL) in patients with Hodgkin's lymphoma during their post-treatment follow-up and re-adaptation to normal life. We report on the HRQoL of patients treated in the randomised H8 trial of the European Organisation for Research and Treatment of Cancer (EORTC) Lymphoma Group and the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). We aimed to assess HRQoL and fatigue following treatment, to analyse relations with treatment, and to identify factors that predict persistent fatigue. METHODS: Patients received HRQoL questionnaires at the end of primary therapy and during follow-up. The EORTC QLQ-C30 was used to assess HRQoL, and the Multidimensional Fatigue Inventory (MFI-20) was used to assess fatigue. Changes of mean HRQoL scores over time were analysed with mixed models. Multiple polytomic nominal logistic regression was done to identify independent baseline predictors of fatigue within MFI-20 dimensions. Analyses were done on an intention-to-treat basis. This study is registered with www.ClinicalTrials.gov, number NCT00379041. FINDINGS: 2666 assessments from 935 patients were analysed. Mean follow-up was 90 months (range 52-118). Age affected all functioning and symptom scores except emotional functioning, with younger age associated with higher functioning and lower severity of symptoms; improvement with time showed similar patterns between age groups. Women reported lower HRQoL and higher symptom scores than did men. Overall, 3.2% (14/439 for role functioning) to 9.7% (43/442 for social functioning) and 5.8% (29/498 for reduced motivation) to 9.9% (49/498 for general fatigue) of patients reported impairments of 10 points or more (on a 0-100 scale) in QLQ-C30 and MFI-20 scores, respectively, independent of age and sex. Emotional domains were more affected than physical ones. There was no relation between HRQoL outcome and type of treatment. Fatigue (MFI-20 scores) at the end

Published
2009

18. O-010 Prognostic factors of response to azacitidine (AZA) in low-risk MDS resistant to erythroid stimulating agents (ESA). The GFM Azaepo 08 study

Author

Gardin, C., primary, Thepot, S., additional, Beyne-Rauzy, O., additional, Benabdelali, R., additional, Prebet, T., additional, Park, S., additional, Stamatoulas, A., additional, Guerci-Bresler, A., additional, Cheze, S., additional, Tertian, G., additional, Choufi, B., additional, Legros, L., additional, Bastie, J.N., additional, Delaunay, J., additional, Chaury, M.P., additional, Wattel, E., additional, Dreyfus, F., additional, Preudhomme, C., additional, Vey, N., additional, and Fenaux, P., additional

Published
2013
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21. 291 Prognostic impact of JAK2V617F mutation in MDS: a matched case control study

Author

de Renzis, B., primary, de Mas, V., additional, Wattel, E., additional, Beyne-Rauzy, O., additional, Knoops, L., additional, Boyer, F., additional, Cabrespine, A., additional, Raynaud, S., additional, Rose, C., additional, Demory, J.L., additional, Nguyen-Khac, F., additional, Ades, L., additional, Tertian, G., additional, Ianotto, J.C., additional, Bordessoule, D., additional, Cahn, J.Y., additional, Fontenay, M., additional, Kiladjian, J.J., additional, and Fenaux, P., additional

Published
2011
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22. 162 A phase II study of decitabine in advanced chronic myelomonocytic leukemia (CMML)

Author

Braun, T., primary, Droin, N., additional, Itzykson, R., additional, de Renzis, B., additional, Dreyfus, F., additional, Laribi, K., additional, Boabdallah, K., additional, Charbonnier, A., additional, Cordonnier, C., additional, Lafon, I., additional, Recher, C., additional, Vey, N., additional, Bastie, J.-N., additional, Besançon, A., additional, Beyne-Rauzy, O., additional, Joly, B., additional, Jourdan, E., additional, Legros, L., additional, Marjanovic, Z., additional, Petitdidier, C., additional, Royer, B., additional, Sanhes, L., additional, Tertian, G., additional, Vaida, I., additional, Vallantin, X., additional, Vekhoff, A., additional, Milic, M., additional, Gardin, C., additional, Ades, L., additional, Fenaux, P., additional, and Solary, E., additional

Published
2011
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30. Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: final analysis of survival and toxicity in the Groupe d'Etude des Lymphomes Folliculaires 86 Trial.

