Author: "Cervantes F." / Topic: antineoplastic agents - Searchworks@Jio Institute Digital Library Search Results

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1. Genomic characterization of patients with polycythemia vera developing resistance to hydroxyurea.

Author: Alvarez-Larrán A, Díaz-González A, Such E, Mora E, Andrade-Campos M, García-Hernández C, Gómez-Casares MT, García-Gutiérrez V, Carreño-Tarragona G, Garrote M, Fernández-Ibarrondo L, Cervera J, Bellosillo B, Cervantes F, and Hernández-Boluda JC
Subjects: Humans, Polycythemia Vera drug therapy, Polycythemia Vera pathology, Prognosis, Survival Rate, Antineoplastic Agents pharmacology, Biomarkers, Tumor genetics, Drug Resistance, Neoplasm genetics, Gene Expression Regulation, Neoplastic drug effects, Genomics methods, Hydroxyurea pharmacology, Polycythemia Vera genetics
Published: 2021
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2. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia.

Author: Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, Clark RE, Cortes JE, Deininger MW, Guilhot F, Hjorth-Hansen H, Hughes TP, Janssen JJWM, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Mayer J, Nicolini F, Niederwieser D, Pane F, Radich JP, Rea D, Richter J, Rosti G, Rousselot P, Saglio G, Saußele S, Soverini S, Steegmann JL, Turkina A, Zaritskey A, and Hehlmann R
Subjects: Aniline Compounds therapeutic use, Clinical Decision-Making, Consensus Development Conferences as Topic, Dasatinib therapeutic use, Disease Management, Fusion Proteins, bcr-abl genetics, Fusion Proteins, bcr-abl metabolism, Gene Expression, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Life Expectancy trends, Monitoring, Physiologic, Nitriles therapeutic use, Pyrimidines therapeutic use, Quality of Life, Quinolines therapeutic use, Survival Analysis, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl antagonists & inhibitors, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors therapeutic use
Abstract: The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
Published: 2020
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3. Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms.

Author: De Stefano V, Carobbio A, Di Lazzaro V, Guglielmelli P, Iurlo A, Finazzi MC, Rumi E, Cervantes F, Elli EM, Randi ML, Griesshammer M, Palandri F, Bonifacio M, Hernandez-Boluda JC, Cacciola R, Miroslava P, Carli G, Beggiato E, Ellis MH, Musolino C, Gaidano G, Rapezzi D, Tieghi A, Lunghi F, Loscocco GG, Cattaneo D, Cortelezzi A, Betti S, Rossi E, Finazzi G, Censori B, Cazzola M, Bellini M, Arellano-Rodrigo E, Bertozzi I, Sadjadian P, Vianelli N, Scaffidi L, Gomez M, Cacciola E, Vannucchi AM, and Barbui T
Subjects: Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Disease-Free Survival, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Antineoplastic Agents administration & dosage, Brain Ischemia drug therapy, Brain Ischemia mortality, Fibrinolytic Agents administration & dosage, Hematologic Neoplasms drug therapy, Hematologic Neoplasms mortality, Myeloproliferative Disorders drug therapy, Myeloproliferative Disorders mortality, Platelet Aggregation Inhibitors administration & dosage, Stroke drug therapy, Stroke mortality
Abstract: We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment.
Published: 2018
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4. Sustained deep molecular responses in patients switched to nilotinib due to persistent BCR-ABL1 on imatinib: final ENESTcmr randomized trial results.

Author: Hughes TP, Leber B, Cervantes F, Spector N, Pasquini R, Clementino NCD, Schwarer AP, Dorlhiac-Llacer PE, Mahon FX, Rea D, Guerci-Bresler A, Kamel-Reid S, Bendit I, Acharya S, Glynos T, Dalal D, Branford S, and Lipton JH
Subjects: Cross-Over Studies, Humans, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl metabolism, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use
Published: 2017
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5. No influence of BCR-ABL1 transcript types e13a2 and e14a2 on long-term survival: results in 1494 patients with chronic myeloid leukemia treated with imatinib.

Author: Pfirrmann M, Evtimova D, Saussele S, Castagnetti F, Cervantes F, Janssen J, Hoffmann VS, Gugliotta G, Hehlmann R, Hochhaus A, Hasford J, and Baccarani M
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Young Adult, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl genetics, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Abstract: Purpose: The genomic break on the major breakpoint cluster region of chromosome 22 results in two BCR-ABL1 transcripts of different sizes, e14a2 and e13a2. Favorable survival probabilities of patients with chronic myeloid leukemia (CML) in combination with too small patient samples may yet have obstructed the observation of differences in overall survival of patients according to transcript type. To overcome potential power problems, overall survival (OS) probabilities and probabilities of CML-related death were analyzed in 1494 patients randomized to first-line imatinib treatment., Methods: OS probabilities and probabilities of dying of CML were compared using the log-rank or Gray test whichever was appropriate. Both tests were stratified for the EUTOS long-term survival score., Results: Between the groups with a single transcript, neither OS probabilities (stratified log-rank test: p = 0.106) nor probabilities of CML-related death were significantly different (stratified Gray test: p = 0.256). Regarding OS, the Cox hazard ratio (HR) of transcript type e13a2 (n = 565) to type e14a2 (n = 738) was 1.332 (95% CI 0.940-1.887). Considering probabilities of leukemia-related death, the corresponding subdistribution HR resulted in 1.284 (95% CI 0.758-2.176). Outcome did not change if patients with both transcripts (n = 191) were added to the 738 with type e14a2 only., Conclusions: The prognostic association of transcript type and long-term survival outcome was weak and without clinical relevance. However, earlier reported differences in the rate and the depth of molecular response could be relevant for the chance of successfully discontinuing TKI treatment. The effect of transcript type on molecular relapse after discontinuation is unknown, yet.
Published: 2017
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6. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia.

Author: Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, Baccarani M, Deininger MW, Cervantes F, Fujihara S, Ortmann CE, Menssen HD, Kantarjian H, O'Brien SG, and Druker BJ
Subjects: Adolescent, Adult, Aged, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cross-Over Studies, Cytarabine therapeutic use, Cytogenetic Analysis, Female, Follow-Up Studies, Humans, Imatinib Mesylate adverse effects, Intention to Treat Analysis, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Protein Kinase Inhibitors therapeutic use, Survival Analysis, Young Adult, Antineoplastic Agents therapeutic use, Imatinib Mesylate therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Abstract: Background: Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy., Methods: In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events., Results: The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment., Conclusions: Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).
Published: 2017
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7. Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response.

Author: Cervantes F, Correa JG, Pérez I, García-Gutiérrez V, Redondo S, Colomer D, Jiménez-Velasco A, Steegmann JL, Sánchez-Guijo F, Ferrer-Marín F, Pereira A, and Osorio S
Subjects: Adult, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Time Factors, Treatment Outcome, Antineoplastic Agents administration & dosage, Imatinib Mesylate administration & dosage, Leukemia, Myeloid, Chronic-Phase diagnosis, Leukemia, Myeloid, Chronic-Phase drug therapy
Abstract: To determine whether a lower imatinib dose could minimize toxicity while maintaining the molecular response (MR), imatinib dose was reduced to 300 mg daily in 43 patients with chronic myeloid leukemia (CML) in sustained deep molecular response to first-line imatinib 400 mg daily. At the time of dose reduction, median duration of the deep response was 4.1 (interquartile range (IQR) 2.2-5.9) years; molecular response was MR 4 , MR 4.5 , and MR 5 of the international scale in 6, 28, and 9 patients, respectively. Toxicity grade was 1, 2, and 3 in 28, 8, and 1 patients, respectively; 6 patients underwent dose reduction without having side effects. With a median of 1.6 (IQR 0.7-3.2) years on imatinib 300 mg daily, only one patient lost the deep molecular response to MR 3 . At the last follow-up, response was MR 3 , MR 4 , MR 4.5 , and MR 5 in 1, 3, 9, and 30 patients, respectively. Toxicity improvement was observed in 23 (62.2 %) of the 37 patients with side effects, decreasing to grade 0 in 20 of them. All but one anemic patients improved (p = 0.01), the median Hb increase in this subgroup of patients being 1 g/dL. In CML patients with sustained deep response to the standard imatinib dose, reducing to 300 mg daily significantly improves tolerability and preserves efficacy.
Published: 2017
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8. Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease.

Author: Geyer H, Scherber R, Kosiorek H, Dueck AC, Kiladjian JJ, Xiao Z, Slot S, Zweegman S, Sackmann F, Fuentes AK, Hernández-Maraver D, Döhner K, Harrison CN, Radia D, Muxi P, Besses C, Cervantes F, Johansson PL, Andreasson B, Rambaldi A, Barbui T, Bonatz K, Reiter A, Boyer F, Etienne G, Ianotto JC, Ranta D, Roy L, Cahn JY, Maldonado N, Barosi G, Ferrari ML, Gale RP, Birgegard G, Xu Z, Zhang Y, Sun X, Xu J, Zhang P, te Boekhorst PA, Commandeur S, Schouten H, Pahl HL, Griesshammer M, Stegelmann F, Lehmann T, Senyak Z, Vannucchi AM, Passamonti F, Samuelsson J, and Mesa RA
Subjects: Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Fatigue etiology, Female, Fever etiology, Humans, Hydroxyurea administration & dosage, Janus Kinases antagonists & inhibitors, Janus Kinases genetics, Male, Middle Aged, Pain etiology, Palpation, Prognosis, Prospective Studies, Pruritus etiology, Severity of Illness Index, Sweating, Weight Loss, Antineoplastic Agents adverse effects, Hydroxyurea adverse effects, Phlebotomy, Polycythemia Vera complications, Polycythemia Vera drug therapy, Splenomegaly etiology
Abstract: Purpose: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden., Patients and Methods: Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly)., Results: The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S)., Conclusion: The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present., (© 2015 by American Society of Clinical Oncology.)
Published: 2016
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9. Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial.

Author: Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, Masszi T, Mishchenko E, Jourdan E, Vannucchi AM, Drummond MW, Jurgutis M, Kuliczkowski K, Gheorghita E, Passamonti F, Neumann F, Patki A, Gao G, and Tefferi A
Subjects: Administration, Oral, Antineoplastic Agents adverse effects, Double-Blind Method, Drug Administration Schedule, Humans, Janus Kinase 2 antagonists & inhibitors, Janus Kinase 2 genetics, Janus Kinase 2 metabolism, Magnetic Resonance Imaging, Mutation, Organ Size, Primary Myelofibrosis diagnosis, Primary Myelofibrosis enzymology, Primary Myelofibrosis genetics, Protein Kinase Inhibitors adverse effects, Pyrrolidines adverse effects, Spleen diagnostic imaging, Spleen drug effects, Spleen pathology, Splenomegaly diagnosis, Splenomegaly enzymology, Sulfonamides adverse effects, Time Factors, Tomography, X-Ray Computed, Treatment Outcome, Antineoplastic Agents administration & dosage, Primary Myelofibrosis drug therapy, Protein Kinase Inhibitors administration & dosage, Pyrrolidines administration & dosage, Splenomegaly drug therapy, Sulfonamides administration & dosage
Abstract: Importance: Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating constitutional symptoms, and shortened survival. Fedratinib, a JAK2-selective inhibitor, previously demonstrated clinically beneficial activity in patients with MF in early-phase trials., Objective: To evaluate the efficacy and safety of fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF., Design, Setting, and Participants: Double-blind, randomized, placebo-controlled phase 3 study in 94 sites in 24 countries in which 289 adult patients (≥18 years of age) with intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF were randomly assigned between December 2011 and September 2012 to once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles., Main Outcomes and Measures: The primary end point was spleen response (≥35% reduction in spleen volume from baseline as determined by magnetic resonance imaging or computed tomography) at week 24 and confirmed 4 weeks later. The main secondary end point was symptom response (≥50% reduction in total symptom score, assessed using the modified Myelofibrosis Symptom Assessment Form)., Results: The primary end point was achieved by 35 of 96 (36% [95% CI, 27%-46%]) and 39 of 97 (40% [95% CI, 30%-50%]) patients in the fedratinib 400-mg and 500-mg groups, vs 1 of 96 (1% [95% CI, 0%-3%]) in the placebo group (P < .001). Symptom response rates at week 24 were 33 of 91 (36% [95% CI, 26%-46%]), 31 of 91 (34% [95% CI, 24%-44%]), and 6 of 85 (7% [95% CI, 2%-13%]) in the fedratinib 400-mg, 500-mg, and placebo groups, respectively (P < .001). Common adverse events with fedratinib treatment were anemia, gastrointestinal symptoms, and increased levels of liver transaminases, serum creatinine, and pancreatic enzymes. Encephalopathy was reported in 4 women who received fedratinib 500 mg/d. A diagnosis of Wernicke encephalopathy was supported by magnetic resonance imaging in 3 cases and suspected clinically in 1 case., Conclusions and Relevance: Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued., Trial Registration: clinicaltrials.gov identifier: NCT01437787.
Published: 2015
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10. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily.

Author: Hughes TP, Hochhaus A, Kantarjian HM, Cervantes F, Guilhot F, Niederwieser D, le Coutre PD, Rosti G, Ossenkoppele G, Lobo C, Shibayama H, Fan X, Menssen HD, Kemp C, Larson RA, and Saglio G
Subjects: Antineoplastic Agents adverse effects, Benzamides adverse effects, Drug Substitution, Follow-Up Studies, Humans, Imatinib Mesylate, Piperazines adverse effects, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Treatment Failure, Treatment Outcome, Antineoplastic Agents administration & dosage, Benzamides administration & dosage, Leukemia, Myeloid, Chronic-Phase drug therapy, Piperazines administration & dosage, Protein Kinase Inhibitors administration & dosage, Pyrimidines administration & dosage
Abstract: In a randomized, phase III trial of nilotinib versus imatinib in patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase, more patients had suboptimal response or treatment failure on front-line imatinib than on nilotinib. Patients with suboptimal response/treatment failure on imatinib 400 mg once or twice daily or nilotinib 300 mg twice daily could enter an extension study to receive nilotinib 400 mg twice daily. After a 19-month median follow up, the safety profile of nilotinib 400 mg twice daily in patients switching from imatinib (n=35) was consistent with previous reports, and few new adverse events occurred in patients escalating from nilotinib 300 mg twice daily (n=19). Of patients previously treated with imatinib or nilotinib 300 mg twice daily, respectively, 15 of 26 (58%) and 2 of 6 (33%) without complete cytogenetic response at extension study entry, and 11 of 34 (32%) and 7 of 18 (39%) without major molecular response at extension study entry, achieved these responses at any time on nilotinib 400 mg twice daily. Estimated 18-month rates of freedom from progression and overall survival after entering the extension study were lower for patients switched from imatinib (85% and 87%, respectively) versus nilotinib 300 mg twice daily (95% and 94%, respectively). Nilotinib dose escalation was generally well tolerated and improved responses in about one-third of patients with suboptimal response/treatment failure. Switch to nilotinib improved responses in some patients with suboptimal response/treatment failure on imatinib, but many did not achieve complete cytogenetic response (clinicaltrials.gov identifiers: 00718263, 00471497 - extension)., (Copyright© Ferrata Storti Foundation.)
Published: 2014
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11. Cytoreduction plus low-dose aspirin versus cytoreduction alone as primary prophylaxis of thrombosis in patients with high-risk essential thrombocythaemia: an observational study.

Author: Alvarez-Larrán A, Pereira A, Arellano-Rodrigo E, Hernández-Boluda JC, Cervantes F, and Besses C
Subjects: Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prognosis, Risk, Thrombocythemia, Essential mortality, Thrombosis mortality, Treatment Outcome, Young Adult, Antineoplastic Agents therapeutic use, Aspirin administration & dosage, Premedication, Thrombocythemia, Essential complications, Thrombocythemia, Essential drug therapy, Thrombosis etiology, Thrombosis prevention & control
Abstract: The effectiveness of low-dose aspirin in the primary prevention of thrombosis in patients with high-risk essential thrombocythaemia (ET) treated with cytoreductive drugs is not well established. The risk-benefit balance of low-dose aspirin plus cytoreductive therapy compared with cytoreduction alone was retrospectively analysed in 247 patients with high-risk ET without prior thrombosis. Follow-up was 763 and 685 person-years for cytoreduction plus low-dose aspirin and cytoreduction alone, respectively. The rate of thrombosis was not significantly reduced in patients on cytoreduction plus aspirin (14·4 events per 1000 person-years) when compared with those on cytoreduction alone (24·8 events per 1000 person-years; P = 0·2). However, in the subgroup of patients older than 60 years, the addition of low-dose aspirin was associated with a significantly lower rate of thrombosis (8·6 vs. 29·2 thrombosis per 1000 person-years for combined treatment and cytoreduction alone, respectively, P = 0·02). The rate of major bleeding was significantly higher with combined therapy than with cytoreduction alone both in the whole series (14·4 vs. 1·4 haemorrhagic events per 1000 person-years, respectively, P = 0·006) and in the subgroup of patients older than 60 years. In conclusion, low-dose aspirin benefits high-risk ET patients older than 60 years receiving cytoreductive therapy as primary prophylaxis of thrombosis., (© 2013 John Wiley & Sons Ltd.)
Published: 2013
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12. Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia.

Author: Guillem V, Amat P, Cervantes F, Alvarez-Larrán A, Cervera J, Maffioli M, Bellosillo B, Collado M, Marugán I, Martínez-Ruiz F, and Hernández-Boluda JC
Subjects: Adolescent, Adult, Aged, Benzamides, Case-Control Studies, DNA genetics, Female, Genotype, Humans, Imatinib Mesylate, Leukemia, Myeloid, Chronic-Phase diagnosis, Male, Middle Aged, Prognosis, Real-Time Polymerase Chain Reaction, Suppressor of Cytokine Signaling 1 Protein, Young Adult, Antineoplastic Agents therapeutic use, Leukemia, Myeloid, Chronic-Phase drug therapy, Leukemia, Myeloid, Chronic-Phase genetics, Piperazines therapeutic use, Polymorphism, Single Nucleotide genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 22 genetics, Pyrimidines therapeutic use, Suppressor of Cytokine Signaling Proteins genetics
Abstract: The function of the natural modulators of BCR-ABL-induced signaling pathways could influence the results to imatinib treatment. We assessed the association between single nucleotide polymorphisms (SNPs) on genes of the phosphatase family and the suppressors of cytokine signaling and the response to imatinib in 105 patients newly diagnosed with chronic-phase CML. SNPs in SOCS1 (rs243327) and PTPN22 (rs2476601) genes correlated with the risk of primary resistance to imatinib. A high-risk Sokal score, the T allele in PTPN22 SNP, and each copy of the C allele in SOCS1 SNP were adverse prognostic factors for failure-free survival (FFS). Based on such parameters, three risk groups were identified, with the 5-year FFS for each group being 95%, 75%, and 50%, respectively (P<0.001). A simple predictive model including Sokal score and genotype of SOCS1 and PTPN22 SNPs may be useful in the selection of the initial treatment in CML., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
Published: 2012
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13. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet.

Author: Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, Cervantes F, Deininger M, Gratwohl A, Guilhot F, Hochhaus A, Horowitz M, Hughes T, Kantarjian H, Larson R, Radich J, Simonsson B, Silver RT, Goldman J, and Hehlmann R
Subjects: Antineoplastic Agents administration & dosage, Benzamides, Dasatinib, Drug Administration Schedule, Drug Monitoring, Europe, Gene Expression Regulation, Leukemic, Hematopoietic Stem Cell Transplantation, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive enzymology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Piperazines therapeutic use, Protein Kinase Inhibitors administration & dosage, Pyrimidines therapeutic use, Thiazoles therapeutic use, Time Factors, Transplantation, Homologous, Treatment Failure, Treatment Outcome, Antineoplastic Agents therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors therapeutic use
Abstract: Purpose: To review and update the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia with imatinib and second-generation tyrosine kinase inhibitors (TKIs), including monitoring, response definition, and first- and second-line therapy., Methods: These recommendations are based on a critical and comprehensive review of the relevant papers up to February 2009 and the results of four consensus conferences held by the panel of experts appointed by ELN in 2008., Results: Cytogenetic monitoring was required at 3, 6, 12, and 18 months. Molecular monitoring was required every 3 months. On the basis of the degree and the timing of hematologic, cytogenetic, and molecular results, the response to first-line imatinib was defined as optimal, suboptimal, or failure, and the response to second-generation TKIs was defined as suboptimal or failure., Conclusion: Initial treatment was confirmed as imatinib 400 mg daily. Imatinib should be continued indefinitely in optimal responders. Suboptimal responders may continue on imatinb, at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.
Published: 2009
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14. Epigenetic down-regulation of BIM expression is associated with reduced optimal responses to imatinib treatment in chronic myeloid leukaemia.

Author: San José-Eneriz E, Agirre X, Jiménez-Velasco A, Cordeu L, Martín V, Arqueros V, Gárate L, Fresquet V, Cervantes F, Martínez-Climent JA, Heiniger A, Torres A, Prósper F, and Roman-Gomez J
Subjects: Adult, Antineoplastic Combined Chemotherapy Protocols pharmacology, Apoptosis drug effects, Apoptosis Regulatory Proteins genetics, Azacitidine analogs & derivatives, Azacitidine pharmacology, Bcl-2-Like Protein 11, Benzamides, Cell Proliferation drug effects, DNA Methylation, DNA Modification Methylases antagonists & inhibitors, Decitabine, Dose-Response Relationship, Drug, Down-Regulation drug effects, Drug Evaluation, Preclinical methods, Drug Resistance, Neoplasm genetics, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic drug effects, Gene Expression Regulation, Neoplastic genetics, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Membrane Proteins genetics, Middle Aged, Promoter Regions, Genetic genetics, Proto-Oncogene Proteins genetics, RNA, Messenger genetics, RNA, Neoplasm genetics, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Apoptosis Regulatory Proteins biosynthesis, Down-Regulation genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Membrane Proteins biosynthesis, Piperazines pharmacology, Proto-Oncogene Proteins biosynthesis, Pyrimidines pharmacology
Abstract: Background: Expression of the pro-apoptotic BCL-2-interacting mediator (BIM) has recently been implicated in imatinib-induced apoptosis of BCR-ABL1(+) cells. However, the mechanisms involved in the regulation of BIM in CML and its role in the clinical setting have not been established., Design and Methods: We analysed the mRNA expression of BIM in 100 newly diagnosed patients with CML in chronic phase by Q-RT-PCR and the protein levels by Western blot analysis. Methylation status was analysed by bisulphite genomic sequencing and MSP. CML cell lines were treated with imatinib and 5-aza-2'-deoxycytidine, and were transfected with two different siRNAs against BIM and cell proliferation and apoptosis were analysed., Results: We demonstrated that down-regulation of BIM expression was present in 36% of the patients and was significantly associated with a lack of optimal response to imatinib as indicated by the decrease in cytogenetic and molecular responses at 6, 12 and 18 months in comparison with patients with normal BIM expression (p<0.05). Expression of BIM was mediated by promoter hypermethylation as demonstrated by restoration of BIM expression after treatment of CML cells with 5-aza-2'-deoxycytidine. Using CML cell lines with low and normal expression of BIM we further demonstrated that the expression of BIM is required for imatinib-induced CML apoptosis., Conclusion: Our data indicate that down-regulation of BIM is epigenetically controlled by methylation in a percentage of CML patients and has an unfavourable prognostic impact, and that the combination of imatinib with a de-methylating agent may result in improved responses in patients with decreased expression of BIM.
Published: 2009
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15. [Chronic myeloid leukemia 2008].

Author: Cervantes F
Subjects: Antineoplastic Agents administration & dosage, Benzamides, Clinical Trials as Topic, Clinical Trials, Phase II as Topic, Dasatinib, Follow-Up Studies, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Multicenter Studies as Topic, Piperazines administration & dosage, Piperazines therapeutic use, Protein Kinase Inhibitors administration & dosage, Protein-Tyrosine Kinases antagonists & inhibitors, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Thiazoles administration & dosage, Thiazoles therapeutic use, Time Factors, Treatment Outcome, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Protein Kinase Inhibitors therapeutic use
Published: 2008
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16. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia.

Author: Lee SJ, Kukreja M, Wang T, Giralt SA, Szer J, Arora M, Woolfrey AE, Cervantes F, Champlin RE, Gale RP, Halter J, Keating A, Marks DI, McCarthy PL, Olavarria E, Stadtmauer EA, Abecasis M, Gupta V, Khoury HJ, George B, Hale GA, Liesveld JL, Rizzieri DA, Antin JH, Bolwell BJ, Carabasi MH, Copelan E, Ilhan O, Litzow MR, Schouten HC, Zander AR, Horowitz MM, and Maziarz RT
Subjects: Adolescent, Adult, Aged, Benzamides, Child, Child, Preschool, Disease-Free Survival, Female, HLA Antigens metabolism, Humans, Imatinib Mesylate, Male, Middle Aged, Registries, Treatment Outcome, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Piperazines therapeutic use, Pyrimidines therapeutic use
Abstract: Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM(+)) and 900 subjects who did not receive IM before HCT (IM(-)) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM(+) and IM(-) groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.
Published: 2008
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17. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.

Author: Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, and Larson RA
Subjects: Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzamides, Cytarabine administration & dosage, Disease-Free Survival, Female, Follow-Up Studies, Fusion Proteins, bcr-abl blood, Humans, Imatinib Mesylate, Interferon-alpha administration & dosage, Kaplan-Meier Estimate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Piperazines adverse effects, Pyrimidines adverse effects, Survival Analysis, Survival Rate, Treatment Outcome, Antineoplastic Agents therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines therapeutic use, Protein-Tyrosine Kinases antagonists & inhibitors, Pyrimidines therapeutic use
Abstract: Background: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy., Methods: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events., Results: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events., Conclusions: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].), (Copyright 2006 Massachusetts Medical Society.)
Published: 2006
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18. Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia.

Author: Pou M, Saval N, Vera M, Saurina A, Solé M, Cervantes F, and Botey A
Subjects: Antineoplastic Agents administration & dosage, Benzamides, Enzyme Inhibitors administration & dosage, Female, Humans, Imatinib Mesylate, Middle Aged, Piperazines administration & dosage, Protein-Tyrosine Kinases antagonists & inhibitors, Pyrimidines administration & dosage, Acute Kidney Injury chemically induced, Antineoplastic Agents adverse effects, Enzyme Inhibitors adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines adverse effects, Pyrimidines adverse effects
Abstract: A 58-year-old woman with chronic myeloid leukemia (CML), and previous intolerance to interferon was treated with the BCR-ABL tyrosine kinase protein inhibitor imatinib mesylate. Coincidentally, with the start of treatment, the patient developed acute renal failure, with acute tubular necrosis being observed on histopathology. Imatinib was stopped and three hemodialysis sessions were performed, which was followed by a progressive improvement of the renal function and normalization of the urine output. One year later the patient still has mild chronic renal failure and remains in chronic phase of CML on hydroxyurea treatment.
Published: 2003
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19. Cadherin-13, a mediator of calcium-dependent cell-cell adhesion, is silenced by methylation in chronic myeloid leukemia and correlates with pretreatment risk profile and cytogenetic response to interferon alfa.

Author: Roman-Gomez J, Castillejo JA, Jimenez A, Cervantes F, Boque C, Hermosin L, Leon A, Grañena A, Colomer D, Heiniger A, and Torres A
Subjects: Adult, Cadherins genetics, Female, Gene Expression Regulation, Neoplastic drug effects, Genes, Tumor Suppressor, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Male, Methylation drug effects, Middle Aged, Multivariate Analysis, Polymerase Chain Reaction, Predictive Value of Tests, Prognosis, Promoter Regions, Genetic, Proportional Hazards Models, RNA, Messenger metabolism, Risk Factors, Survival Analysis, Antineoplastic Agents pharmacology, Cadherins metabolism, Calcium metabolism, Gene Silencing drug effects, Interferon-alpha pharmacology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism
Abstract: Purpose: Cadherin-13 (CDH13) is a newly characterized cadherin molecule responsible for selective cell recognition and adhesion, the expression of which is decreased by methylation in a variety of human cancers, indicating that the CDH13 gene functions as a tumor suppressor gene. Although defective progenitor-stromal adhesion is a well-recognized feature of chronic myeloid leukemia (CML), the role of CDH13 abnormalities has not been evaluated in this disease., Patients and Methods: We examined the methylation status of the CDH13 promoter in 179 chronic phase (CP)-CML patients and in 52 advanced-phase samples and correlated it with mRNA expression using methylation-specific polymerase chain reaction (PCR) and reverse transcriptase PCR., Results: Aberrant de novo methylation of the CDH13 promoter region was observed in 99 (55%) of 179 of CP-CML patients, and 90 of the patients failed to express CDH13 mRNA (P <.0001). Advanced-stage samples (n = 52) showed concordant methylation results with their corresponding CP tumors, indicating that CDH13 methylation was not acquired during the course of the disease. Nevertheless, absence of CDH13 expression was more frequently observed among Sokal high-risk patients (P =.01) and was also independently associated with a shorter median progression-free survival time (P =.03) and poor cytogenetic response to interferon alfa treatment (P =.0001)., Conclusion: Our data indicate that the silencing of CDH13 expression by aberrant promoter methylation occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.
Published: 2003
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20. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.

Author: O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, and Druker BJ
Subjects: Adolescent, Adult, Aged, Antineoplastic Agents administration & dosage, Benzamides, Cytarabine administration & dosage, Disease Progression, Female, Humans, Imatinib Mesylate, Interferon-alpha administration & dosage, Leukemia, Myeloid, Chronic-Phase mortality, Male, Middle Aged, Prospective Studies, Survival Rate, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Chronic-Phase drug therapy, Piperazines therapeutic use, Pyrimidines therapeutic use
Abstract: Background: Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML., Methods: We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression., Results: After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy., Conclusions: In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML., (Copyright 2003 Massachusetts Medical Society)
Published: 2003
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21. Imatinib mesylate (STI571) treatment in patients with chronic-phase chronic myelogenous leukaemia previously submitted to autologous stem cell transplantation.

Author: Cervantes F, Hernández-Boluda JC, Odriozola J, Camós M, Villalón L, Martínez-Climent JA, del Campo R, García-Conde J, and Montserrat E
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Benzamides, Disease-Free Survival, Female, Humans, Imatinib Mesylate, Interferons therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Leukemia, Myeloid, Chronic-Phase therapy, Male, Middle Aged, Treatment Failure, Treatment Outcome, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myeloid, Chronic-Phase drug therapy, Piperazines therapeutic use, Pyrimidines therapeutic use
Abstract: Imatinib mesylate (STI571) is a highly effective and well-tolerated treatment for patients with chronic-phase chronic myeloid leukaemia (CML), but information on its efficacy and tolerance in intensively pretreated patients is scarce. Thirty-three chronic-phase CML patients who were resistant or intolerant to interferon (IFN) and had been previously submitted to autologous stem cell transplantation were treated with imatinib for a median of 14 months (range: 6-19 months). Seven patients were in haematological response (HR) at the start of treatment; the remaining 26 attained a HR at a median of 3 weeks (range: 1-4 weeks). Major cytogenetic response rates at 3, 6 and 12 months were 42%, 45% and 55%, respectively, including 21%, 24% and 33% complete responses. Grade 3-4 neutropenia, thrombocytopenia and anaemia developed in 33%, 27% and 12% of patients respectively. Non-haematological toxicity included superficial oedema (21% of patients), gastrointestinal symptoms (18%), muscle cramps (15%), skin rash and liver enzyme increase (3% each). These results were not significantly different from those in 65 chronic-phase CML patients, resistant or intolerant to interferon without a previous ASCT, who were included in the same protocol. Imatinib mesylate is effective and safe in chronic-phase CML patients with a previous history of intensive treatment.
Published: 2003
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22. Imatinib mesylate (Gleevec, Glivec): a new therapy for chronic myeloid leukemia and other malignancies.

Author: Hernández-Boluda JC and Cervantes F
Subjects: Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Benzamides, Biological Availability, Clinical Trials as Topic, Half-Life, Humans, Imatinib Mesylate, Intestinal Absorption, Leukemia, Myelogenous, Chronic, BCR-ABL Positive etiology, Piperazines adverse effects, Piperazines pharmacokinetics, Pyrimidines adverse effects, Pyrimidines pharmacokinetics, Antineoplastic Agents therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Primary Myelofibrosis drug therapy, Pyrimidines therapeutic use
Abstract: Imatinib mesylate (STI571, Gleevec, Glivec, a selective inhibitor of the BCR-ABL tyrosine kinase causative of chronic myeloid leukemia (CML), represents the paradigm of how a better understanding of the pathogenetic mechanisms of a neoplastic disease can lead to the development of a targeted molecular therapy. Phase II clinical trials have shown marked therapeutic activity of imatinib in all evolutive phases of CML, but notably in the chronic phase, where it induces complete hematological responses in almost 100% of patients resistant or intolerant to interferon, with a major cytogenetic response rate of 60%, including 41% complete cytogenetic responses. The preliminary results of an ongoing phase III multicenter randomized study comparing imatinib with interferon plus cytarabine as first-line treatment for CML favor imatinib in terms of efficacy and safety. If confirmed with longer follow-up,these results would establish imatinib as the choice therapy for the majority of CML patients, with allogeneic transplantation being restricted as initial therapy only to younger patients with a family donor. Longer follow-up will answer some questions, such as those on long-term safety, durability of the responses, whether these will translate into a survival prolongation and the possibility of molecular responses. In addition, further information on the mechanisms involved in the primary and acquired resistance to imatinib is needed. Besides the Bcr-Abl protein, the drug is also active against other tyrosine kinases, such as Abl, the stem-cell factor receptor (c-kit) and the platelet-derived growth factor receptor, whose inhibition might have potential implications for the treatment of several malignancies. In this sense, it must be pointed out that imatinib has shown a remarkable activity in gastrointestinal stromal tumors., (Copyright 2002 Prous Science)
Published: 2002
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23. Progressive multifocal leukoencephalopathy following oral fludarabine treatment of chronic lymphocytic leukemia.

Author: Cid J, Revilla M, Cervera A, Cervantes F, Muñoz E, Ferrer I, and Montserrat E
Subjects: Administration, Oral, Biopsy methods, Brain pathology, Humans, Male, Middle Aged, Stereotaxic Techniques, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukoencephalopathy, Progressive Multifocal chemically induced, Vidarabine adverse effects, Vidarabine analogs & derivatives, Vidarabine therapeutic use
Abstract: Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disorder of the central nervous system usually affecting immunocompromised individuals and is due to infection of the oligodendrocytes by the JC virus. A case of PML in a chronic lymphocytic leukemia (CLL) patient treated with fludarabine is reported, representing the second such instance in which the diagnosis of the neurological disorder was established by brain biopsy. A 61-year-old man with a 14-year history of B-cell type CLL, for which he had received chlorambucil therapy 10 years earlier, developed progressive paresis of both left extremities at 7 months of receiving low doses of oral fludarabine, when his CD4 count has decreased to 0.08 x 10(9)/l. Cranial magnetic resonance imaging revealed a subcortical focal lesion at the right precentral gyrus and a focal lesion at the right thalamus, and a stereotactic brain biopsy showed pathological findings consistent with PML, namely severe myelin breakdown, reactive astrocytosis, and abnormal, huge glial cells with large bizarre nuclei showing granular basophilic inclusions, whereas the presence of the JC virus was demonstrated by in situ hybridization. The present case, in addition to a few previously reported, calls attention to the possibility that severe neurological side effects can be associated with the immunosuppression provoked by the use of fludarabine in CLL patients.
Published: 2000
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24. Chronic systemic candidiasis in acute leukemia.

Author: Blade, J., Lopez-Guillermo, A., Rozman, C., Grañena, A., Bruguera, M., Bordas, J., Cervantes, F., Carreras, E., Sierra, J., Montserrat, E., and Grañena, A
Subjects: CANDIDA diagnosis, AMPHOTERICIN B, FLUCONAZOLE, ANTINEOPLASTIC agents, CANDIDIASIS, CHRONIC diseases, LYMPHOBLASTIC leukemia, ACUTE myeloid leukemia, TREATMENT effectiveness, DISEASE complications, THERAPEUTICS
Abstract: In the past few years a new syndrome of invasive Candida infection, the so-called hepatosplenic or chronic systemic candidiasis (CSC), has been recognized with increasing frequency in neutropenic patients. From January 1985 to December 1990, ten of 305 acute leukemia (AL) patients treated at our institution were diagnosed as having CSC. In contrast, during the same period this type of Candida infection was not observed in any patient with hematological diseases other than AL treated in our center, including 277 patients who underwent bone marrow transplantation. All patients with CSC had fever and hepatomegaly, and five complained of abdominal pain. Seven patients had neutrophilic leukocytosis and six an increased serum alkaline phosphatase activity. Abdominal computed tomography and ultrasound study showed typical lesions in eight and seven patients, respectively. In four patients a laparoscopy-guided needle liver biopsy displayed yellowish nodules on the liver surface, and the histologic study revealed large granulomas with yeasts and pseudohyphae. All patients were given amphotericin B (mean: 4.6 g, range: 1-12.5 g) and 5-fluorocytosine, and five received fluconazole. No patient died as a direct consequence of CSC and in six the infection resolved. Finally, once controlled, the infectious complication did not preclude subsequent intensive antileukemic therapy, including bone marrow transplantation. [ABSTRACT FROM AUTHOR]
Published: 1992
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25. Fludarabine for prolymphocytic leukaemia and risk of interstitial pneumonitis.

Author: Cervantes, F, Salgado, C, Montserrat, E, and Rozman, C
Subjects: *ADENOSINES, *ANTIMETABOLITES, *ANTINEOPLASTIC agents, *B cells, *CHRONIC lymphocytic leukemia, *PULMONARY fibrosis
Published: 1990
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26. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Author: Simona Soverini, Jeffrey H. Lipton, Richard A. Larson, Dietger Niederwieser, Andrey Zaritskey, Fabrizio Pane, Francois-Xavier Mahon, Jeroen Janssen, Richard E. Clark, François Guilhot, Juan Luis Steegmann, Jerald P. Radich, Michael W. Deininger, Andreas Hochhaus, Richard T. Silver, Susanne Saußele, Johan Richter, Timothy P. Hughes, Jane F. Apperley, Jiří Mayer, Henrik Hjorth-Hansen, Hagop M. Kantarjian, Jorge E. Cortes, Anna G. Turkina, Michele Baccarani, Gianantonio Rosti, Franck E. Nicolini, Philippe Rousselot, Giuseppe Saglio, Delphine Rea, Dong-Wook Kim, Ruediger Hehlmann, Charles A. Schiffer, Francisco Cervantes, Hochhaus A., Baccarani M., Silver R.T., Schiffer C., Apperley J.F., Cervantes F., Clark R.E., Cortes J.E., Deininger M.W., Guilhot F., Hjorth-Hansen H., Hughes T.P., Janssen J.J.W.M., Kantarjian H.M., Kim D.W., Larson R.A., Lipton J.H., Mahon F.X., Mayer J., Nicolini F., Niederwieser D., Pane F., Radich J.P., Rea D., Richter J., Rosti G., Rousselot P., Saglio G., Saussele S., Soverini S., Steegmann J.L., Turkina A., Zaritskey A., Hehlmann R., Hochhaus, A., Baccarani, M., Silver, R. T., Schiffer, C., Apperley, J. F., Cervantes, F., Clark, R. E., Cortes, J. E., Deininger, M. W., Guilhot, F., Hjorth-Hansen, H., Hughes, T. P., Janssen, J. J. W. M., Kantarjian, H. M., Kim, D. W., Larson, R. A., Lipton, J. H., Mahon, F. X., Mayer, J., Nicolini, F., Niederwieser, D., Pane, F., Radich, J. P., Rea, D., Richter, J., Rosti, G., Rousselot, P., Saglio, G., Saussele, S., Soverini, S., Steegmann, J. L., Turkina, A., Zaritskey, A., Hehlmann, R., Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Bergonié [Bordeaux], UNICANCER, Centre Léon Bérard [Lyon], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Novartis Berlin Mathematical School, BMS Daiichi-Sankyo Janssen Pharmaceuticals Angelini Pharma Pfizer, The ELN panel for recommendations in CML comprises 34 experts from Europe, America, and the Asian-Pacific areas. The panel met six times at international meetings of the American Society of Hematology (2015, 2016), the European School of Hematology (2017), the ELN (2019), the European Investigators on CML (2019), and the European School of Hematology/International CML Foundation (2019). Five sets of key questions were submitted to panel members to complement the meetings. Discordant opinions were harmonized by email discussions, and a consensus of 75–100% was reached in most, but not all instances. Unresolved controversies are described in the discussion section. The costs of the meetings and the preparation of the interim and final reports were born entirely by ELN, a research network of excellence initiated by the European Union, now funded by donations and projects of ELN participants. There was no financial support from industry for any activity. Treatment recommendations are limited to the TKIs that have been approved with at least one indication in CML, either by the US Federal Drug Administration (FDA) or/and by the European Medicine Agency (EMA). The drugs are listed in the order of FDA approval. The panel acknowledges that not all drugs may be available worldwide and that the high price of some makes access to these drugs problematic in some countries., Conflict of interest Members of the expert panel declare the following potential conflicts of interest: AH, Research support: Novartis, BMS, MSD, Pfizer, Incyte. Honoraria: Novartis, BMS, Pfizer, Incyte, Takeda, Fusion Pharma. MB, Honoraria: Novartis, BMS, Pfizer, Incyte, Ariad, Takeda, Fusion Pharma. Logistic support: Novartis, BMS, Pfizer, Incyte, Ariad. CS, Research support: Ariad. Honoraria: Novartis, Teva, Pfizer, Juno, Astellas, Ambit. JFA, Research support: Incyte, Novartis, Pfizer. Honoraria: Incyte, Novartis, Pfizer, BMS. FC, Honoraria: Novartis, BMS, Pfizer, Incyte, Celgene, Italfarmaco. Travel grants: BMS, Celgene. REC, Research support: Novartis, Pfizer, BMS. Honoraria: Novartis, Pfizer, BMS, Ariad/Incyte, Jazz, Abbvie. JEC, Research support: BMS, Novartis, Pfizer, Sun Pharma, Takeda. Honoraria: Novartis, Pfizer, Takeda. MWD, Research support: Takeda, Novartis, Pfizer, Incyte, SPARC, TetraLogic Pharmaceuticals, Blueprint. Honoraria: Blueprint, Fusion Pharma, Novartis, Sangamo, Ascentage Pharma, Adelphi, CTI, BMS, Pfizer, Takeda, Medscape, Incyte, Humana, TRM, Ariad, Galena Biopharma. FG, Research support: Novartis, Roche. Honoraria: Novartis, BMS, Celgene. HHH, Research support: Pfizer, BMS, Merck, Austrian Orphan Pharma, Nordic Cancer Union. Honoraria: Pfizer, Incyte, Austrian Orphan Pharma. TPH, Research support: Novartis, BMS, Celgene. Honoraria: Novartis, BMS, Fusion Pharma. Travel grants: Novartis. JJ, Research support: Novartis, BMS. President, Apps for Care and Science, nonprofit foundation supported by Daiichi-Sankyo, Janssen, Incyte, BMS, Servier, Jazz, Celgene. Honoraria: Abbvie, Novartis, Pfizer, Incyte. HMK, Research support: AbbVie, Agios, Amgen, Ariad, Astex, BMS, Cyclacel, Daiichi-Sankyo, Immunogen, Jazz Pharma, Novartis, Pfizer. Honoraria: AbbVie, Actinium, Agios, Amgen, Immunogen, Pfizer, Takeda. DWK, Research support: Novartis, Pfizer, BMS, Takeda, Il-Yang Co. Honoraria: Novartis, BMS, Otsuka, Il-Yang Co. RAL, Research support: Astellas, Celgene, Cellectis, Daiichi Sankyo, Novartis, Rafael Pharmaceuticals. Honoraria: Amgen, Celgene, CVS Caremark, Epizyme, Novartis, Takeda. JHL, Research support and honoraria: Novartis, BMS, Pfizer, Takeda. FXM, Research support and honoraria: Novartis. Travel grants: Celgene, Pfizer, Astra Zeneca. JM, Research support: Angelini, Pfizer, Novartis, BMS. Travel grants: Novartis. FN, Research support: Novartis, Incyte. Honoraria: Incyte biosciences, Novartis, BMS, Sun Pharma. Travel grants: Incyte biosciences, Novartis, BMS. DN, Research support: Daiichi, Honoraria: Cellectis. Travel grants: EUSA, Novartis, and Amgen. FP, Research support: Novartis. Honoraria: Novartis, BMS, Pfizer, Incyte. JPR, Research support: Novartis. Honoraria: Novartis, BMS, Ariad, Amgen, Takeda, Cepheid, Bio-Rad, Adaptive, Seagen, Gilead. DR, Honoraria: BMS, Novartis, Pfizer, Incyte. JR, Honoraria: Novartis, Pfizer. GR, Research support, honoraria, and travel grants: Novartis, BMS, Incyte, Pfizer, Roche. PR, Research support: Incyte, Pfizer. Honoraria: BMS, Incyte, Pfizer, Novartis. GS, Honoraria: Novartis, BMS, Incyte, Pfizer. SiS, Honoraria: Incyte. SuS, Research support: BMS, Incyte, Novartis. Honoraria: BMS, Incyte, Novartis, Pfizer. Travel grants: BMS, Incyte, Novartis. JLS, Research support, honoraria, and travel grants: BMS, Incyte, Novartis, Pfizer. AT, Honoraria: BMS, Novartis, Pfizer, Fusion Pharma. Travel grants: BMS, Novartis, Pfizer. AZ, Research support: Novartis, Celgene, Janssen. Travel grants: Novartis. RTS, RH, none.
Subjects: Oncology, Cancer Research, Consensus Development Conferences as Topic, Dasatinib, Fusion Proteins, bcr-abl, Quinoline, Gene Expression, Review Article, Tyrosine-kinase inhibitor, Antineoplastic Agent, European LeukemiaNet, 0302 clinical medicine, hemic and lymphatic diseases, 0303 health sciences, Aniline Compounds, Myeloid leukemia, Disease Management, Hematology, Aniline Compound, 3. Good health, 030220 oncology & carcinogenesis, Quinolines, Imatinib Mesylate, Bosutinib, Nitrile, medicine.drug, Human, medicine.medical_specialty, medicine.drug_class, Clinical Decision-Making, Protein Kinase Inhibitor, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Targeted therapies, Life Expectancy, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Nitriles, medicine, Humans, Protein Kinase Inhibitors, Chronic myeloid leukaemia, 030304 developmental biology, Monitoring, Physiologic, business.industry, Imatinib, Survival Analysis, Discontinuation, Pyrimidines, Nilotinib, Pyrimidine, Quality of Life, business
Abstract: The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
Published: 2020
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27. The European Hematology Association Roadmap for European Hematology Research: a consensus document

Author: Engert, Andreas, Balduini, Carlo, Brand, Anneke, Coiffier, Bertrand, Cordonnier, Catherine, Doehner, Hartmut, de Wit, Thom Duyvene, Eichinger, Sabine, Fibbe, Willem, Green, Tony, de Haas, Fleur, Iolascon, Achille, Jaffredo, Thierry, Rodeghiero, Francesco, Salles, Gilles, Schuringa, Jan Jacob, Andre, Marc, Andre-Schmutz, Isabelle, Bacigalupo, Andrea, Bochud, Pierre-Yves, den Boer, Monique, Bonini, Chiara, Camaschella, Clara, Cant, Andrew, Cappellini, Maria Domenica, Cazzola, Mario, Lo Celso, Cristina, Dimopoulos, Meletios, Douay, Luc, Dzierzak, Elaine, Einsele, Hermann, Ferreri, Andres, De Franceschi, Lucia, Gaulard, Philippe, Gottgens, Berthold, Greinacher, Andreas, Gresele, Paolo, Gribben, John, de Haan, Gerald, Hansen, John-Bjarne, Hochhaus, Andreas, Kadir, Rezan, Kaveri, Srini, Kouskoff, Valerie, Kuehne, Thomas, Kyrle, Paul, Ljungman, Per, Maschmeyer, Georg, Mendez-Ferrer, Simon, Milsom, Michael, Mummery, Christine, Ossenkoppele, Gert, Pecci, Alessandro, Peyvandi, Flora, Philipsen, Sjaak, Reitsma, Pieter, Maria Ribera, Jose, Risitano, Antonio, Rivella, Stefano, Ruf, Wolfram, Schroeder, Timm, Scully, Marie, Socie, Gerard, Staal, Frank, Stanworth, Simon, Stauder, Reinhard, Stilgenbauer, Stephan, Tamary, Hannah, Theilgaard-Monch, Kim, Thein, Swee Lay, Tilly, Herve, Trneny, Marek, Vainchenker, William, Vannucchi, Alessandro Maria, Viscoli, Claudio, Vrielink, Hans, Zaaijer, Hans, Zanella, Alberto, Zolla, Lello, Zwaginga, Jaap Jan, Martinez, Patricia Aguilar, van den Akker, Emile, Allard, Shubha, Anagnou, Nicholas, Andolfo, Immacolata, Andrau, Jean-Christophe, Angelucci, Emanuele, Anstee, David, Aurer, Igor, Avet-Loiseau, Herve, Aydinok, Yesim, Bakchoul, Tamam, Balduini, Alessandra, Barcellini, Wilma, Baruch, Dominique, Baruchel, Andre, Bayry, Jagadeesh, Bento, Celeste, van den Berg, Anke, Bernardi, Rosa, Bianchi, Paola, Bigas, Anna, Biondi, Andrea, Bohonek, Milos, Bonnet, Dominique, Borchmann, Peter, Borregaard, Niels, Braekkan, Sigrid, van den Brink, Marcel, Brodin, Ellen, Bullinger, Lars, Buske, Christian, Butzeck, Barbara, Cammenga, Jorg, Campo, Elias, Carbone, Antonino, Cervantes, Francisco, Cesaro, Simone, Charbord, Pierre, Claas, Frans, Cohen, Hannah, Conard, Jacqueline, Coppo, Paul, Vives Corrons, Joan-Lluis, da Costa, Lydie, Davi, Frederic, Delwel, Ruud, Dianzani, Irma, Domanovic, Dragoslav, Donnelly, Peter, Drnovsek, Tadeja Dovc, Dreyling, Martin, Du, Ming-Qing, Dufour, Carlo, Durand, Charles, Efremov, Dimitar, Eleftheriou, Androulla, Elion, Jacques, Emonts, Marieke, Engelhardt, Monika, Ezine, Sophie, Falkenburg, Fred, Favier, Remi, Federico, Massimo, Fenaux, Pierre, Fitzgibbon, Jude, Flygare, Johan, Foa, Robin, Forrester, Lesley, Galacteros, Frederic, Garagiola, Isabella, Gardiner, Chris, Garraud, Olivier, van Geet, Christel, Geiger, Hartmut, Geissler, Jan, Germing, Ulrich, Ghevaert, Cedric, Girelli, Domenico, Godeau, Bertrand, Goekbuget, Nicola, Goldschmidt, Hartmut, Goodeve, Anne, Graf, Thomas, Graziadei, Giovanna, Griesshammer, Martin, Gruel, Yves, Guilhot, Francois, von Gunten, Stephan, Gyssens, Inge, Halter, Jorg, Harrison, Claire, Harteveld, Cornelis, Hellstrom-Lindberg, Eva, Hermine, Olivier, Higgs, Douglas, Hillmen, Peter, Hirsch, Hans, Hoskin, Peter, Huls, Gerwin, Inati, Adlette, Johnson, Peter, Kattamis, Antonis, Kiefel, Volker, Kleanthous, Marina, Klump, Hannes, Krause, Daniela, Hovinga, Johanna Kremer, Lacaud, Georges, Lacroix-Desmazes, Sebastien, Landman-Parker, Judith, LeGouill, Steven, Lenz, Georg, von Lilienfeld-Toal, Marie, von Lindern, Marieke, Lopez-Guillermo, Armando, Lopriore, Enrico, Lozano, Miguel, MacIntyre, Elizabeth, Makris, Michael, Mannhalter, Christine, Martens, Joost, Mathas, Stephan, Matzdorff, Axel, Medvinsky, Alexander, Menendez, Pablo, Migliaccio, Anna Rita, Miharada, Kenichi, Mikulska, Malgorzata, Minard, Veronique, Montalban, Carlos, de Montalembert, Mariane, Montserrat, Emili, Morange, Pierre-Emmanuel, Mountford, Joanne, Muckenthaler, Martina, Mueller-Tidow, Carsten, Mumford, Andrew, Nadel, Bertrand, Navarro, Jose-Tomas, el Nemer, Wassim, Noizat-Pirenne, France, O'Mahony, Brian, Oldenburg, Johannes, Olsson, Martin, Oostendorp, Robert, Palumbo, Antonio, Passamonti, Francesco, Patient, Roger, de Latour, Regis Peffault, Pflumio, Francoise, Pierelli, Luca, Piga, Antonio, Pollard, Debra, Raaijmakers, Marc, Radford, John, Rambach, Ralf, Rao, A. Koneti, Raslova, Hana, Rebulla, Paolo, Rees, David, Ribrag, Vincent, Rijneveld, Anita, Rinalducci, Sara, Robak, Tadeusz, Roberts, Irene, Rodrigues, Charlene, Rosendaal, Frits, Rosenwald, Andreas, Rule, Simon, Russo, Roberta, Saglio, Guiseppe, Sanchez, Mayka, Scharf, Ruediger E., Schlenke, Peter, Semple, John, Sierra, Jorge, So-Osman, Cynthia, Manuel Soria, Jose, Stamatopoulos, Kostas, Stegmayr, Bernd, Stunnenberg, Henk, Swinkels, Dorine, Taborda Barata, Joao Pedro, Taghon, Tom, Taher, Ali, Terpos, Evangelos, Thachil, Jecko, Tissot, Jean Daniel, Touw, Ivo, Toye, Ash, Trappe, Ralf, Traverse-Glehen, Alexandra, Unal, Sule, Vaulont, Sophie, Viprakasit, Vip, Vitolo, Umberto, van Wijk, Richard, Wojtowicz, Agnieszka, Zeerleder, Sacha, Zieger, Barbara, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Sorbonne Paris Cité (USPC), Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital of Cologne [Cologne], Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Department of Internal Medicine I, Medizinische Universität Wien = Medical University of Vienna, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ege Üniversitesi, Engert, Andrea, Balduini, Carlo, Brand, Anneke, Coiffier, Bertrand, Cordonnier, Catherine, Döhner, Hartmut, De Wit, Thom Duyvené, Eichinger, Sabine, Fibbe, Willem, Green, Tony, De Haas, Fleur, Iolascon, Achille, Jaffredo, Thierry, Rodeghiero, Francesco, Sall Es, Gille, Schuringa, Jan Jacob, André, Marc, Andre Schmutz, Isabelle, Bacigalupo, Andrea, Bochud, Pierre Yve, Den Boer, Monique, Bonini, Chiara, Camaschella, Clara, Cant, Andrew, Cappellini, Maria Domenica, Cazzola, Mario, Celso, Cristina Lo, Dimopoulos, Meletio, Douay, Luc, Dzierzak, Elaine, Einsele, Hermann, Ferreri, André, De Franceschi, Lucia, Gaulard, Philippe, Gottgens, Berthold, Greinacher, Andrea, Gresele, Paolo, Gribben, John, De Haan, Gerald, Hansen, John Bjarne, Hochhaus, Andrea, Kadir, Rezan, Kaveri, Srini, Kouskoff, Valerie, Kühne, Thoma, Kyrle, Paul, Ljungman, Per, Maschmeyer, Georg, Méndez Ferrer, Simón, Milsom, Michael, Mummery, Christine, Ossenkoppele, Gert, Pecci, Alessandro, Peyvandi, Flora, Philipsen, Sjaak, Reitsma, Pieter, Ribera, José Maria, Risitano, ANTONIO MARIA, Rivella, Stefano, Ruf, Wolfram, Schroeder, Timm, Scully, Marie, Socie, Gerard, Staal, Frank, Stanworth, Simon, Stauder, Reinhard, Stilgenbauer, Stephan, Tamary, Hannah, Theilgaard Mönch, Kim, Thein, Swee Lay, Tilly, Hervé, Trneny, Marek, Vainchenker, William, Vannucchi, Alessandro Maria, Viscoli, Claudio, Vrielink, Han, Zaaijer, Han, Zanella, Alberto, Zolla, Lello, Zwaginga, Jaap Jan, Martinez, Patricia Aguilar, Van Den Akker, Emile, Allard, Shubha, Anagnou, Nichola, Andolfo, Immacolata, Andrau, Jean Christophe, Angelucci, Emanuele, Anstee, David, Aurer, Igor, Avet Loiseau, Hervé, Aydinok, Yesim, Bakchoul, Tamam, Balduini, Alessandra, Barcellini, Wilma, Baruch, Dominique, Baruchel, André, Bayry, Jagadeesh, Bento, Celeste, Van Den Berg, Anke, Bernardi, Rosa, Bianchi, Paola, Bigas, Anna, Biondi, Andrea, Bohonek, Milo, Bonnet, Dominique, Borchmann, Peter, Borregaard, Niel, Brækkan, Sigrid, Van Den Brink, Marcel, Brodin, Ellen, Bullinger, Lar, Buske, Christian, Butzeck, Barbara, Cammenga, Jörg, Campo, Elia, Carbone, Antonino, Cervantes, Francisco, Cesaro, Simone, Charbord, Pierre, Claas, Fran, Cohen, Hannah, Conard, Jacqueline, Coppo, Paul, Vives Corron, Joan Llui, Da Costa, Lydie, Davi, Frederic, Delwel, Ruud, Dianzani, Irma, Domanović, Dragoslav, Donnelly, Peter, Drnovšek, Tadeja Dovč, Dreyling, Martin, Du, Ming Qing, Dufour, Carlo, Durand, Charle, Efremov, Dimitar, Eleftheriou, Androulla, Elion, Jacque, Emonts, Marieke, Engelhardt, Monika, Ezine, Sophie, Falkenburg, Fred, Favier, Remi, Federico, Massimo, Fenaux, Pierre, Fitzgibbon, Jude, Flygare, Johan, Foà, Robin, Forrester, Lesley, Galacteros, Frederic, Garagiola, Isabella, Gardiner, Chri, Garraud, Olivier, Van Geet, Christel, Geiger, Hartmut, Geissler, Jan, Germing, Ulrich, Ghevaert, Cedric, Girelli, Domenico, Godeau, Bertrand, Gökbuget, Nicola, Goldschmidt, Hartmut, Goodeve, Anne, Graf, Thoma, Graziadei, Giovanna, Griesshammer, Martin, Gruel, Yve, Guilhot, Francoi, Von Gunten, Stephan, Gyssens, Inge, Halter, Jörg, Harrison, Claire, Harteveld, Corneli, Hellström Lindberg, Eva, Hermine, Olivier, Higgs, Dougla, Hillmen, Peter, Hirsch, Han, Hoskin, Peter, Huls, Gerwin, Inati, Adlette, Johnson, Peter, Kattamis, Antoni, Kiefel, Volker, Kleanthous, Marina, Klump, Hanne, Krause, Daniela, Hovinga, Johanna Kremer, Lacaud, George, Lacroix Desmazes, Sébastien, Landman Parker, Judith, Legouill, Steven, Lenz, Georg, Von Lilienfeld Toal, Marie, Von Lindern, Marieke, Lopez Guillermo, Armando, Lopriore, Enrico, Lozano, Miguel, Macintyre, Elizabeth, Makris, Michael, Mannhalter, Christine, Martens, Joost, Mathas, Stephan, Matzdorff, Axel, Medvinsky, Alexander, Menendez, Pablo, Migliaccio, Anna Rita, Miharada, Kenichi, Mikulska, Malgorzata, Minard, Véronique, Montalbán, Carlo, De Montalembert, Mariane, Montserrat, Emili, Morange, Pierre Emmanuel, Mountford, Joanne, Muckenthaler, Martina, Müller Tidow, Carsten, Mumford, Andrew, Nadel, Bertrand, Navarro, Jose Toma, El Nemer, Wassim, Noizat Pirenne, France, O’Mahony, Brian, Oldenburg, Johanne, Olsson, Martin, Oostendorp, Robert, Palumbo, Antonio, Passamonti, Francesco, Patient, Roger, De Latour, Regis Peffault, Pflumio, Francoise, Pierelli, Luca, Piga, Antonio, Pollard, Debra, Raaijmakers, Marc, Radford, John, Rambach, Ralf, Koneti Rao, A., Raslova, Hana, Rebulla, Paolo, Rees, David, Ribrag, Vincent, Rijneveld, Anita, Rinalducci, Sara, Robak, Tadeusz, Roberts, Irene, Rodrigues, Charlene, Rosendaal, Frit, Rosenwald, Andrea, Rule, Simon, Russo, Roberta, Saglio, Guiseppe, Sanchez, Mayka, Scharf, Rüdiger E., Schlenke, Peter, Semple, John, Sierra, Jorge, So Osman, Cynthia, Soria, José Manuel, Stamatopoulos, Kosta, Stegmayr, Bernd, Stunnenberg, Henk, Swinkels, Dorine, Barata, João Pedro Taborda, Taghon, Tom, Taher, Ali, Terpos, Evangelo, Thachil, Jecko, Tissot, Jean Daniel, Touw, Ivo, Toye, Ash, Trappe, Ralf, Traverse Glehen, Alexandra, Unal, Sule, Vaulont, Sophie, Viprakasit, Vip, Vitolo, Umberto, Van Wijk, Richard, Wójtowicz, Agnieszka, Zeerleder, Sacha, Zieger, Barbara, Hematology, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of York [York, UK], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pediatrics, Cell biology, Erasmus MC other, Pulmonary Medicine, Medical Oncology, Other departments, AII - Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention, ACS - Amsterdam Cardiovascular Sciences, Clinical Haematology, Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Döhner, H, De, Wit, Td, Eichinger, S, Fibbe, W, Green, T, de Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Salles, G, Schuringa, Jj, and the other authors of the EHA Roadmap for European Hematology, Research, Cancer Research UK, Biotechnology and Biological Sciences Research Council (BBSRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), De Wit, T, De Haas, F, Sall Es, G, Schuringa, J, André, M, Andre Schmutz, I, Bacigalupo, A, Bochud, P, Den Boer, M, Bonini, C, Camaschella, C, Cant, A, Cappellini, M, Cazzola, M, Celso, C, Dimopoulos, M, Douay, L, Dzierzak, E, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, De Haan, G, Hansen, J, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kühne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Méndez Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, S, Reitsma, P, Ribera, J, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard Mönch, K, Thein, S, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, A, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, J, Martinez, P, Van Den Akker, E, Allard, S, Anagnou, N, Andolfo, I, Andrau, J, Angelucci, E, Anstee, D, Aurer, I, Avet Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, Van Den Berg, A, Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Brækkan, S, Van Den Brink, M, Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Vives Corron, J, Da Costa, L, Davi, F, Delwel, R, Dianzani, I, Domanović, D, Donnelly, P, Drnovšek, T, Dreyling, M, Du, M, Dufour, C, Durand, C, Efremov, D, Eleftheriou, A, Elion, J, Emonts, M, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foà, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, Van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gökbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, Von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellström Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, J, Lacaud, G, Lacroix Desmazes, S, Landman Parker, J, Legouill, S, Lenz, G, Von Lilienfeld Toal, M, Von Lindern, M, Lopez Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Mannhalter, C, Martens, J, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, A, Miharada, K, Mikulska, M, Minard, V, Montalbán, C, De Montalembert, M, Montserrat, E, Morange, P, Mountford, J, Muckenthaler, M, Müller Tidow, C, Mumford, A, Nadel, B, Navarro, J, El Nemer, W, Noizat Pirenne, F, O’Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, De Latour, R, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Koneti Rao, A, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, A, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, R, Schlenke, P, Semple, J, Sierra, J, So Osman, C, Soria, J, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, J, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, J, Touw, I, Toye, A, Trappe, R, Traverse Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, Van Wijk, R, Wójtowicz, A, Zeerleder, S, Zieger, B, Andreas Engert, Carlo Balduini, Anneke Brand, Bertrand Coiffier, Catherine Cordonnier, Hartmut Döhner, Thom Duyvené de Wit, Sabine Eichinger, Willem Fibbe, Tony Green, Fleur de Haas, Achille Iolascon, Thierry Jaffredo, Francesco Rodeghiero, Gilles Salles, Jan Jacob Schuringa, the other authors of the EHA Roadmap for European Hematology Research, Anna Rita Migliaccio, EHA Roadmap for European Hematology, Research, Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Döhner, H., de Wit TD., Eichinger, S., Fibbe, W., Green, T., de Haas, F., Iolascon, A., Jaffredo, T., Rodeghiero, F., Salles, G., Schuringa, JJ., André, M., Andre-Schmutz, I., Bacigalupo, A., Bochud, PY., Boer, Md., Bonini, C., Camaschella, C., Cant, A., Cappellini, MD., Cazzola, M., Celso, CL., Dimopoulos, M., Douay, L., Dzierzak, E., Einsele, H., Ferreri, A., De Franceschi, L., Gaulard, P., Gottgens, B., Greinacher, A., Gresele, P., Gribben, J., de Haan, G., Hansen, JB., Hochhaus, A., Kadir, R., Kaveri, S., Kouskoff, V., Kühne, T., Kyrle, P., Ljungman, P., Maschmeyer, G., Méndez-Ferrer£££Simón£££ S., Milsom, M., Mummery, C., Ossenkoppele, G., Pecci, A., Peyvandi, F., Philipsen, S., Reitsma, P., Ribera, JM., Risitano, A., Rivella, S., Ruf, W., Schroeder, T., Scully, M., Socie, G., Staal, F., Stanworth, S., Stauder, R., Stilgenbauer, S., Tamary, H., Theilgaard-Mönch, K., Thein, SL., Tilly, H., Trneny, M., Vainchenker, W., Vannucchi, AM., Viscoli, C., Vrielink, H., Zaaijer, H., Zanella, A., Zolla, L., Zwaginga, JJ., Martinez, PA., van den Akker, E., Allard, S., Anagnou, N., Andolfo, I., Andrau, JC., Angelucci, E., Anstee, D., Aurer, I., Avet-Loiseau, H., Aydinok, Y., Bakchoul, T., Balduini, A., Barcellini, W., Baruch, D., Baruchel, A., Bayry, J., Bento, C., van den Berg, A., Bernardi, R., Bianchi, P., Bigas, A., Biondi, A., Bohonek, M., Bonnet, D., Borchmann, P., Borregaard, N., Brækkan, S., van den Brink, M., Brodin, E., Bullinger, L., Buske, C., Butzeck, B., Cammenga, J., Campo, E., Carbone, A., Cervantes, F., Cesaro, S., Charbord, P., Claas, F., Cohen, H., Conard, J., Coppo, P., Corrons, JL., Costa, Ld., Davi, F., Delwel, R., Dianzani, I., Domanović, D., Donnelly, P., Drnov?ek£££Tadeja Dovč£££ TD., Dreyling, M., Du, MQ., Dufour, C., Durand, C., Efremov, D., Eleftheriou, A., Elion, J., Emonts, M., Engelhardt, M., Ezine, S., Falkenburg, F., Favier, R., Federico, M., Fenaux, P., Fitzgibbon, J., Flygare, J., Foà, R., Forrester, L., Galacteros, F., Garagiola, I., Gardiner, C., Garraud, O., van Geet, C., Geiger, H., Geissler, J., Germing, U., Ghevaert, C., Girelli, D., Godeau, B., Gökbuget, N., Goldschmidt, H., Goodeve, A., Graf, T., Graziadei, G., Griesshammer, M., Gruel, Y., Guilhot, F., von Gunten, S., Gyssens, I., Halter, J., Harrison, C., Harteveld, C., Hellström-Lindberg, E., Hermine, O., Higgs, D., Hillmen, P., Hirsch, H., Hoskin, P., Huls, G., Inati, A., Johnson, P., Kattamis, A., Kiefel, V., Kleanthous, M., Klump, H., Krause, D., Hovinga, JK., Lacaud, G., Lacroix-Desmazes, S., Landman-Parker, J., LeGouill, S., Lenz, G., von Lilienfeld-Toal, M., von Lindern, M., Lopez-Guillermo, A., Lopriore, E., Lozano, M., MacIntyre, E., Makris, M., Mannhalter, C., Martens, J., Mathas, S., Matzdorff, A., Medvinsky, A., Menendez, P., Migliaccio, AR., Miharada, K., Mikulska, M., Minard, V., Montalbán, C., de Montalembert, M., Montserrat, E., Morange, PE., Mountford, J., Muckenthaler, M., Müller-Tidow, C., Mumford, A., Nadel, B., Navarro, JT., Nemer, We., Noizat-Pirenne, F., O'Mahony, B., Oldenburg, J., Olsson, M., Oostendorp, R., Palumbo, A., Passamonti, F., Patient, R., Peffault, R., Pflumio, F., Pierelli, L., Piga, A., Pollard, D., Raaijmakers, M., Radford, J., Rambach, R., Rao, AK., Raslova, H., Rebulla, P., Rees, D., Ribrag, V., Rijneveld, A., Rinalducci, S., Robak, T., Roberts, I., Rodrigues, C., Rosendaal, F., Rosenwald, A., Rule, S., Russo, R., Saglio, G., Sanchez, M., Scharf, RE., Schlenke, P., Semple, J., Sierra, J., So-Osman, C., Soria, JM., Stamatopoulos, K., Stegmayr, B., Stunnenberg, H., Swinkels, D., Barata£££João Pedro Taborda£££ JP., Taghon, T., Taher, A., Terpos, E., Thachil, J., Tissot, JD., Touw, I., Toye, A., Trappe, R., Traverse-Glehen, A., Unal, S., Vaulont, S., Viprakasit, V., Vitolo, U., van Wijk, R., Wójtowicz, A., Zeerleder, S., Zieger, B., Stem Cell Aging Leukemia and Lymphoma (SALL), and Çocuk Sağlığı ve Hastalıkları
Subjects: 0301 basic medicine, Cancer Research, diagnosis, Health Services for the Aged, ACUTE PROMYELOCYTIC LEUKEMIA, Medizin, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, EHA Roadmap for European Hematology Research, Antineoplastic Agent, 0302 clinical medicine, European Hematology Association Roadmap, Germany, PERIPHERAL T-CELL, Medicine and Health Sciences, Hematopoiesi, genetics, Molecular Targeted Therapy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, Hematology, Genome, Hematopoietic Stem Cell Transplantation, Anemia, Awareness, Supply & distribution, Combined Modality Therapy, 3. Good health, Europe, THROMBOPOIETIN-RECEPTOR AGONISTS, Blood Disorder, Italy, Austria, haematology, Medicine, France, Immunotherapy, Infection, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Human, medicine.medical_specialty, Thrombopoietin Receptor Agonists, Consensus, Patients, Immunology, Antineoplastic Agents, Blood Coagulation, Gene Expression Profiling, Genetic Therapy, Genome, Human, Hematologic Diseases, Hematopoiesis, Humans, Consensu, [SDV.CAN]Life Sciences [q-bio]/Cancer, ACUTE MYELOID-LEUKEMIA, 1102 Cardiovascular Medicine And Haematology, Genetic therapy, methods, 03 medical and health sciences, blood, Internal medicine, medicine, Hematologi, THROMBOTIC THROMBOCYTOPENIC PURPURA, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, ACUTE LYMPHOBLASTIC-LEUKEMIA, therapy, business.industry, CHRONIC LYMPHOCYTIC-LEUKEMIA, supply & distribution, STEM-CELL TRANSPLANTATION, economics, Hematologic Disease, Opinion Article, Transplantation, 030104 developmental biology, Family medicine, therapeutic use, drug effects, RANDOMIZED-CONTROLLED-TRIAL, HEMOLYTIC-UREMIC SYNDROME, pathology, business, chemical synthesis, 030215 immunology, Stem Cell Transplantation, transplantation
Abstract: WOS: 000379156300012, PubMed ID: 26819058, The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients., Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [BB/L023776/1, BB/I00050X/1, BB/K021168/1]; Cancer Research UKCancer Research UK [11831]; Medical Research CouncilMedical Research Council UK (MRC) [G1000801a]; Novo Nordisk FondenNovo Nordisk [NNF12OC1015986]; British Heart FoundationBritish Heart Foundation [FS/09/039/27788]; Cancer Research UKCancer Research UK [12765]; Medical Research CouncilMedical Research Council UK (MRC) [MR/L022982/1, MC_UU_12009/8, MC_U137981013, MC_PC_12009]
Published: 2016
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28. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013

