18 results on '"Simonsson B"'
Search Results
2. Dasatinib (SPRYCEL®) in Patients (pts) with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Who Are Imatinib-Resistant (im-r) or -Intolerant (im-i): Updated Results from the CA180-015 ‘START-L’ Study.
- Author
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Dombret, Herve, primary, Ottmann, O.G., additional, Rosti, G., additional, Simonsson, B., additional, Larson, R.A., additional, Gollerkeri, A., additional, Apanovitch, A., additional, Radich, J., additional, and Coutre, Steven, additional
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- 2006
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- View/download PDF
3. A Phase II Study of Dasatinib in Patients with Chronic Myeloid Leukemia (CML) in Lymphoid Blast Crisis or Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Who Are Resistant or Intolerant to Imatinib: The ‘START-L’ CA180015 Study.
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Ottmann, Oliver G., primary, Martinelli, G., primary, Dombret, H., primary, Kantarjian, H., primary, Hochhaus, A., primary, Simonsson, B., primary, Aloe, A., primary, Apanovitch, A., primary, and Shah, N., primary
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- 2005
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4. Serum levels of soluble intercellular adhesion molecule 1 are increased in chronic B-lymphocytic leukemia and correlate with clinical stage and prognostic markers [see comments]
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Christiansen, I, primary, Gidlof, C, additional, Wallgren, AC, additional, Simonsson, B, additional, and Totterman, TH, additional
- Published
- 1994
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5. T-cell activation and subset patterns are altered in B-CLL and correlate with the stage of the disease
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Totterman, TH, Carlsson, M, Simonsson, B, Bengtsson, M, and Nilsson, K
- Abstract
Two-color FACS analysis was used to study activated and “functional” T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T- suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T- cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.
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- 1989
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6. B-cell reconstitution after autologous bone marrow transplantation: increase in serum CD23 ("IgE-binding factor") precedes IgE and B-cell regeneration
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Bengtsson, M, Gordon, J, Flores-Romo, L, Cairns, JA, Smedmyr, B, Oberg, G, Simonsson, B, and Totterman, TH
- Abstract
The serum levels of IgE and the soluble cleavage product of CD23 (sCD23) were prospectively monitored for up to 1 year after transplantation in 34 patients who underwent autologous (n = 33) or syngeneic (n = 1) bone marrow transplantation (BMT). In 25 patients (74%), a transient IgE peak (two- to 2,750-fold increase) appeared in the serum 3 to 4 weeks after BMT. In 18 patients (51%), a two- to 125- fold increase in sCD23 coincided with the IgE peak. In only three patients was a sCD23 peak observed without a concomitant increase in IgE. The sCD23 increment preceded the IgE peak in each individual case. During the period of increased sCD23 serum levels, the absolute numbers of circulating B cells and other cell types expressing surface CD23 were extremely low. The biologic significance of these findings is discussed in light of present knowledge of regulation of B-cell growth and differentiation with special reference to the role of sCD23 as a multifunctional cytokine.
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- 1989
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7. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study
- Author
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Ashwin Gollerkeri, Jerald P. Radich, Oliver G. Ottmann, Richard A. Larson, Steven Coutre, A. Apanovitch, Giovanni Martinelli, Bengt Simonsson, Hervé Dombret, Andreas Hochhaus, Giovanna Rege-Cambrin, François Guilhot, Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, Rege-Cambrin G, Radich J, Hochhaus A, Apanovitch AM, Gollerkeri A, and Coutre S.
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Time Factors ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,medicine.drug_class ,Immunology ,Fusion Proteins, bcr-abl ,Phases of clinical research ,Biochemistry ,Piperazines ,Tyrosine-kinase inhibitor ,Cytogenetics ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,DASATINIB ,Hematology ,business.industry ,Imatinib ,Drug Tolerance ,Cell Biology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA ,Dasatinib ,Thiazoles ,CYTOGENETIC RESPONSES ,Pyrimidines ,Imatinib mesylate ,Tolerability ,Drug Resistance, Neoplasm ,Benzamides ,Mutation ,Imatinib Mesylate ,Female ,business ,Febrile neutropenia ,Follow-Up Studies ,medicine.drug - Abstract
Patients with Philadelphia (Ph) chromosome–positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015.
- Published
- 2007
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8. Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry.
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Höglund M, Sandin F, Hellström K, Björeman M, Björkholm M, Brune M, Dreimane A, Ekblom M, Lehmann S, Ljungman P, Malm C, Markevärn B, Myhr-Eriksson K, Ohm L, Olsson-Strömberg U, Själander A, Wadenvik H, Simonsson B, Stenke L, and Richter J
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Male, Middle Aged, Prognosis, Sex Factors, Survival Rate, Sweden epidemiology, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Protein Kinase Inhibitors therapeutic use, Protein-Tyrosine Kinases antagonists & inhibitors, Registries statistics & numerical data
- Abstract
Clinical management guidelines on malignant disorders are generally based on data from clinical trials with selected patient cohorts. In Sweden, more than 95% of all patients diagnosed with chronic myeloid leukemia (CML) are reported to the national CML registry, providing unique possibilities to compile population-based information. This report is based on registry data from 2002 to 2010, when a total of 779 patients (425 men, 354 women; median age, 60 years) were diagnosed with CML (93% chronic, 5% accelerated, and 2% blastic phase) corresponding to an annual incidence of 0.9/100,000. In 2002, approximately half of the patients received a tyrosine kinase inhibitor as initial therapy, a proportion that increased to 94% for younger (<70 years) and 79% for older (>80 years) patients during 2007-2009. With a median follow-up of 61 months, the relative survival at 5 years was close to 1.0 for patients younger than 60 years and 0.9 for those aged 60 to 80 years, but only 0.6 for those older than 80 years. At 12 months, 3% had progressed to accelerated or blastic phase. Sokal, but not European Treatment and Outcome Study, high-risk scores were significantly linked to inferior overall and relative survival. Patients living in university vs nonuniversity catchment areas more often received tyrosine kinase inhibitors up front but showed comparable survival.
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- 2013
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9. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013.
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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, and Hehlmann R
- Subjects
- Antineoplastic Agents therapeutic use, Benzamides therapeutic use, Dasatinib, Europe, Fusion Proteins, bcr-abl metabolism, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines therapeutic use, Prognosis, Pyrimidines therapeutic use, Randomized Controlled Trials as Topic, Stem Cell Transplantation, Thiazoles therapeutic use, