49 results on '"J J Kiladjian"'
Search Results
2. S195: MOMENTUM: PHASE 3 RANDOMIZED STUDY OF MOMELOTINIB (MMB) VERSUS DANAZOL (DAN) IN SYMPTOMATIC AND ANEMIC MYELOFIBROSIS (MF) PATIENTS PREVIOUSLY TREATED WITH A JAK INHIBITOR
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S. Verstovsek, A. Vannucchi, A. Gerds, H. K. Al-Ali, D. Lavie, A. Kuykendall, S. Grosicki, A. Iurlo, Y. T. Goh, M. Lazaroiu, M. Egyed, M. L. Fox, D. McLornan, A. Perkins, S.-S. Yoon, V. Gupta, J.-J. Kiladjian, R. Donahue, J. Kawashima, and R. Mesa
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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3. S193: GENOMIC AND FUNCTIONAL IMPACT OF TP53 INACTIVATION IN JAK2V617F MYELOPROLIFERATIVE NEOPLASMS: A TRANSGENIC MOUSE MODEL APPROACH.
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P. GOU, D. LIU, E. Lauret, N. Maslah, V. Montcuquet, V. meignin, J.-J. Kiladjian, B. Cassinat, and S. Giraudier
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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4. S198: BET INHIBITOR PELABRESIB (CPI-0610) COMBINED WITH RUXOLITINIB IN PATIENTS WITH MYELOFIBROSIS — JAK INHIBITOR-NAÏVE OR WITH SUBOPTIMAL RESPONSE TO RUXOLITINIB — PRELIMINARY DATA FROM THE MANIFEST STUDY
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J. Mascarenhas, M. Kremyanskaya, A. Patriarca, C. Harrison, P. Bose, R. K. Rampal, F Palandri, T. Devos, F. Passamonti, G. Hobbs, M. Talpaz, A. Vannucchi, J.-J. Kiladjian, S. Verstovsek, R. Hoffman, M. E. Salama, D. Chen, P. Taverna, A. Chang, G. Colak, S. Klein, and V. Gupta
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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5. P995: MYELOID NEOPLASMS-ASSOCIATED GENE VARIANTS IN 639 PATIENTS WITH POST-POLYCYTHEMIA VERA AND POST-ESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS: AN ANALYSIS OF THE MYSEC COHORT
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B. Mora, P. Guglielmelli, A. Kuykendall, M. Maffioli, G. Rotunno, R. S. Komrokji, F. Palandri, J.-J. Kiladjian, A. Iurlo, G. Auteri, D. Cattaneo, V. De Stefano, S. Salmoiraghi, T. Devos, F. Cervantes, M. Merli, A. Campagna, G. Benevolo, M. Brociner, F. Albano, J. Gotlib, M. Caramella, M. Ruggeri, D. M. Ross, F. Orsini, C. Pessina, I. Colugnat, F. Pallotti, T. Barbui, L. Bertù, M. G. Della Porta, A. M. Vannucchi, and F. Passamonti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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6. P1009: PREDICTORS OF HOSPITALIZATION AND SEVERE OUTCOMES IN PATIENTS WITH MPN AND COVID-19
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T. Barbui, A. Carobbio, A. Masciulli, A. Iurlo, M. A. Sobas, E. M. Elli, E. Rumi, V. De Stefano, F. Lunghi, M. Marchetti, R. Daffini, M. Gasior Kabat, B. Cuevas, M. L. Fox, M. M. Andrade Campos, F. Palandri, P. Guglielmelli, G. Benevolo, C. Harrison, M. A. Foncillas, M. Bonifacio, A. Alvarez-Larran, J.-J. Kiladjian, E. Bolanos Calderon, A. Patriarca, K. S. Quiroz Cervantes, M. Griesshammer, V. Garcia-Gutierrez, A. Marin Sanchez, E. Magro Mazo, M. Ruggeri, J. C. Hernandez-Boluda, S. Osorio, G. Carreno-Tarragona, M. Sagues Serrano, R. Kusec, B. Navas Elorza, A. Angona, B. Xicoy Cirici, E. Lopez Abadia, S. Koschmieder, E. Cichocka, A. Kulikowska de Nałęcz, M. Bellini, D. Cattaneo, C. Bucelli, F. Cavalca, O. Borsani, S. Betti, N. Curto-Garcia, S. Carbonell, L. Benajiba, A. Rambaldi, and A. M. Vannucchi
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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7. P980: JAK2V617F-DEPENDENT DOWN REGULATION OF SHP1 EXPRESSION PARTICIPATES IN THE SELECTION OF MPN CELLS IN THE PRESENCE OF TGFΒ
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C. Aoun, N. Salomao, N. Maslah, S. Awan Toor, G. Letort, P. Gou, J.-J. Kiladjian, S. Giraudier, and B. Cassinat
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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8. P1069: RETROSPECTIVE COMPARISON OF PATIENT OUTCOMES ON PACRITINIB VERSUS RUXOLITINIB IN PATIENTS WITH MYELOFIBROSIS AND THROMBOCYTOPENIA
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C. Harrison, P. Bose, R. Mesa, A. Gerds, S. Oh, J.-J. Kiladjian, V. García-Gutierrez, A. Vannucchi, C. Scheid, M. Sobas, S. Verstovsek, S. Buckley, K. Roman-Torres, and J. Mascarenhas
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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9. P1029: MATCHING-ADJUSTED INDIRECT COMPARISON (MAIC) OF PELABRESIB (CPI-0610) IN COMBINATION WITH RUXOLITINIB VS RUXOLITINIB OR FEDRATINIB MONOTHERAPY IN PATIENTS WITH INTERMEDIATE OR HIGH-RISK MYELOFIBROSIS
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V. Gupta, J. Mascarenhas, M. Kremyanskaya, R. K. Rampal, M. Talpaz, J.-J. Kiladjian, A. Vannucchi, S. Verstovsek, G. Colak, D. Dey, and C. Harrison
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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10. P1050: THROMBOCYTOPENIC MYELOFIBROSIS (MF) PATIENTS PREVIOUSLY TREATED WITH A JAK INHIBITOR IN A PHASE 3 RANDOMIZED STUDY OF MOMELOTINIB (MMB) VERSUS DANAZOL (DAN) [MOMENTUM]
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A. Vannucchi, R. Mesa, A. Gerds, H. K. Al-Ali, D. Lavie, A. Kuykendall, S. Grosicki, A. Iurlo, Y. T. Goh, M. Lazaroiu, M. Egyed, M. L. Fox, D. McLornan, A. Perkins, S.-S. Yoon, V. Gupta, J.-J. Kiladjian, R. Donahue, J. Kawashima, and S. Verstovsek
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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11. P1042: SAFETY AND TOLERABILITY RESULTS FROM THE PHASE 3B FREEDOM TRIAL OF FEDRATINIB (FEDR), AN ORAL, SELECTIVE JAK2 INHIBITOR, IN PATIENTS WITH MYELOFIBROSIS (MF) PREVIOUSLY TREATED WITH RUXOLITINIB (RUX)
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V. Gupta, A. Yacoub, S. Verstovsek, R. A. Mesa, C. N. Harrison, G. Barosi, J.-J. Kiladjian, H. J. Deeg, S. Fazal, L. Foltz, R. J. Mattison, C. B. Miller, V. Parameswaran, C. Hernandez, J. Zhang, and M. Talpaz
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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12. P1041: IMPACT OF FEDRATINIB ON SPLEEN VOLUME AND MYELOFIBROSIS SYMPTOMS IN PATIENTS WITH SUBSTANTIAL SPLENOMEGALY: POST HOC ANALYSES FROM THE JAKARTA AND JAKARTA2 TRIALS
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J.-J. Kiladjian, A. Tefferi, F. Passamonti, A. Vannucchi, M. Talpaz, F. Cervantes, C. N. Harrison, R. A. Mesa, J. Mascarenhas, N. Schaap, S. Verstovsek, T. Devos, S. Rose, J. Zhang, O. Sy, and A. Pardanani
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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13. P1037: DOES EARLY INTERVENTION IN MYELOFIBROSIS IMPACT OUTCOMES? A POOLED ANALYSIS OF THE COMFORT I AND II STUDIES
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C. Harrison, J.-J. Kiladjian, A. M. Vannucchi, R. A. Mesa, R. M. Scherber, J. Hamer-Maansson, and S. Verstovsek
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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14. P1030: MANIFEST-2, A GLOBAL, PHASE 3, RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROL STUDY OF PELABRESIB (CPI-0610) AND RUXOLITINIB VS PLACEBO AND RUXOLITINIB IN JAK INHIBITOR-NAÏVE MYELOFIBROSIS PATIENTS
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C. Harrison, R. K. Rampal, V. Gupta, S. Verstovsek, M. Talpaz, J.-J. Kiladjian, R. Mesa, A. Kuykendall, A. Vannucchi, F. Palandri, S. Grosicki, T. Devos, E. Jourdan, M. J. Wondergem, H. K. Al-Ali, V. Buxhofer-Ausch, A. Alvarez-Larrán, S. Akhani, R. Muñoz-Carerras, Y. Sheykin, G. Colak, M. Harris, and J. Mascarenhas
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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15. P1048: MYF3001: A RANDOMIZED OPEN LABEL, PHASE 3 STUDY TO EVALUATE IMETELSTAT VERSUS BEST AVAILABLE THERAPY IN PATIENTS WITH INTERMEDIATE-2 OR HIGH-RISK MYELOFIBROSIS REFRACTORY TO JANUS KINASE INHIBITOR
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J. Mascarenhas, C. N. Harrison, J.-J. Kiladjian, R. S. Komrokji, S. Koschmieder, A. M. Vannucchi, T. Berry, D. Redding, L. Sherman, S. Dougherty, L. Peng, L. Sun, F. Huang, Y. Wan, F. M. Feller, A. Rizo, and S. Verstovsek
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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16. Access to early-phase clinical trials in older patients with cancer in France: the EGALICAN-2 study
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C, Baldini, E, Charton, E, Schultz, L, Auroy, A, Italiano, M, Robert, E, Coquan, N, Isambert, P, Moreau, S, Le Gouill, C, Le Tourneau, Z, Ghrieb, J J, Kiladjian, J P, Delord, C Gomez, Roca, N, Vey, F, Barlesi, T, Lesimple, N, Penel, J C, Soria, C, Massard, and S, Besle
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Clinical Trials as Topic ,Cancer Research ,Oncology ,Incidence ,Neoplasms ,Humans ,France ,Aged - Abstract
Access to clinical trials and especially early-phase trials (ECT) is an important issue in geriatric oncology. As cancer can be considered an age-related disease because the incidence of most cancers increases with age, new drugs should also be evaluated in older patients to assess their safety and efficacy. The EGALICAN-2 study was primarily designed to identify social and/or regional inequalities regarding access to ECT. We focused on the factors of inequalities in access to ECT in older patients.During a 1-year period (2015-2016), a survey was conducted in 11 early-phase units certified by the French National Cancer Institute.A total of 1319 patients were included in the analyses: 1086 patients (82.3%) were70 years and 233 patients (17.7%) were70 years. The most common tumor types at referral in older patients were gastrointestinal (19.3%), hematological (19.3%), and thoracic tumors (18.0%). Most patients referred to the phase I unit had signed informed consent and the rate was similar across age (92.7% in younger patients versus 90.6% in older patients; P = 0.266). The rate of screening failure was also similar across age (28.5% in younger patients versus 24.3% in older patients; P = 0.219). Finally, in older patients, univariate analyses showed that initial care received in the hospital having a phase I unit was statistically associated with first study drug administration (odds ratio 0.49, 90% confidence interval 0.27-0.88; P = 0.045).Older patients are underrepresented in early clinical trials with 17.7% of patients aged ≥70 years compared with the number of new cases of cancer in France (50%). However, when invited to participate, older patients were prone to sign informed consent.
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- 2022
17. Supplement to: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis.
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C, Harrison, J-J, Kiladjian, and Al-Ali, H K
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- 2012
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18. Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both
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Hans Carl Hasselbalch, Tiziano Barbui, A. Maria Vannucchi, Tariq I. Mughal, Steffen Koschmieder, Heike L. Pahl, Richard T. Silver, G Barosi, Georg Jeryczynski, Jonas S. Jutzi, Francisco Cervantes, J J Kiladjian, Heinz Gisslinger, Peter Valent, and Ruediger Hehlmann
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Anti-Inflammatory Agents ,Inflammation ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Myeloproliferative Disorders ,Neoplasms ,Internal medicine ,Humans ,Medicine ,Progenitor cell ,Hematology ,business.industry ,medicine.disease ,Clone Cells ,Leukemia ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,medicine.symptom ,Stem cell ,business ,Clone (B-cell biology) - Abstract
The Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal disorders involving hematopoietic stem and progenitor cells and are associated with myeloproliferation, splenomegaly and constitutional symptoms. Similar signs and symptoms can also be found in patients with chronic inflammatory diseases, and inflammatory processes have been found to play an important role in the pathogenesis and progression of MPNs. Signal transduction pathways involving JAK1, JAK2, STAT3 and STAT5 are causally involved in driving both the malignant cells and the inflammatory process. Moreover, anti-inflammatory and immune-modulating drugs have been used successfully in the treatment of MPNs. However, to date, many unresoved issues remain. These include the role of somatic mutations that are present in addition to JAK2V617F, CALR and MPL W515 mutations, the interdependency of malignant and nonmalignant cells and the means to eradicate MPN-initiating and -maintaining cells. It is imperative for successful therapeutic approaches to define whether the malignant clone or the inflammatory cells or both should be targeted. The present review will cover three aspects of the role of inflammation in MPNs: inflammatory states as important differential diagnoses in cases of suspected MPN (that is, in the absence of a clonal marker), the role of inflammation in MPN pathogenesis and progression and the use of anti-inflammatory drugs for MPNs. The findings emphasize the need to separate the inflammatory processes from the malignancy in order to improve our understanding of the pathogenesis, diagnosis and treatment of patients with Philadelphia-negative MPNs.
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- 2016
19. Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone
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Bruno Cassinat, J J Kiladjian, and Stéphane Giraudier
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Clone (cell biology) ,Alpha interferon ,Antiviral Agents ,03 medical and health sciences ,0302 clinical medicine ,Myeloproliferative Disorders ,Internal medicine ,medicine ,Humans ,Hematology ,biology ,Interferon-alpha ,medicine.disease ,Lymphoma ,Leukemia ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Cancer research ,Stem cell ,Calreticulin - Abstract
Interferon alpha (IFN-α) has been used for over 30 years to treat myeloproliferative neoplasms (MPNs). IFN-α was shown to induce clinical, hematological, molecular and histopathological responses in small clinical studies. Such combined efficacy has never been achieved with any other drug to date in such a significant proportion of patients. However, toxicity remains a limitation to its broader use despite the development of pegylated forms with better tolerance. Several on going phase 3 studies of peg- IFN-α versus hydroxyurea will help to define its exact place in MPN management. IFN-α efficacy is likely the consequence of a broad range of biological properties, including enhancement of immune response, direct effects on malignant cells and ability to cycle dormant malignant stem cells. However, comprehensive elucidation of its mechanism of action is still lacking. Sustained clinical, molecular and morphological responses after IFN-α discontinuation raised the hope that this drug could eradicate MPN. There is now consistent evidence showing that IFN-α is able to eliminate malignant clones harboring JAK2V617F or Calreticulin mutations. However, the molecular complexity of these diseases could hamper IFN-α efficacy, as the presence of additional non-driver mutations, like in the TET2 gene, could be associated with resistance to IFN-α. Therefore, combined therapy with another targeted agent could be required to eradicate MPN, and the best IFN-α companion for achieving this challenge remains to be determined.
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- 2015
20. PS1457 MAINTENANCE OF RESPONSE IN LONG-TERM TREATMENT WITH ROPEGINTERFERON ALFA-2B (BESREMI®) VS. HYDROXYUREA IN POLYCYTHEMIA VERA PATIENTS (PROUD/CONTINUATION-PV PHASE III TRIALS)
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M. Egyed, L. Gercheva-Kyuchukova, Hans Carl Hasselbalch, D. Krochmalczyk, B. Grohmann-Izay, L. Sivcheva, P. Georgiev, K. Krejcy, J.-J. Kiladjian, A. illes, P. Dulicek, G. Maurer, J. Mayer, R. Kralovics, V. Yablokova, C. Klade, H. Pylypenko, V. Rossiev, and H. Gisslinger
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medicine.medical_specialty ,Long term treatment ,Polycythemia vera ,Phase iii trials ,business.industry ,Internal medicine ,medicine ,Hematology ,medicine.disease ,business ,Gastroenterology - Published
- 2019
21. PS1459 FEDRATINIB IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASM (MPN)-ASSOCIATED MYELOFIBROSIS (MF) PREVIOUSLY TREATED WITH RUXOLITINIB (RUX): A REANALYSIS OF THE PHASE 2 JAKARTA-2 STUDY
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Ruben A. Mesa, Srdan Verstovsek, N. Schaap, S. Rose, C. Harrison, Francesco Passamonti, Richard T. Silver, M. Li, Sonja Zweegman, T. Gerike, Harry C. Schouten, M. Talpaz, J.-J. Kiladjian, Alessandro M. Vannucchi, C. Brownstein, and E. Jourdan
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Oncology ,medicine.medical_specialty ,Ruxolitinib ,business.industry ,Hematology ,medicine.disease ,Fedratinib ,Internal medicine ,medicine ,In patient ,business ,Myelofibrosis ,Previously treated ,Myeloproliferative neoplasm ,medicine.drug - Published
- 2019
22. The role of LNK/SH2B3 genetic alterations in myeloproliferative neoplasms and other hematological disorders
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Laura Velazquez, Emmanuelle Verger, J J Kiladjian, Nabih Maslah, Bruno Cassinat, and INSERM U1197
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0301 basic medicine ,Cancer Research ,Context (language use) ,Polycythemia ,Gene mutation ,Biology ,medicine.disease_cause ,Germline ,03 medical and health sciences ,medicine ,Animals ,Humans ,Epigenetics ,Gene ,ComputingMilieux_MISCELLANEOUS ,Adaptor Proteins, Signal Transducing ,Regulation of gene expression ,Genetics ,Mutation ,Myeloproliferative Disorders ,Intracellular Signaling Peptides and Proteins ,Proteins ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Janus Kinase 2 ,Hematologic Diseases ,Phenotype ,3. Good health ,030104 developmental biology ,Oncology ,Hematologic Neoplasms - Abstract
Malignant hematological diseases are mainly because of the occurrence of molecular abnormalities leading to the deregulation of signaling pathways essential for precise cell behavior. High-resolution genome analysis using microarray and large-scale sequencing have helped identify several important acquired gene mutations that are responsible for such signaling deregulations across different hematological malignancies. In particular, the genetic landscape of classical myeloproliferative neoplasms (MPNs) has been in large part completed with the identification of driver mutations (targeting the cytokine receptor/Janus-activated kinase 2 (JAK2) pathway) that determine MPN phenotype, as well as additional mutations mainly affecting the regulation of gene expression (epigenetics or splicing regulators) and signaling. At present, most efforts concentrate in understanding how all these genetic alterations intertwine together to influence disease evolution and/or dictate clinical phenotype in order to use them to personalize diagnostic and clinical care. However, it is now evident that factors other than somatic mutations also play an important role in MPN disease initiation and progression, among which germline predisposition (single-nucleotide polymorphisms and haplotypes) may strongly influence the occurrence of MPNs. In this context, the LNK inhibitory adaptor protein encoded by the LNK/SH2B adaptor protein 3 (SH2B3) gene is the target of several genetic variations, acquired or inherited in MPNs, lymphoid leukemia and nonmalignant hematological diseases, underlying its importance in these pathological processes. As LNK adaptor is a key regulator of normal hematopoiesis, understanding the consequences of LNK variants on its protein functions and on driver or other mutations could be helpful to correlate genotype and phenotype of patients and to develop therapeutic strategies to target this molecule. In this review we summarize the current knowledge of LNK function in normal hematopoiesis, the different SH2B3 mutations reported to date and discuss how these genetic variations may influence the development of hematological malignancies.
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- 2017
23. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis
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Marianna Caramella, Giulia Benevolo, Margherita Maffioli, Francesca Palandri, Paola Guglielmelli, Domenica Caramazza, Francesco Albano, Rami S. Komrokji, T Barbui, V. De Stefano, J J Kiladjian, Toni Giorgino, Marco Ruggeri, Jason Gotlib, Richard T. Silver, Rosario Casalone, Timothy Devos, Alessandro M. Vannucchi, Mario Cazzola, Barbara Mora, Francesco Passamonti, Elisa Rumi, Giada Rotunno, Daniela Pietra, Francisco Cervantes, Michele Merli, and Alessandro Rambaldi
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Cancer Research ,Constitutional symptoms ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Polycythemia vera ,Hematology ,Anesthesiology and Pain Medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Prognostic Model ,Cancer Research, Secondary Myelofibrosis, Prognostic Model ,Myelofibrosis ,Polycythemia Vera ,Survival analysis ,Aged ,Aged, 80 and over ,model ,business.industry ,Essential thrombocythemia ,hematology ,Secondary Myelofibrosis ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Settore MED/15 - MALATTIE DEL SANGUE ,Oncology ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Cohort ,Mutation ,Prognostic model ,Female ,business ,prognostic ,Biomarkers ,030215 immunology ,Follow-Up Studies ,Thrombocythemia, Essential - Abstract
Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms with variable risk of evolution into post-PV and post-ET myelofibrosis, from now on referred to as secondary myelofibrosis (SMF). No specific tools have been defined for risk stratification in SMF. To develop a prognostic model for predicting survival, we studied 685 JAK2, CALR, and MPL annotated patients with SMF. Median survival of the whole cohort was 9.3 years (95% CI: 8-not reached-NR-). Through penalized Cox regressions we identified negative predictors of survival and according to beta risk coefficients we assigned 2 points to hemoglobin level
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- 2017
24. Driver mutations' effect in secondary myelofibrosis: An international multicenter study based on 781 patients
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Jason Gotlib, Alessandro M. Vannucchi, Elisa Rumi, Lisa Pieri, F Cervantes, Margherita Maffioli, M Ruggeri, Toni Giorgino, V. De Stefano, Paola Guglielmelli, T Devos, R Casalone, Barbara Mora, T Barbui, Marianna Caramella, G Benevolo, Richard T. Silver, Francesco Albano, Francesca Palandri, Rami S. Komrokji, Francesco Passamonti, Domenica Caramazza, Mario Cazzola, Daniela Pietra, Michele Merli, J J Kiladjian, and Alessandro Rambaldi
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Adult ,Oncology ,medicine.medical_specialty ,Cancer Research ,health care facilities, manpower, and services ,education ,03 medical and health sciences ,0302 clinical medicine ,Hematology ,Anesthesiology and Pain Medicine ,Internal medicine ,Secondary Myelofibrosis ,medicine ,Humans ,Intensive care medicine ,health care economics and organizations ,Aged ,Aged, 80 and over ,business.industry ,Janus Kinase 2 ,Middle Aged ,Settore MED/15 - MALATTIE DEL SANGUE ,Multicenter study ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Mutation ,business ,human activities ,030215 immunology - Abstract
Driver mutations’ effect in secondary myelofibrosis: an international multicenter study based on 781 patients
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- 2017
25. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence
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Francesco Passamonti, Alessandro M. Vannucchi, Robert Peter Gale, Vincent Ribrag, D Reiser, Qian Jiang, Heinz Gisslinger, A Tefferi, Haifa Kathrin Al-Ali, Mary Frances McMullin, G Barosi, Timothy Devos, J Zhong, Ruben A. Mesa, Gary J. Schiller, Daobin Zhou, and J. J. Kiladjian
- Subjects
Male ,Cancer Research ,Workflow ,Myeloproliferative disease ,0302 clinical medicine ,Hematology ,Anesthesiology and Pain Medicine ,Biological therapy ,Aged, 80 and over ,education.field_of_study ,Middle Aged ,Thalidomide ,Phenotype ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Randomized controlled trials ,Original Article ,Female ,Erratum ,Clinical pharmacology ,Erythrocyte Transfusion ,medicine.drug ,Adult ,medicine.medical_specialty ,Randomization ,Population ,Placebo ,03 medical and health sciences ,Internal medicine ,medicine ,Journal Article ,Humans ,Immunologic Factors ,education ,Myeloproliferative neoplasm ,Aged ,Myeloproliferative Disorders ,business.industry ,Odds ratio ,Pomalidomide ,medicine.disease ,Surgery ,Primary Myelofibrosis ,business ,Biomarkers ,030215 immunology - Abstract
RBC-transfusion dependence is common in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. The objective of this study was to determine the rates of RBC-transfusion independence after therapy with pomalidomide vs placebo in persons with MPN-associated myelofibrosis and RBC-transfusion dependence. Two hundred and fifty-two subjects (intent-to-treat (ITT) population) including 229 subjects confirmed by central review (modified ITT population) were randomly assigned (2:1) to pomalidomide or placebo. Trialists and subjects were blinded to treatment allocation. Primary end point was proportion of subjects achieving RBC-transfusion independence within 6 months. One hundred and fifty-two subjects received pomalidomide and 77 placebo. Response rates were 16% (95% confidence interval (CI), 11, 23%) vs 16% (8, 26%; P=0.87). Response in the pomalidomide cohort was associated with ⩽4 U RBC/28 days (odds ratio (OR)=3.1; 0.9, 11.1), age ⩽65 (OR=2.3; 0.9, 5.5) and type of MPN-associated myelofibrosis (OR=2.6; 0.7, 9.5). Responses in the placebo cohort were associated with ⩽4 U RBC/28 days (OR=8.6; 0.9, 82.3), white blood cell at randomization >25 × 109/l (OR=4.9; 0.8, 28.9) and interval from diagnosis to randomization >2 years (OR=4.9; 1.1, 21.9). Pomalidomide was associated with increased rates of oedema and neutropenia but these adverse effects were manageable. Pomalidomide and placebo had similar RBC-transfusion-independence response rates in persons with MPN-associated RBC-transfusion dependence.
- Published
- 2016
26. PS1458 RISK FACTORS AND OUTCOME OF ACUTE MYELOID LEUKEMIA SECONDARY TO POST-POLYCYTHEMIA VERA AND POST-ESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS: AN ANALYSIS OF THE MYSEC COHORT
- Author
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Jason Gotlib, Rami S. Komrokji, Timothy Devos, Daniela Pietra, Giada Rotunno, V. De Stefano, Francisco Cervantes, T Barbui, J J Kiladjian, Chiara Cavalloni, Daniela Barraco, Giulia Benevolo, Paola Guglielmelli, Elisa Rumi, A. Iurlo, Francesco Albano, A. Vannucchi, Lorenza Bertù, Margherita Maffioli, Marianna Caramella, Mario Cazzola, Francesco Passamonti, Barbara Mora, Francesca Palandri, Marco Ruggeri, Alessandro Rambaldi, and Richard T. Silver
- Subjects
Oncology ,medicine.medical_specialty ,Polycythemia vera ,Post-Essential Thrombocythemia Myelofibrosis ,business.industry ,Internal medicine ,Cohort ,medicine ,Myeloid leukemia ,Hematology ,business ,medicine.disease - Published
- 2019
27. S1610 MASKED POLYCYTHEMIA VERA: ANALYSIS OF A SINGLE CENTER SERIES OF 2480 RED CELL MASSES
- Author
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C Chomienne, M H Schlageter, Juliette Soret-Dulphy, N. Maslah, J.-J. Kiladjian, L. Vercellino, C. Belkhodja, B. Cassinat, Christine Dosquet, and S. Giraudier
- Subjects
Red Cell Masses ,Pathology ,medicine.medical_specialty ,Polycythemia vera ,Chemistry ,medicine ,Hematology ,Single Center ,medicine.disease - Published
- 2019
28. PS1472 CURRENT PRACTICE IN THE MANAGEMENT OF ESSENTIAL THROMBOCYTEMIA AND POLYCYTHEMIA VERA: A SURVEY FROM THE FRENCH INTERGROUP OF MYELOPROLIFERATIVE NEOPLASMS (FIM) AMONG 120 HEMATOLOGISTS AND INTERNISTS
- Author
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L. Roy, P. Cony-Makhoul, P. Lionne-Huyghe, J.-J. Kiladjian, E. Lippert, S. Giraudier, B. Dupriez, G. Fouquet, V. Ugo, and M. Wémeau
- Subjects
medicine.medical_specialty ,Polycythemia vera ,Current practice ,business.industry ,medicine ,Essential Thrombocytemia ,Hematology ,medicine.disease ,business ,Intensive care medicine - Published
- 2019
29. Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations
- Author
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Ruediger Hehlmann, Mary Frances McMullin, Monia Marchetti, Francesco Passamonti, Francisco Cervantes, Gunnar Birgegård, J. J. Kiladjian, Martin Griesshammer, G Barosi, T Barbui, Alessandro M. Vannucchi, Christine J. Harrison, and N Kröger
- Subjects
medicine.medical_specialty ,Ruxolitinib ,Cancer Research ,Evidence-based practice ,Hemorrhage ,Comorbidity ,Infections ,law.invention ,03 medical and health sciences ,European LeukemiaNet ,0302 clinical medicine ,Randomized controlled trial ,Hematology ,Anesthesiology and Pain Medicine ,law ,Internal medicine ,Hypertension, Portal ,Nitriles ,medicine ,Humans ,Molecular Targeted Therapy ,Myelofibrosis ,Protein Kinase Inhibitors ,business.industry ,Janus Kinase 1 ,Janus Kinase 2 ,medicine.disease ,Phenotype ,Pyrimidines ,Treatment Outcome ,Oncology ,Primary Myelofibrosis ,International Prognostic Scoring System ,030220 oncology & carcinogenesis ,Splenomegaly ,Physical therapy ,Pyrazoles ,business ,030215 immunology ,medicine.drug - Abstract
Ruxolitinib is an oral Janus-activated kinase 1 (JAK1)/JAK2 inhibitor approved for the treatment of patients with myelofibrosis based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of the three clinical outcomes: (a) splenomegaly, (b) disease-related symptoms, and (c) survival. Ruxolitinib was strongly recommended for improving symptomatic or severe (>15 cm below the costal margin) splenomegaly in patients with an International Prognostic Scoring System (IPSS)/dynamic IPSS risk intermediate 2 or high. Ruxolitinib was also strongly recommended for improving systemic symptoms in patients with an MPN10 score >44, refractory severe itching, unintended weight loss not attributable to other causes or unexplained fever. Because of weak evidence, the panel does not recommend ruxolitinib therapy for improving survival. Also, the recommendations given above do not necessarily apply to patients who are candidates for allogeneic stem cell transplant.
- Published
- 2016
30. Is there consensus on consensus?
- Author
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J J Kiladjian and Robert Peter Gale
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Hematology ,Consensus ,business.industry ,medicine.disease ,Lymphoma ,Fusion gene ,03 medical and health sciences ,Haematopoiesis ,Leukemia ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Internal medicine ,Immunology ,Cancer research ,Medicine ,Humans ,Stem cell ,business - Published
- 2016
31. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
- Author
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A M, Vannucchi, T, Barbui, F, Cervantes, C, Harrison, J-J, Kiladjian, N, Kröger, J, Thiele, C, Buske, and Svetlana, Jezdic
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,Philadelphia Chromosome Negative ,Myeloproliferative disease ,Hematology ,Guideline ,University hospital ,Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ,Transplantation ,Clinical Practice ,Oncology ,Diagnosis treatment ,Family medicine ,medicine ,Humans ,Philadelphia Chromosome ,business - Abstract
A. M. Vannucchi1, T. Barbui2, F. Cervantes3, C. Harrison4, J.-J. Kiladjian5, N. Kroger6, J. Thiele7 & C. Buske8 on behalf of the ESMO Guidelines Committee* Department of Experimental and Clinical Medicine, University of Florence, Florence; Hematology and Foundation for Research, Ospedale Papa Giovanni XXIII, Bergamo, Italy; Department of Hematology, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain; Department of Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; Centre d’Investigations Cliniques (INSERM CIC1427), Hopital Saint-Louis and Paris Diderot University, Paris, France; Department of Stem Cell Transplantation, University Hospital Hamburg, Hamburg; University of Cologne, Cologne; Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research, University Hospital Ulm, Ulm, Germany
- Published
- 2015
32. Treatment of high risk ET – data from the EXELS study
- Author
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Carlos Besses, Gunnar Birgegård, Martin Griesshammer, Heinrich Achenbach, Mohamed Hamdani, Luigi Gugliotta, Claire N. Harrison, and J. J. Kiladjian
- Subjects
Cancer Research ,medicine.medical_specialty ,Acute leukemia ,Pregnancy ,Pediatrics ,Essential thrombocythemia ,business.industry ,Incidence (epidemiology) ,Hematology ,Anagrelide ,medicine.disease ,Gastroenterology ,Hydroxycarbamide ,medicine.anatomical_structure ,Oncology ,Internal medicine ,White blood cell ,Cohort ,medicine ,business ,medicine.drug - Abstract
Background The Evaluation of Xagrid Efficacy and Long-term Safety (EXELS) study (NCT00567502) is the largest prospective observational cohort of high-risk patients with essential thrombocythemia (ET) reported to date. Objectives The primary objective were safety and pregnancy outcomes of anagrelide (ANA) compared with other cytoreductive therapies (CRT). Secondary objectives included efficacy, measured by the incidence of thrombohemorrhagic events and platelet reduction. Methods High-risk patients (≥1 of age >60 years, previous thrombotic event, platelet count >1000 × 10 9 /L) with ET were enrolled across 13 countries in Europe between 2005 and 2009. Pts were required to be receiving CRT. Data, including events predefined in the protocol (PDEs), were collected every 6 months for 5 years for all patients. Event rates are presented as number of patients per 100 patient-years exposure and by treatment at time of event. Event rates are provided rather than p values due to the observational nature of the study. Preliminary final data are presented and final data, including platelet response and pregnancy results, will be available at ASH. Recently, results have remained stable and conclusions are not expected to change. Results 3649 patients were categorized according to treatment at registration as follows: ANA (n=804), ANA + other CRT (n=141), other CRT (n=2666) and no CRT (n=38). Over 80% of patients received either hydroxycarbamide (HC) or ANA, and 69.8% of patients received antiaggregatory therapy. At registration, median age was lower in the ANA (55.5 years, range 18–89) and ANA + other CRT (59.0 years, range 22–88) groups vs the other CRT group (70.0 years, range 17–95). The arterial thrombotic event rate was similar in ANA (1.63) and other CRT (1.62) groups, whereas venous thrombotic event rates differed (0.35 vs 0.57). The major hemorrhagic event rate was highest in the ANA group, especially in patients also treated with anti-aggregatory therapy (1.24). 105 patients transformed to myelofibrosis (MF) and 62 to acute leukemia (AL). Transformation to MF rates were similar in the ANA (1.31) and ANA + other CRT (1.27) groups, but lower in the other CRT (0.32) group. Rate of transformation to AL was 0.17, 0.46, and 0.33, respectively. In patients who had only ever received either ANA or HC, rate of transformation to MF was higher in the ANA vs HC group (0.78 vs 0.17) whereas transformation to AL was higher in the HC vs ANA group (0.22 vs 0). All patients who ever received ANA and transformed to AL had also received prior HC. PDEs of greatest interest are displayed in Table 1. Non-hematological malignancy was the most frequent PDE in the other CRT group. 57.4% of deaths were attributed to a PDE; transformation (event rate, 1.9), most frequently to AL (1.3), and non-hematological malignancies (1.6) were the most frequent causes of PDE-related death. No unexpected side effects were noted. There were 54 pregnancies, of which 41 were successful (76%). The proportion of patients with a white blood cell (WBC) count >15 × 10 9 /L at any time was higher in patients who died (12.5%) vs alive patients (6.1%) and in patients who had transformed (15.7%) vs those who did not transform (5.7%). Conclusion Patients receiving ANA were younger than those receiving other CRT. Thrombotic event rates were low; arterial events were similar between ANA and other CRT groups, and venous events were lower in the ANA vs other CRT group. Hemorrhage was most frequent in the ANA + anti-aggregatory therapy group, whereas non-hematological malignancy was most frequent in the other CRT group. Transformation to MF was more frequent in the ANA group, whereas transformation to AL was more frequent in the HC group. The incidence of death and transformation was higher in patients with a WBC count >15 × 10 9 /L.
- Published
- 2016
33. Erratum: Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis
- Author
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C N Harrison, A M Vannucchi, J-J Kiladjian, H K Al-Ali, H Gisslinger, L Knoops, F Cervantes, M M Jones, K Sun, M McQuitty, V Stalbovskaya, P Gopalakrishna, and T Barbui
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2017
34. Use of the 46/1 haplotype to model JAK2(V617F) clonal architecture in PV patients: clonal evolution and impact of IFNα treatment
- Author
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J J Kiladjian, Michaela Fontenay, Christine Chomienne, F. Favale, Jean-Luc Villeval, Salma Hasan, Eric Solary, J P Le Couedic, B Monte-Mor, Catherine Lacout, Bruno Cassinat, Christine Dosquet, Nicole Casadevall, Isabelle Plo, Nathalie Droin, and William Vainchenker
- Subjects
Genetics ,Cancer Research ,Clonal architecture ,Haplotype ,Interferon-alpha ,Hematology ,Biology ,Janus Kinase 2 ,Hematopoietic Stem Cells ,Somatic evolution in cancer ,Models, Biological ,Clonal Evolution ,Oncology ,Haplotypes ,hemic and lymphatic diseases ,Mutation ,Humans ,JAK2 V617F ,Polycythemia Vera ,Alleles - Abstract
Use of the 46/1 haplotype to model JAK2 V617F clonal architecture in PV patients: clonal evolution and impact of IFNα treatment
- Published
- 2013
35. Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study
- Author
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S. Reading, Heike L. Pahl, Joop H. Jansen, Adam Ivey, Susanna Akiki, B.A. van der Reijden, N Maroc, M.J. Percy, E. Oppliger Leibundgut, K Tobal, Mary Frances McMullin, J. Bryon, David Grimwade, Albert Gruender, Tamara Alpermann, Niels Pallisgaard, A Bench, J J Kiladjian, Claire N. Harrison, Jelena V. Jovanovic, Nicholas C.P. Cross, Sally Jeffries, Paola Guglielmelli, G Nickless, Alessandro M. Vannucchi, Bridget S. Wilkins, T Barbui, Donal P. McLornan, Bruno Cassinat, Alessandro Pancrazzi, K Cuthill, Todd W. Kelley, Amy V. Jones, Sylvie Hermouet, K. Yeoman, Susanne Schnittger, S. Schwemmers, J. T. Prchal, Christine Chomienne, and Eric Lippert
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Serial dilution ,Disease Response ,business.industry ,Essential thrombocythemia ,Hematology ,medicine.disease ,Minimal residual disease ,Donor lymphocyte infusion ,Clinical trial ,Transplantation ,Real-time polymerase chain reaction ,Internal medicine ,hemic and lymphatic diseases ,Immunology ,medicine ,business ,610 Medicine & health - Abstract
Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.
- Published
- 2013
36. Does increasing the JAK2V617F assay sensitivity allow to identify more patients with MPN?
- Author
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J J Kiladjian, Christine Dosquet, Nadine Bonnin, Bruno Cassinat, Lionel Adès, Christine Chomienne, M L Menot, Eirini Kouroupi, and William Vainchenker
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Chronic neutrophilic leukemia ,Hematology ,Hematocrit ,Trisomy 8 ,medicine.disease ,Gastroenterology ,Polycythemia vera ,medicine.anatomical_structure ,Oncology ,Internal medicine ,Immunology ,Medicine ,Bone marrow ,Allele ,business ,Myelofibrosis ,Letter to the Editor ,Whole blood - Abstract
The detection of the JAK2V617F mutation has become an essential tool in BCR-ABL1-negative myeloproliferative neoplasms (MPNs) diagnosis, as it is present in 95% of polycythemia vera (PV) patients and 60% of essential thrombocytemia (ET) or myelofibrosis patients.1 JAK2V617F-positive MPNs are different from other hematological malignant disease in that, although the JAK2V617F mutation is considered as the causative origin of the disease, the tumor burden at the time of diagnosis as assessed by the % of JAK2V617F alleles in peripheral blood or bone marrow can vary from 100% to very low levels with no correlation to blood cell counts. It is still undefined which lowest level might be detected to allow the diagnosis of every MPN patients. Using the Mustascreen kit (Ipsogen, Marseilles, France), the detection limit of which was close to 2%, most of the patients were easily classified as positive or negative. However, some rare patients were considered as doubtful because the level of fluorescence detected from the mutant probe was between the negative control and the 2% reference positive kit control. Recently, we decided to move toward a more sensitive method, the Mutaquant kit (Ipsogen), characterized by a detection limit close to 0.1%. DNA was extracted from whole blood using the QIA-AMP DNA blood mini kit (Qiagen, Hilden, Germany). In the few months after we adopted a more sensitive method, we identified positive patients among patients previously tested negative. These results raised two questions: who are the patients with very low levels of JAK2V617F mutation and consequently what level of sensitivity a method should have in a routine diagnosis setting. All patients included have given informed consent for this study, which has been approved by the local ethics committee. To assess the specificity of the Mutaquant method, 49 samples taken from blood donors were tested and no sample was detected as positive using a cut-off of 0.1%. Next, we diluted one 100% mutated patient DNA sample in a negative one. The 10−2 and 10−3 dilutions were measured at 1.2% and 0.1%, respectively, whereas the 10−4 dilution was found negative. These results confirmed the lower detection limit of this method to be 0.1% mutant allele burden. Within 6 months after introducing Mutaquant in a routine setting, we prospectively investigated 688 patients. Overall, 497 were tested for the first time, whereas 191 had already been analyzed previously using Mutascreen method. In 98 cases, the previous sample was positive and the Mutaquant result confirmed the positivity. In 93 cases, the previous result was negative, but in 7 of them the Mutaquant method detected a low level of JAK2V617F mutant allele (Table 1). When reanalyzed using the novel method, a low level of positivity was also detected on a frozen aliquot of the previous sample for these seven patients. In three cases several DNA samples were available, which were all found positive with Mutaquant, even samples taken as far as 5 years before, with a constant level of positivity throughout time. Of these seven patients, three were suspected of having ET, one presented with an isolated elevated hematocrit and one with a myelofibrosis. Patient 6 presented with a high WBC count, normal RBC and platelet counts, circulating immature myeloid cells and trisomy 8 in bone marrow cells. A chronic neutrophilic leukemia, a rare entity in which JAK2V617F has been reported,2 is unlikely in this case because of immature circulating myeloid cells and the absence of splenomegaly or segmented neutrophils. Patient 7 presented with unexplained repeated pulmonary embolisms without any hematological abnormality and a red cell mass in the normal range, excluding a polycythemia. The impact of the mutation in this patient is still questioning as JAK2V617F in thrombotic syndromes is frequent in splanchnic vein thrombosis3, but extremely rare in unprovoked thrombosis.4 We analyzed DNA from erythroid colonies from patient 3 and, in line with the DNA from total blood (1%), we found one JAK2V617F heterozygous colony among 48 tested, confirming the existence of a very low mutant allele burden. Table 1 Biological and clinical data of seven patients found positive, although repeatedly tested negative previously An unsolved question is whether a mutant allele burden of 1% or less really reflects the tumor burden and whether the patients found with less than 1% of JAK2V617F allele burden can be classified as MPN patients, as the WHO classification do not require quantitative analysis.5 In ET, a restriction of the mutation to the megakaryocytic lineage could lead to underestimation of the mutated cells percentage when analyzing blood DNA. Platelet RNA may be a better material to evaluate the tumor allele burden in some cases. We excluded the presence of an additional mutation in MPL (MPL Mutascreen kit) or the exon 12 of JAK2 (as previously described6) as driving the phenotype for every patient with less than 1% allele burden. Some studies reported the presence of extremely low levels (
- Published
- 2012
37. Traitement des syndromes myéloprolifératifs Philadelphie-négatifs
- Author
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J.-J. Kiladjian
- Abstract
Les prises en charge de la polyglobulie de Vaquez (PV) et de la thrombocytemie essentielle (TE) presentent de nombreux points communs du fait de grandes similitudes dans la physiopathologie, la presentation clinique et les complications de ces deux syndromes myeloproliferatifs (SMP) Philadelphie-negatifs. Par exemple, la mutation JAK2V617F est retrouvee dans plus de 90 % des PV et environ 60 % des TE, les deux pathologies peuvent se presenter avec une hyperleucocytose qui vient d’ etre recemment associee a un risque augmente de thrombose au cours du suivi, et le traitement de ces deux SMP est justifie du fait d’un risque vasculaire eleve a court et moyen terme. Au long cours, ces deux hemopathies partagent egalement un risque d’evolution vers la myelofibrose (MF), un syndrome myelodysplasique (SMD) ou une leucemie aigue (LA), ce risque pouvant etre influence par le traitement recu pendant la phase chronique de la maladie. La prise en charge de ces patients consiste donc d’une part a evaluer le risque vasculaire afin de traiter efficacement par un agent cytoreducteur les patients a haut risque, et d’autre part a adapter la strategie selon l’ âge des patients au diagnostic pour eviter une exposition prolongee a des agents potentiellement leucemogenes. Parmi ces SMP Philadelphie-negatifs, la myelofibrose primitive (MFP) a une place a part du fait d’une presentation tres heterogene (notamment en ce qui concerne la numeration formule sanguine — NFS) et d’un pronostic souvent bien plus pejoratif a court ou moyen terme, justifiant parfois le recours a une allogreffe de cellules souches hematopoietiques.
- Published
- 2011
38. Folliculite amicrobienne et photosensibilité liées à un nouvel inhibiteur de Jak : le ruxolitinib
- Author
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Martine Bagot, J.-J. Kiladjian, Marisa Battistella, M. Bezier, A. Andreoli, M. Jeanmougin, and C. Lebbé
- Subjects
Dermatology - Published
- 2013
39. [Extramedullary blastic transformation revealed by a prolonged fever during the course of a 5q- syndrome]
- Author
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C, Chehensse, T, Braun, A-S, Morin, J, Stirnemann, P, Agranat, L, Boukari, N, Aras, J-J, Kiladjian, M, Ziol, P, Fenaux, and O, Fain
- Subjects
Leukemia, Myeloid, Acute ,Fever ,Liver ,Leukemic Infiltration ,Myelodysplastic Syndromes ,Humans ,Female ,Middle Aged - Abstract
Fever during a myelodysplastic syndrome can be due to infectious complications, systemic disease or acute transformation with clonal evolution.A 51-year-old woman, with a 5q- syndrome and neutropenia, presented with a several week fever duration. Infectious work-up was negative and therapy with antibiotics had no influence on the clinical course. Neither bone marrow nor blood blasts were detected, but liver biopsy demonstrated significant blast infiltration compatible with the diagnosis of acute myeloid leukaemia (AML).The absence of blasts in blood or bone marrow does not exclude the malignant transformation of a myelodysplastic syndrome to AML. Tissue biopsy may be necessary to confirm the leukaemic progression.
- Published
- 2008
40. Essential thrombocythemias without V617F JAK2 mutation are clonal hematopoietic stem cell disorders
- Author
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J J Kiladjian, Jean Briere, Bernard Grandchamp, Stéphane Giraudier, Nicole Balitrand, Carole Conejero, N. Elkassar, Pierre Fenaux, Gilles Hetet, Bruno Cassinat, and Christine Chomienne
- Subjects
Adult ,Cancer Research ,Adolescent ,Alpha interferon ,hemic and lymphatic diseases ,Proto-Oncogene Proteins ,Protein-Tyrosine Kinases ,Humans ,Hydroxyurea ,Aged ,Janus kinase 2 ,biology ,Jak2 mutation ,Follow up studies ,Thrombocythemias ,food and beverages ,Interferon-alpha ,Hematology ,Janus Kinase 2 ,Middle Aged ,Hematopoietic Stem Cells ,Clone Cells ,Clonal Hematopoietic Stem Cell ,Treatment Outcome ,Oncology ,Immunology ,Mutation (genetic algorithm) ,Mutation ,Cancer research ,biology.protein ,Female ,hormones, hormone substitutes, and hormone antagonists ,Follow-Up Studies ,Thrombocythemia, Essential - Abstract
Essential thrombocythemias without V617F JAK2 mutation are clonal hematopoietic stem cell disorders
- Published
- 2006
41. The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow
- Author
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Esther Zipperer, Natalie A. Twine, Matthew Arno, Ghulam J. Mufti, Guillermo Sanz, Norbert Gattermann, Joop Gaken, Azim M Mohamedali, Nigel Westwood, Petar Antunovic, Ulrich Germing, Zaida García-Casado, A.A.N. Giagounidis, Szabolcs Benedek, José Cervera, Bruno Cassinat, J J Kiladjian, W Ingram, B. Czepulkowski, Júlia Tamáska, J Csomer, Judit Várkonyi, T. Kontou, Pierre Fenaux, and Nicholas Lea
- Subjects
Adult ,Genetic Markers ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.disease_cause ,Myeloproliferative Disorders ,Bone Marrow ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Point Mutation ,Aged ,Aged, 80 and over ,Mutation ,Janus kinase 2 ,Hematology ,biology ,Point mutation ,Janus Kinase 2 ,Middle Aged ,medicine.anatomical_structure ,Oncology ,Genetic marker ,Cancer research ,biology.protein ,Chromosomes, Human, Pair 5 ,Female ,Bone marrow ,Chromosome Deletion ,JAK2 V617F ,Cell Division - Abstract
The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow
- Published
- 2006
42. P126 Treatment of progression of myeloproliferative neoplasm (MPN) to MDS/AML by azacytidine (AZA): a report on 44 patients (pts)
- Author
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C. Gardin, Y. Chait, J J Kiladjian, Bruno Cassinat, Raphael Itzykson, Murielle Roussel, Christian Recher, C. Zerhouni, Francois Dreyfus, Pierre Fenaux, Lionel Adès, Thomas Cluzeau, Emmanuel Raffoux, Sylvain Thepot, and B. Quesnel
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Univariate analysis ,Multivariate analysis ,biology ,business.industry ,Myelodysplastic syndromes ,CD44 ,Myeloid leukemia ,Hematology ,urologic and male genital diseases ,medicine.disease ,Risk groups ,hemic and lymphatic diseases ,Internal medicine ,Cohort ,medicine ,biology.protein ,business ,Myeloproliferative neoplasm - Abstract
Aberrant expression of the adhesion molecule CD44 correlates with poor prognosis in various neoplasms. To evaluate the prognostic impact of CD44 in myelodysplastic syndromes (MDS) serum levels of soluble CD44 (sCD44) were measured in 130 MDS patients using an enzymelinked immunosorbent assay (ELISA). sCD44 levels were significantly elevated in MDS patients compared to healthy donors (p< 0.05), and were found to correlate with distinct FAB subtypes. The highest levels of sCD44 were found in patients with CMML and in patients with MDS transformed into acute myeloid leukemia (AML). In univariate analysis elevated levels of sCD44 s were significantly correlated with shorter overall survival in MDS-patients (9 versus 37 months; p< 000). In multivariate analysis sCD44 s displayed prognostic significance for survival independent from the International Prognosis Scoring System (IPSS). To test for refined prognostication, each IPSS risk group was split into two separate categories based on sCD44 s levels. Using this approach, MDS patients with a shorter survival were identified both in the IPSS low-risk (p = 0.014) and in the IPSS Int-1 group (p = 0.031). The CD44 s-adjusted IPSS defines a cohort of MDS patients with unfavorable prognosis within the low and intermediate-1 IPSS groups, which might be helpful in risk stratification and in therapeutic algorithms.