Author: Timothy P. Hughes, Martin C. Müller, Michael W. Deininger, Philippe Rousselot, Richard A. Larson, Michele Baccarani, Richard E. Clark, Fabrizio Pane, Andreas Hochhaus, Richard T. Silver, Henrik Hjorth-Hansen, Giuseppe Saglio, Jiri Mayer, Giovanni Martinelli, Jeffrey H. Lipton, Charles A. Schiffer, Dietger Niederwieser, Jerald P. Radich, Jane F. Apperley, Susanne Saußele, Gianantonio Rosti, Bengt Simonsson, François Guilhot, Francisco Cervantes, Simona Soverini, John M. Goldman, François Xavier Mahon, Juan Luis Steegmann, Rüdiger Hehlmann, Dong-Wook Kim, Hagop M. Kantarjian, Jorge E. Cortes, Baccarani, M, Deininger, Mw, Rosti, G, Hochhaus, A, Soverini, S, Apperley, Jf, Cervantes, F, Clark, Re, Cortes, Je, Guilhot, F, Hjorth Hansen, H, Hughes, Tp, Kantarjian, Hm, Kim, Dw, Larson, Ra, Lipton, Jh, Mahon, Fx, Martinelli, G, Mayer, J, M?ller, Mc, Niederwieser, D, Pane, Fabrizio, Radich, Jp, Rousselot, P, Saglio, G, Sau?ele, S, Schiffer, C, Silver, R, Simonsson, B, Steegmann, Jl, Goldman, Jm, Hehlmann, R., Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saußele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R., University of Bologna, University of Utah, and Université de Poitiers
Subjects: polymerase chain reaction, Fusion Proteins, bcr-abl, Review Article, protein-tyrosine kinase inhibitor, Biochemistry, Piperazines, cytogenetics, chemistry.chemical_compound, European LeukemiaNet, 0302 clinical medicine, imatinib mesylate, hemic and lymphatic diseases, dasatinib, BCR-ABL, Randomized Controlled Trials as Topic, 0303 health sciences, withdrawing treatment, Ponatinib, leukemia, Myeloid leukemia, Hematology, Prognosis, 3. Good health, Europe, chronic, Dasatinib, Treatment Outcome, 030220 oncology & carcinogenesis, Benzamides, medicine.drug, medicine.medical_specialty, myelocytic, Immunology, Antineoplastic Agents, second line treatment, 03 medical and health sciences, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, TYROSINE KINASE INHIBITORS, Humans, nilotinib, 030304 developmental biology, allogeneic stem cell transplant, business.industry, Cell Biology, Discontinuation, Transplantation, Thiazoles, Pyrimidines, Imatinib mesylate, Nilotinib, chemistry, business, CHRONIC MYELOID LEUKEMIA (CML), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Stem Cell Transplantation, transplantation
Abstract: Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, 10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome–positive [Ph+] >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
Published: 2013
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29. Sustained deep molecular responses in patients switched to nilotinib due to persistent BCR-ABL1 on imatinib: final ENESTcmr randomized trial results