Author

Solal-Céligny, P, primary, Lepage, E, additional, Brousse, N, additional, Tendler, C L, additional, Brice, P, additional, Haïoun, C, additional, Gabarre, J, additional, Pignon, B, additional, Tertian, G, additional, Bouabdallah, R, additional, Rossi, J F, additional, Doyen, C, additional, and Coiffier, B, additional

Published
1998
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42. Non Hodgkin’s lymphoma presenting as neutropenia related to an IgM monoclonal anti-i antibody.

Author

Cartron, J., Fior, R., Boué, F., Tertian, G., and Gane, P.

Abstract

A sixty-year old female was referred to the Internal Medicine Department for the treatment of a diffuse high-grade non Hodgkin’s lymphoma. She presented episodes of fever in a context of neutropenia (neutrophils 0.35 × 109/l from 1.6 × 109/l white blood cells). Hemoglobin level was 8.2 g/dl and platelets 132 × 1012/l. A monoclonal IgM-(kappa) protein (48 g/l) was detected in her serum. A direct antiglobulin test on the red cells proved positive with anti-C3d but not with anti-IgG antiglobulin, due to the presence of an IgM cold antibody with a serological anti-i specificity. The IgM antibody was found on the patient’s neutrophils as well as in her serum. This antibody recognized all neutrophils tested in conventional serological tests whatever the neutrophil phenotypes in systems NA, NB, and 5. It was demonstrated that it recognized the i antigen expressed on the neutrophils. These results suggest that a cold agglutinin anti-i might be responsible for neutropenia in some patients. [ABSTRACT FROM AUTHOR]

Published
1997
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43. Additional translocation (9;12)(p13;q24.1) in newly diagnosed chronic myeloid leukemia: complete cytogenetic remission after interferon therapy.

Author

Tertian, G., Avalos, M., Léonard, C., Lavergne, J., Misrahi, M., and Tchernia, G.

Abstract

We report the case of a patient with chronic phase CML who exhibited, in the same cells, beside the Philadelphia chromosome, an additional translocation between the other chromosome 9 and one of the chromosomes 12 [t(9;12)(p13;q24.1)]. Complete cytogenetic remission with disappearance of both karyotypic abnormalities was achieved after 18 months treatment with low dose (1.4 × 106 U/m2/day) recombinant alpha-interferon and has been sustained with maintenance therapy for 68+ months (actual follow-up). Clonality at diagnosis and recovery of polyclonal hematopoiesis in complete cytogenetic remission were demonstrated using the polymorphism at the human androgen receptor gene (Humara) locus on chromosome X. The role of the additional translocation in the response to low dose alpha-interferon therapy remains hypothetical. [ABSTRACT FROM AUTHOR]

Published
1997
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46. Prognostic factors of acute non lymphoblastic leukemia in children and adults. Results from two multicentric trials (705 patients)

Author

Castaigne S, Chevret S, Lepage E, François Guilhot, Fenaux P, Bordessoule D, Tilly H, Auzanneau G, Tertian G, and Guy H

Subjects
Adult, Adolescent, Remission Induction, Infant, Middle Aged, Prognosis, Survival Rate, Leukemia, Myeloid, Acute, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Humans, Prospective Studies, Child, Aged
Abstract

705 children and adults patients with de novo acute nonlymphoblastic leukemia were entered from 1981 to 1989 into 2 prospectives multicenter trials: 01AM81 and 01AM86. They received an intensive induction course with Rubidazone 200 mg/sqm/day x 4 days and cytosine arabinoside 200 mg/sqm/day x 7 days, then 3 consolidation courses at outpatients, and a maintenance treatment. Total duration of therapy was 3 years. The overall complete remission rate was 80%. The median overall survival time was 19 months and the 5-year survival rate is 26%. The median remission duration for the 568 remitters was 18 months and the 5-year first remission rate is 30%. Prognostic factors for the remission rate were age, initial leukocytosis, FAB subtype. Prognostic factors for remission duration were the delay until CR, initial leukocytosis and karyotype.

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