- Published
- 2009
43. Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis
- Author
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Hans Michael Kvasnicka, R. Landolfi, Marie-Claire Martyré, Heinz Gisslinger, Eva Lengfelder, P. Stark, Jean Briere, M.C. Le Bousse-Kerdilès, Martin Griesshammer, A. Wehmeier, A.C. Green, Roberto Marchioli, Hans Carl Hasselbalch, N.I. Berlin, Francisco Cervantes, T.C. Pearson, Tiziano Barbui, Luigi Gugliotta, E. Hansmann, Guido Finazzi, Jack Kutti, Richard T. Silver, John T. Reilly, Juergen Thiele, S.M. Fruchtmann, P. J. J. van Genderen, J J Kiladjian, Jan Jacques Michiels, M. Bazzan, Jean-Loup Demory, and Ph. Guardiola
- Subjects
Pathology ,medicine.medical_specialty ,Myeloid ,Hydroxycarbamide ,Diagnosis, Differential ,Polycythemia vera ,Bone Marrow ,Metaplasia ,Internal Medicine ,medicine ,Humans ,Myelofibrosis ,Polycythemia Vera ,Megakaryocytopoiesis ,Bone Marrow Transplantation ,Myeloproliferative Disorders ,Aspirin ,Essential thrombocythemia ,business.industry ,Anagrelide ,medicine.disease ,Prognosis ,Thrombocytopenia ,medicine.anatomical_structure ,Primary Myelofibrosis ,Interferons ,medicine.symptom ,business ,Megakaryocytes ,Platelet Aggregation Inhibitors ,medicine.drug ,Follow-Up Studies ,Granulocytes - Abstract
According to strict clinical, hematological and morphological criteria, the Philadelphia (Ph) chromosome negative chronic myeloproliferative disorders essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid (megakaryocytic/granulocytic) metaplasia (AMM) or idiopathic myelofibrosis (IMF) are three distinct disease entities with regard to clinical manifestations, natural history and outcome in terms of life expectancy. As clonality studies have clearly demonstrated that fibroblast proliferation in AMM, as well as in many other conditions such as advanced stages of Ph(+)-essential thrombocythemia, Ph(+)-granulocytic leukemia, and Ph(-)-polycythemia vera, is polyclonal indicating that myelofibrosis is secondary to the megakaryocytic granulocytic metaplasia in these various conditions, AMM is illogically labeled as IMF. As abnormal megakaryocytic granulocytic metaplasia is the essential feature preceding the early prefibrotic stage of AMM, the term essential megakaryocytic granulocytic metaplasia (EMGM) can readily be used to characterize this condition more appropriately at the biological level. Clinical, hematological and morphological characteristics, in particular megakaryocytopoiesis and bone marrow cellularity, reveal diagnostic features, which enable a clear-cut distinction between ET, PV and EMGM or classical IMF. The characteristic increase and clustering of enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or only slightly increased cellular bone marrow represent the hallmark of ET. The characteristic increase and clustering of enlarged mature and pleiomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses are the specific diagnostic features of untreated PV. EMGM, including the early prefibrotic stages as well as the various myelofibrotic stages of classical IMF appear to be a distinct neoplastic dual proliferation of abnormal megakaryopoiesis and granulopoiesis. The histopathology of the bone marrow in prefibrotic EMGM and in classical IMF is dominated by atypical, enlarged and immature megakaryocytes with cloud-like immature nuclei, which are not seen in ET and PV at diagnosis and during follow-up. Myelofibrosis in ET, PV and EMGM is graded into: no reticulin fibrosis (MF0), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor or moderate collagen fibrosis (MF2) and advanced collagen fibrosis with osteosclerosis (MF3). Myelofibrosis is not a feature of ET at diagnosis and during long-term follow-up. Myelofibrosis may be present in a minority of PV-patients at diagnosis and usually becomes apparent during long-term follow-up in the majority of PV-patients. Myelofibrosis secondary to the abnormal megakaryocytic and granulocytic myeloproliferation constitutes a prominent feature in the majority of EMGM/IMF at time of diagnosis and usually progresses more or less rapidly during the natural history of the disease. Life expectancy is normal in ET, normal during the 1st ten years and compromised during the 2nd ten years follow-up in PV, but significantly shortened in the prefibrotic stage of EMGM as well as in the various myelosclerotic stages of classical IMF. First line treatment options in prospective randomized clinical trials of newly diagnosed MPD-patients are control of platelet function with low-dose aspirin versus reduction of platelet count with anagrelide, interferon or hydroxyurea in ET; control of platelet and erythrocyte counts by interferon alone versus bloodletting plus hydroxyurea on indication in PV; interferon versus no treatment in the early stages of EMGM; a wait and see strategy in the fibrotic stages of EMGM or classical IMF with favorable prognostic factors, and bone marrow transplantation in classical IMF with poor prognostic factors at presentation or during short-term follow-up.
- Published
- 1999
44. Classification of myeloproliferative disorders in the JAK2 era: is there a role for red cell mass?
- Author
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Bruno Cassinat, C Laguillier, S Burcheri, J J Kiladjian, Claude Gardin, V de Beco, Pierre Fenaux, and Christine Chomienne
- Subjects
Cancer Research ,medicine.medical_specialty ,Myeloproliferative Disorders ,Janus kinase 2 ,biology ,Red Cell ,business.industry ,food and beverages ,Polycythemia ,Hematology ,Janus Kinase 2 ,Surgery ,Diagnosis, Differential ,Erythrocyte volume ,Oncology ,hemic and lymphatic diseases ,biology.protein ,Cancer research ,Humans ,Medicine ,business ,hormones, hormone substitutes, and hormone antagonists ,Erythrocyte Volume - Abstract
Classification of myeloproliferative disorders in the JAK2 era: is there a role for red cell mass?
- Published
- 2007
45. Megakaryocytes and platelets in myeloproliferative disorders
- Author
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J, Briere, J J, Kiladjian, and E, Peynaud-Debayle
- Subjects
Blood Platelets ,Myeloproliferative Disorders ,Bone Marrow ,Primary Myelofibrosis ,Chronic Disease ,Humans ,Megakaryocytes ,Clone Cells ,Hematopoiesis - Abstract
Increased megakaryocyte (MK) proliferation in bone marrow is a feature common to the three Ph-negative myeloproliferative disorders (MPDs), i.e. essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis with splenic myeloid metaplasia (MMM), and to chronic myelocytic leukaemia (CML). Enlarged MKs with multilobulated nuclei and cell clustering in close proximity are the hallmark of all the Ph negative MPDs. Clonality of haematopoietic cells, based on X chromosome inactivation, can now be studied in a majority of female patients in all nucleated cell fractions as well as in platelets. Cytofluorometric studies have demonstrated a shift towards higher ploidy classes in PV and ET MKs which may be useful in discriminating between both primary and reactive thrombocytosis and CML patients which show a significant shift to lower MK ploidy values. The role of MK proliferation on the evolution of myelofibrosis common to MPDs has been firmly established. Implication of platelet-derived growth factor (PDGF) in myelofibrosis has already been demonstrated. More recently transforming growth factor beta (TGF beta) synthesized and secreted by MK has been implicated in fibroblasts stimulation. A significant increase in circulating colony-forming units of MKs (CFU-MK) has been repeatedly observed in MPDs as well as a spontaneous MK colony formation in a majority of ET patients. Hypersensitivity to thrombopoietin (TPO) in relation to a functional defect of the TPO-MPL pathway may play a major role in spontaneous MK growth. There is no currently available test of platelet functions able to predict the risk of occurrence of thrombotic or haemorrhagic complications in MPD patients. However, the role of platelet activation in the pathogenesis of ischaemic erythromelalgia has been established and a correlation between presenting haemorrhagic manifestations and platelet counts in excess of 1000 x 10(9)/l has been found.