Author: Sandip Acharya, Timothy P. Hughes, Agnès Guerci-Bresler, Anthony P. Schwarer, Ricardo Pasquini, Tara Glynos, Nelson Spector, Jeffrey H. Lipton, Francisco Cervantes, Darshan Dalal, Pedro Enrique Dorlhiac-Llacer, Mahon Fx, Brian Leber, Delphine Rea, Nelma D Clementino, Susan Branford, Suzanne Kamel-Reid, Israel Bendit, Hughes, TP, Leber, B, Cervantes, F, Spector, N, Pasquini, R, Clementino, NCD, Schwarer, AP, Dorlhiac-Llacer, PE, Mahon, FX, Rea, D, Guerci-Bresler, A, Kamel-Reid, S, Bendit, I, Acharya, S, Glynos, T, Dalal, D, Lipton, JH, and Branford, S
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Fusion Proteins, bcr-abl, Antineoplastic Agents, Pharmacology, patients, law.invention, 03 medical and health sciences, Bcr abl1, 0302 clinical medicine, Randomized controlled trial, law, hemic and lymphatic diseases, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, molecular responses, Humans, In patient, Letter to the Editor, Protein Kinase Inhibitors, Cross-Over Studies, business.industry, Imatinib, Hematology, Crossover study, Clinical trial, Imatinib mesylate, Pyrimidines, Nilotinib, 030220 oncology & carcinogenesis, Imatinib Mesylate, business, 030215 immunology, medicine.drug
Abstract: Sustained deep molecular responses in patients switched to nilotinib due to persistent BCR-ABL1 on imatinib: final ENESTcmr randomized trial results
Published: 2017

30. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance

Author: Sarit Assouline, Dong-Wook Kim, Vikram Mathews, Jie Jin, Zhi Xiang Shen, Edo Vellenga, H. Jean Khoury, Ricardo Pasquini, Andrey Zaritskey, Hagop M. Kantarjian, Simon Durrant, Tim H. Brümmendorf, Jorge E. Cortes, Anna G. Turkina, Francisco Cervantes, Carlo Gambacorti-Passerini, Kathleen Turnbull, Eric Leip, Tamas Masszi, Virginia Kelly, Nadine Besson, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), GAMBACORTI PASSERINI, C, Brümmendorf, T, Kim, D, Turkina, A, Masszi, T, Assouline, S, Durrant, S, Kantarjian, H, Khoury, H, Zaritskey, A, Shen, Z, Jin, J, Vellenga, E, Pasquini, R, Mathews, V, Cervantes, F, Besson, N, Turnbull, K, Leip, E, Kelly, V, and Cortes, J
Subjects: Male, DIAGNOSED CHRONIC-PHASE, NILOTINIB, DURABLE CYTOGENETIC RESPONSES, Gastroenterology, Piperazines, hemic and lymphatic diseases, Aged, 80 and over, DASATINIB, Hematology, Aniline Compounds, CHRONIC MYELOGENOUS LEUKEMIA, Myeloid leukemia, Middle Aged, Dasatinib, Treatment Outcome, Benzamides, Leukemia, Myeloid, Chronic-Phase, Imatinib Mesylate, Quinolines, Female, TRIAL, Bosutinib, Complete Hematologic Response, medicine.drug, Adult, medicine.medical_specialty, Adolescent, ABL, INHIBITION, Antineoplastic Agents, chronic myeloid leukemia CML, Disease-Free Survival, Young Adult, Internal medicine, Nitriles, medicine, Humans, Protein Kinase Inhibitors, Aged, Dose-Response Relationship, Drug, business.industry, Imatinib, Original Articles, medicine.disease, THERAPY FAILURE, Surgery, Pyrimidines, Nilotinib, Drug Resistance, Neoplasm, SKI-606, business, Chronic myelogenous leukemia, Follow-Up Studies
Abstract: Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n = 200) or intolerant (n = 88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. http://ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00261846","term_id":"NCT00261846"}}NCT00261846. Am. J. Hematol. 89:732–742, 2014. © 2014 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.
Published: 2014

31. Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia

Author: Felipe Prosper, Juan A. Castillejo, Francisco Cervantes, Lucia Cordeu, Jose Roman-Gomez, German Navarro, Leire Garate, Anabel Heiniger, Xabier Agirre, Antonio Jiménez-Velasco, Edurne San José-Enériz, Antoni Torres, [Román-Gómez,J, Castillejo,JA, Torres,A] Hematology Department, Reina Sofia Hospital, Cordoba, Spain. [Jiménez-Velasco,A, Navarro,G, Heiniger,A] Hematology Department, Carlos Haya Hospital, Malaga, Spain. [Aguirre,X, San Jose-Eneriz,E, Garete,L, Cordeu,L, Prosper,F] Hematology Department, Cellular Therapy Area, Clinica Universitaria /School of Medicine, Foundation for Applied Medical Research. University of Navarra, Pamplona, Spain. [Cervantes,F] Hematology Department, Hospital Clinic, IDIBAPS, University of Barcelona, Spain., Supported by grants from Fondo de Investigacion Sanitaria (FIS, Spain) 06/0003, 03/0141, 01/0013-01, 01/F018, 02/1299, Navarra Goverment (31/2002), RETIC C03/10, Junta de Andalucia 03/143, and 03/144 and funds from IMABIS (Malaga. Spain), 'UTEproject CIMA',Fundación de Investigación Médica Mutua Madrileña Automovilista, and Asociacion Medicina e Investigacion (AMI).
Subjects: Male, Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Interferons [Medical Subject Headings], Hypomethylation, Piperazines, Regiones promotoras genéticas, Epigenesis, Genetic, DEAD-box RNA Helicases, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], HAGE, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation [Medical Subject Headings], hemic and lymphatic diseases, Testis, Promoter Regions, Genetic, CML, Regulation of gene expression, Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Leukemia, Myelogenous, Chronic, BCR-ABL Positive [Medical Subject Headings], Reverse Transcriptase Polymerase Chain Reaction, musculoskeletal, neural, and ocular physiology, Myeloid leukemia, Hematology, Methylation, Prognosis, Neoplasm Proteins, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction [Medical Subject Headings], Gene Expression Regulation, Neoplastic, Leukemia, Benzamides, DNA methylation, Imatinib Mesylate, Cancer/testis antigens, psychological phenomena and processes, Metilación del ADN, Cancer testis antigens, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Antineoplastic Agents, Biology, Antigens, Neoplasm, Cell Line, Tumor, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::CpG Islands [Medical Subject Headings], medicine, Humans, Retractions, cardiovascular diseases, Leucemia mielogenosa crónica BCR-ABL positiva, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::RNA Nucleotidyltransferases::RNA Helicases::DEAD-box RNA Helicases [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines [Medical Subject Headings], DNA Methylation, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Neoplasm [Medical Subject Headings], medicine.disease, Pirimidinas, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings], Interferones, Pyrimidines, Imatinib mesylate, Immunology, Cancer research, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Regulatory Elements, Transcriptional::Promoter Regions, Genetic [Medical Subject Headings], CpG Islands, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Piperazines [Medical Subject Headings], Interferons, Anatomy::Urogenital System::Genitalia::Genitalia, Male::Testis [Medical Subject Headings], K562 cells
Abstract: Journal Article; BACKGROUND AND OBJECTIVES Cancer testis antigens (CTA) provide attractive targets for cancer-specific immunotherapy. Although CTA genes are expressed in some normal tissues, such as the testis, this immunologically protected site lacks MHC I expression and as such, does not present self antigens to T cells. To date, CTA genes have been shown to be expressed in a range of solid tumors via demethylation of their promoter CpG islands, but rarely in chronic myeloid leukemia (CML) or other hematologic malignancies. DESIGN AND METHODS In this study, the methylation status of the HAGE CTA gene promoter was analyzed by quantitative methylation-specific polymerase chain reaction (MSP) and sequencing in four Philadelphia-positive cell lines (TCC-S, K562, KU812 and KYO-1) and in CML samples taken from patients in chronic phase (CP n=215) or blast crisis (BC n=47). HAGE expression was assessed by quantitative reverse transcriptase-polymerase chain reaction. RESULTS The TCC-S cell line showed demethylation of HAGE that was associated with over-expression of this gene. HAGE hypomethylation was significantly more frequent in BC (46%) than in CP (22%) (p=0.01) and was correlated with high expression levels of HAGE transcripts (p
Published: 2007
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32. Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia

Author: François Guilhot, Laurie Letvak, Richard A. Larson, Bayard L. Powell, Hermine Agis, Norbert Gattermann, Francisco Cervantes, Andreas Hochhaus, Brian J. Druker, Richard T. Silver, Hagop M. Kantarjian, Charlene So, Bengt Simonsson, Thea Kolsen Fischer, Jerald P. Radich, John D. Shepherd, Johan Lanng Nielsen, Alois Gratwohl, Jan J. Cornelissen, Insa Gathmann, Stephen G. O'Brien, Janice Gabrilove, Josy Reiffers, Michael W. Deininger, Kerry Taylor, Richard Stone, Michele Baccarani, Philippe Rousselot, Gregor Verhoef, John M. Goldman, Giuseppe Saglio, Timothy P. Hughes, Medical Oncology, Hematology, Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, and Larson RA
Subjects: Male, Oncology, medicine.medical_specialty, Fusion Proteins, bcr-abl, Antineoplastic Agents, Kaplan-Meier Estimate, Chronic phase chronic myelogenous leukemia, Disease-Free Survival, Piperazines, chemistry.chemical_compound, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Omacetaxine mepesuccinate, medicine, Humans, neoplasms, business.industry, Ponatinib, Cytarabine, Interferon-alpha, Myeloid leukemia, Imatinib, General Medicine, Protein-Tyrosine Kinases, Survival Analysis, Survival Rate, Dasatinib, Pyrimidines, Treatment Outcome, Imatinib mesylate, chemistry, Nilotinib, Benzamides, Immunology, Imatinib Mesylate, Female, business, Follow-Up Studies, medicine.drug
Abstract: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy.We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events.The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events.After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
Published: 2006
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33. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts

Author: Pierre Laneuville, Vishnu Reddy, Nelson Spector, Nelson Hamerschlak, Eduardo Olavarria, Richard A. Van Etten, Richard E. Clark, Dina Ben Yehuda, Jorge Milone, Ziad Salem, Richard T. Silver, Beatriz Moiraghi, Israel Bendit, David Gómez-Almaguer, Kensuke Usuki, Carmino DeSouza, Raquel Bengió, Madan Jagasia, Anthony P. Schwarer, Ayalew Tefferi, Tetsuzo Tauchi, Güray Saydam, Massimo Breccia, Pankaj Malhotra, Andrew Grigg, Jerald P. Radich, Camille N. Abboud, Moshe Talpaz, Elisabetta Abruzzese, Jenny Byrne, Guillermo J. Ruiz-Argüelles, Daniel J. DeAngelo, Francois-Xavier Mahon, Michael W. Deininger, Philipp le Coutre, Carlos Best, Ryuzo Ohno, Giuseppe Saglio, Jane F. Apperley, José A. López, Eduardo Bullorsky, Christopher Arthur, Richard Stone, Carolina Pavlovsky, Ibrahim C. Haznedaroglu, Ellin Berman, Alfonso Quintás-Cardama, David Marin-Costa, Johan Richter, Jianxiang Wang, Eduardo Cervera, Neil P. Shah, Saengsuree Jootar, Meir Wetzler, Jianda Hu, Richard A. Larson, Alvaro Aguayo, Timothy P. Hughes, Philippe Rousselot, Dragana Milojkovic, Xiao-Jun Huang, Iryna Dyagil, Steven M. Devine, Peter Browett, Vernon J. Louw, Kimmo Porkka, Hossam Kamel, Jesper Stentoft, Qian Jiang, Manuel Ayala, Andrey Zaritskey, Naeem Chaudhri, Muheez A. Durosinmi, John M. Goldman, Anna G. Turkina, Susan O'Brien, Jiri Mayer, Alicia Magarinos, Fawzi Abdel-Rahman, Brian J. P. Huntly, Hugues de Lavallade, Constantine S. Tam, Francisco Cervantes, Tessa L. Holyoake, Amir T. Fathi, Carlo Gambacorti-Passerini, Ekaterina Chelysheva, Adam D. Cohen, Junia V. Melo, Ernesto Fanilla, Tariq I. Mughal, Elias Jabbour, Naoto Takahashi, Itaru Matsumura, Jean Khoury, Paul J. Shami, Charles A. Schiffer, Dong-Wook Kim, Luis Meillon, Bassam Francis Matti, Henrik Hjorth-Hansen, Mahmoud Aljurf, Ali Bazarbachi, Hemant Malhotra, Hagop M. Kantarjian, Giovanni Martinelli, Joseph O. Moore, Jorge E. Cortes, Arnon Nagler, Paolo Vigneri, Ricardo Pasquini, Javier Pinilla-Ibarz, Elza Lomaia, Brian J. Druker, Tapan Saikia, David S. Snyder, Kazunori Ohnishi, Jeffrey H. Lipton, Pia Raanani, Abboud, C, Berman, E, Cohen, A, Cortes, J, Deangelo, D, Deininger, M, Devine, S, Druker, B, Fathi, A, Jabbour, E, Jagasia, M, Kantarjian, H, Khoury, J, Laneuville, P, Larson, R, Lipton, J, Moore, J, Mughal, T, O'Brien, S, Pinilla-Ibarz, J, Quintas-Cardama, A, Radich, J, Reddy, V, Schiffer, C, Shah, N, Shami, P, Silver, R, Snyder, D, Stone, R, Talpaz, M, Tefferi, A, Van Etten, R, Wetzler, M, Abruzzese, E, Apperley, J, Breccia, M, Byrne, J, Cervantes, F, Chelysheva, E, Clark, R, De Lavallade, H, Dyagil, I, Gambacorti-Passerini, C, Goldman, J, Haznedaroglu, I, Hjorth-Hansen, H, Holyoake, T, Huntly, B, Le Coutre, P, Lomaia, E, Mahon, F, Marin-Costa, D, Martinelli, G, Mayer, J, Milojkovic, D, Olavarria, E, Porkka, K, Richter, J, Rousselot, P, Saglio, G, Saydam, G, Stentoft, J, Turkina, A, Vigneri, P, Zaritskey, A, Aguayo, A, Ayala, M, Bendit, I, Bengio, R, Best, C, Bullorsky, E, Cervera, E, Desouza, C, Fanilla, E, Gomez-Almaguer, D, Hamerschlak, N, Lopez, J, Magarinos, A, Meillon, L, Milone, J, Moiraghi, B, Pasquini, R, Pavlovsky, C, Ruiz-Arguelles, G, Spector, N, Arthur, C, Browett, P, Grigg, A, Jianda, H, Huang, X, Hughes, T, Jiang, Q, Jootar, S, Kim, D, Malhotra, H, Malhotra, P, Matsumura, I, Melo, J, Ohnishi, K, Ohno, R, Saikia, T, Schwarer, A, Takahashi, N, Tam, C, Tauchi, T, Usuki, K, Wang, J, Abdel-Rahman, F, Aljurf, M, Bazarba-Chi, A, Yehuda, D, Chaudhri, N, Durosinmi, M, Kamel, H, Louw, V, Matti, B, Nagler, A, Raanani, P, and Salem, Z
Subjects: medicine.medical_specialty, Drug Industry, Cost effectiveness, Cancer drugs, Immunology, Alternative medicine, Antineoplastic Agents, Pharmacology, Biochemistry, Drug Costs, Antineoplastic Agent, Patents as Topic, Myelogenous, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Health care, Medicine, Drugs, Generic, Humans, Intensive care medicine, health care economics and organizations, Drug Cost, business.industry, Myeloid leukemia, Hematology, Cell Biology, medicine.disease, Leukemia, business, Large group, Human
Abstract: As a group of more than 100 experts in chronic myeloid leukemia (CML), we draw attention to the high prices of cancer drugs, with the particular focus on the prices of approved tyrosine kinase inhibitors for the treatment of CML. This editorial addresses the multiple factors involved in cancer drug pricing and their impact on individual patients and health care policies, and argues for the need to (1) lower the prices of cancer drugs to allow more patients to afford them and (2) maintain sound long-term health care policies.
Published: 2013

34. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet

Author: Rüdiger Hehlmann, Michael W. Deininger, Alois Gratwohl, Frederick R. Appelbaum, Michele Baccarani, François Guilhot, Hagop M. Kantarjian, Jorge E. Cortes, Dietger Niederwieser, Andreas Hochhaus, Mary M. Horowitz, Richard T. Silver, Francisco Cervantes, Bengt Simonsson, John M. Goldman, Giuseppe Saglio, Richard A. Larson, Timothy P. Hughes, Jane F. Apperley, Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, Apperley J, Cervantes F, Cortes J, Deininger M, Gratwohl A, Guilhot F, Horowitz M, Hughes T, Kantarjian H, Larson R, Niederwieser D, Silver R, and Hehlmann R
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Immunology, Antineoplastic Agents, Hematopoietic stem cell transplantation, Transplantation, Autologous, Biochemistry, Chronic phase chronic myelogenous leukemia, Piperazines, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Transplantation, Homologous, Philadelphia Chromosome, Treatment Failure, Intensive care medicine, Chromosome Aberrations, business.industry, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Cell Biology, Hematology, Prognosis, medicine.disease, Combined Modality Therapy, Recombinant Proteins, Hematologic Response, Transplantation, Leukemia, Pyrimidines, Imatinib mesylate, Drug Resistance, Neoplasm, Benzamides, Interferon Type I, Mutation, Imatinib Mesylate, business, Complete Hematologic Response
Abstract: The introduction of imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML). Although experience is too limited to permit evidence-based evaluation of survival, the available data fully justify critical reassessment of CML management. The panel therefore reviewed treatment of CML since 1998. It confirmed the value of IM (400 mg/day) and of conventional allogeneic hematopoietic stem cell transplantation (alloHSCT). It recommended that the preferred initial treatment for most patients newly diagnosed in chronic phase should now be 400 mg IM daily. A dose increase of IM, alloHSCT, or investigational treatments were recommended in case of failure, and could be considered in case of suboptimal response. Failure was defined at 3 months (no hematologic response [HR]), 6 months (incomplete HR or no cytogenetic response [CgR]), 12 months (less than partial CgR [Philadelphia chromosome-positive (Ph(+)) > 35%]), 18 months (less than complete CgR), and in case of HR or CgR loss, or appearance of highly IM-resistant BCR-ABL mutations. Suboptimal response was defined at 3 months (incomplete HR), 6 months (less than partial CgR), 12 months (less than complete CgR), 18 months (less than major molecular response [MMolR]), and, in case of MMolR loss, other mutations or other chromosomal abnormalities. The importance of regular monitoring at experienced centers was highlighted.
Published: 2006

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34 results on '"Cervantes F."'

1. Genomic characterization of patients with polycythemia vera developing resistance to hydroxyurea.

2. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia.

3. Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms.

4. Sustained deep molecular responses in patients switched to nilotinib due to persistent BCR-ABL1 on imatinib: final ENESTcmr randomized trial results.

5. No influence of BCR-ABL1 transcript types e13a2 and e14a2 on long-term survival: results in 1494 patients with chronic myeloid leukemia treated with imatinib.

6. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia.

7. Imatinib dose reduction in patients with chronic myeloid leukemia in sustained deep molecular response.

8. Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease.

9. Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial.

10. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily.

11. Cytoreduction plus low-dose aspirin versus cytoreduction alone as primary prophylaxis of thrombosis in patients with high-risk essential thrombocythaemia: an observational study.

12. Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia.

13. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet.

14. Epigenetic down-regulation of BIM expression is associated with reduced optimal responses to imatinib treatment in chronic myeloid leukaemia.

15. [Chronic myeloid leukemia 2008].

16. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia.

17. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.

18. Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia.

19. Cadherin-13, a mediator of calcium-dependent cell-cell adhesion, is silenced by methylation in chronic myeloid leukemia and correlates with pretreatment risk profile and cytogenetic response to interferon alfa.

20. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.

21. Imatinib mesylate (STI571) treatment in patients with chronic-phase chronic myelogenous leukaemia previously submitted to autologous stem cell transplantation.

22. Imatinib mesylate (Gleevec, Glivec): a new therapy for chronic myeloid leukemia and other malignancies.

23. Progressive multifocal leukoencephalopathy following oral fludarabine treatment of chronic lymphocytic leukemia.

24. Chronic systemic candidiasis in acute leukemia.

25. Fludarabine for prolymphocytic leukaemia and risk of interstitial pneumonitis.

26. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

27. The European Hematology Association Roadmap for European Hematology Research: a consensus document

28. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013

29. Sustained deep molecular responses in patients switched to nilotinib due to persistent BCR-ABL1 on imatinib: final ENESTcmr randomized trial results

30. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance

31. Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia

32. Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia

33. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts

34. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet

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34 results on '"Cervantes F."'

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