- Published
- 1997
46. Systematic Evaluation of DNA-Based Quantitative-Polymerase Chain Reaction (Q-PCR) Assays to Track Treatment Response in Patients with JAK2-V617F Associated Myeloproliferative Neoplasms: A Joint European LeukemiaNet/ MPN&MPNr-EuroNet Study
- Author
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Todd W. Kelley, S. Schwemmers, Eric Lippert, B.A. van der Reijden, K. Yeoman, A Bench, N Maroc, David Grimwade, Adam Ivey, K Tobal, J. T. Prchal, Christine Chomienne, S. Reading, Sylvie Hermouet, Bridget S. Wilkins, Tiziano Barbui, M.J. Percy, G. Nickless, Bruno Cassinat, Paola Guglielmelli, Mary Frances McMullin, Claire N. Harrison, Alessandro Pancrazzi, Albert Gruender, Alessandro M. Vannucchi, J J Kiladjian, E. Oppliger Leibundgut, Jelena V. Jovanovic, Kirsty Cuthill, and Heike L. Pahl
- Subjects
Peptidylprolyl isomerase ,Genetics ,Oncology ,medicine.medical_specialty ,business.industry ,Essential thrombocythemia ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Minimal residual disease ,law.invention ,Transplantation ,European LeukemiaNet ,Real-time polymerase chain reaction ,law ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Allele ,business ,Polymerase chain reaction - Abstract
Abstract 2812 Since the discovery of the JAK2-V617F mutation, the relative level of the mutant allele has been widely studied to gain further insights into the biology of myeloproliferative neoplasms and to establish utility in predicting clinical outcome. Mutant allele burden has been correlated with risk of thrombotic events in essential thrombocythemia, severity of the disease phenotype in polycythemia vera (PV) and survival in primary myelofibrosis (PMF). JAK2-V617F has also been quantified to assess disease response, with significant reductions in allele burden reported in PV patients following interferon (IFN) α-2b and pegylated IFN α-2a treatment. Moreover, serial DNA-based quantitative polymerase chain reaction (Q-PCR) assays have been used after allogeneic transplantation for myelofibrosis to predict outcome and guide donor lymphocyte infusion. With quantification of JAK2-V617F being considered an endpoint in a number of trials with novel agents including JAK2 inhibitors, it is important that assays are robust, mutant-specific and afford a suitable level of sensitivity. However, numerous JAK2-V617F Q-PCR assays have now been published, which based on experience of molecular monitoring in other hematological malignancies, are likely to vary markedly in their performance. Indeed, this concern was confirmed by the results of a quality control (QC) exercise involving 5 European LeukemiaNet (ELN) laboratories, each with their own established JAK2-V617F Q-PCR assay, who reported markedly differing levels of mutant allele percentage (ranging from 23–80%) in a QC sample distributed by UK NEQAS that comprised a 1 in 30 dilution of HEL cells (which harbor multiple copies of JAK2-V617F and lack the wild type [WT] JAK2 allele) in K562 cells (WT JAK2). To address this issue, a joint initiative was established within European LeukemiaNet between the Chronic Myeloproliferative Diseases and Minimal Residual Disease working groups (WP9 & WP12) to systematically evaluate a range of published and “in-house” JAK2-V617F assays, with the aim of identifying sensitive mutant-specific assays that perform similarly on different Q-PCR platforms – factors of fundamental importance for reliable tracking of disease response. The study involved 12 expert centers - in 6 European countries and included 1 US laboratory, which between them used Q-PCR platforms from 3 different manufacturers. The study involved central distribution of DNA from serial dilutions of JAK2-V617F mutant cell lines (HEL &/or UKE-1) in K562 and plasmid standards for JAK2 WT, JAK2-V617F and independent control genes (albumin, cyclophilin). Reagents for each assay were coded and also centrally distributed; reaction conditions for each coded assay were provided. Laboratories with established published or in-house Q-PCR assays were encouraged to perform these in parallel with the coded test assays on the distributed QC materials, to control for local variations in test conditions. Data from each QC round were submitted by participating laboratories for independent central analysis (Dept. of Genetics, King's College London); conclusions were drawn concerning the performance of the various assays before breaking the code to reveal their identities. Overall, 7 successive QC rounds were conducted, evaluating 9 assays (6 published, 3 unpublished “in-house”). Six assays were eliminated, due to insufficient/inferior sensitivity (n=5) or inconsistent performance (n=1). Of the 3 assays with better performance profile, the assay published by Lippert et al (Blood 2006;108 :1865) reliably quantified JAK2-V617F across the diagnostic range, with consistent results obtained between laboratories irrespective of Q-PCR platform. The 2 remaining assays (Larsen et al, Br J Haematol. 2007;136 :745 & in-house assay from the Oppliger Leibundgut lab [Bern]), afforded better sensitivity, capable of detecting a 0.08–0.008 % level of JAK2-V617F in DNA preparations from HEL and K562 cells. The latter assays were tested on serial post-transplant samples from 2 patients allografted for JAK2-V617F mutant PMF, successfully identifying the presence of residual disease, complementing chimerism analysis to predict clinical outcome. In conclusion, this ELN study has identified robust assays suitable for quantifying JAK2-V617F in clinical trials and which merit further investigation as a tool to guide management of patients undergoing allogeneic transplant. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2011
47. 291 Prognostic impact of JAK2V617F mutation in MDS: a matched case control study
- Author
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Christian Rose, G. Tertian, Lionel Adès, Jean-Loup Demory, B. de Renzis, Sophie Raynaud, Odile Beyne-Rauzy, Eric Wattel, Pierre Fenaux, Aurélie Cabrespine, Florence Nguyen-Khac, Françoise Boyer, Jean-Yves Cahn, Laurent Knoops, J. J. Kiladjian, V. de Mas, Dominique Bordessoule, Jean-Christophe Ianotto, and Michaela Fontenay
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Case-control study ,Hematology ,Jak2v617f mutation ,business - Published
- 2011
48. High Response Rate to Darbopoetin Alfa in 'Low Risk' MDS : Results of a Phase II Study
- Author
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Stéphane Cheze, J J Kiladjian, L. Voilliat, D. Vassilief, P. Agape, E. Rosenthal, Lionel Mannone, M.C. Quarre, Francois Dreyfus, Mo Beyne-Rouzy, Jean-François Bernard, Sophie Park, S. Vaultier, F. Hamza, Pierre Fenaux, Stéphane Giraudier, and C. Gardin
- Subjects
Response rate (survey) ,medicine.medical_specialty ,Anemia ,business.industry ,Immunology ,Phases of clinical research ,Alpha (ethology) ,Half-life ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Surgery ,Lenograstim ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Platelet ,Adverse effect ,business - Abstract
Background : Recombinant Erythopoietin (EPO) alfa or beta, when used alone at 10 to 20 000 units, three times weekly, improves anemia in 25 to 30 % of low risk MDS. By combining G-CSF to EPO, the response rate increases to 40 to 45 %. Darbopoietin alfa is a highly glycosylated form of EPO with prolonged half life, allowing weekly (or even once every second week) administration. We report results of a phase II study of Darbopoietin alpha in low risk MDS. Patients and Treatment : Inclusion criteria were (i) MDS with < 10 % marrow blasts (ii) anemia requiring transfusion or Hb < 10g/dl (iii) serum epo level < 500 mU/ml (iiii) exclusion of other causes of anemia. Patients were treated with Darbopoietin 300 μg/week during at least 12 weeks. In the absence of response, G-CSF (lenograstim 150 μg, 3 times weekly) was added to Darbopoietin and a new evalution made after 12 weeks. Response was evaluated based on IWG criteria. In patients responding to Darbopoietin, intervals between 300 μg injections were adjusted to maintain Hb levels between 11 and 13g/dl. 55 patients were included. 2 were inevaluable due to severe sepsis (unrelated to darbopoietin) after 4 weeks of treatment and 13 were too early for evaluation. The 40 patients who received at least 12 weeks of darbopoietin included 20M/20F, median age was 77, morphology : 15 RA, 12 RARS, 12 RAEB1, 1 CMML ; Karyotype was favorable (21 %), intermediate (76 %), unfavorable (3%). IPSS was low (38 %), int 1 (52 %), int 2 (10 %), serum epo levels ranged from 10 to 490 mU/ml (median 68). Median interval from diagnosis of MDS was 12 months (range 3–136), 6 patients had previously received EPO alfa or beta without success. Results: 24 of the evaluable patients (60 %) responded at 12 weeks with Darbopoietin alone including HI - E major (n=19) and HI - E minor (n=5). No response was seen on granulocytes and platelets. 6 patients reached Hb > 15g/dl and 2 Hb > 16g/dl. Of the non responders at 12 weeks , 8 received further Darbopoietin + G-CSF and 2 of them responded after 12 weeks of combined treatment. 16 of the responders were evaluable for maintenance treatment (during 8 to 24 weeks) and intervals between injections required to maintain response could be prolonged to 2 or 3 weeks in 9 of them. 2 relapses were seen during maintenance, in 2 patients with HI-E minor. No side effects were observed. Pretreatment serum epo level, Karyotype and IPSS had no prognostic value on response. Response rates were 67 %, 42 % 67 % for RA, RARS and RAEB1, respectively (p=NS). 2/3 patients with 5 q- syndrome responded. Finally, 3 of the 6 patients previously unresponsive to EPO responded to darbopoietin. Conclusion : Results obtained with Darbopoietin alfa alone on the anemia of low risk MDS may be superior to those obtained with conventional EPO alone, and the drug is well tolerated. Randomized studies are obviously required to compare the effect of the different types of EPO on the correction of anemia of MDS patients.
- Published
- 2004
49. Screening for JAK2V617F and MPL515 Mutations in Idiopathic Pulmonary Fibrosis
- Author
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Dominique Valeyre, Bruno Cassinat, J J Kiladjian, Stéphane Giraudier, Hilario Nunes, Jean-Marc Naccache, Yurdagul Uzunhan, and Marianne Kambouchner
- Subjects
medicine.medical_specialty ,Idiopathic pulmonary fibrosis ,business.industry ,Internal medicine ,medicine ,medicine.disease ,business ,Gastroenterology
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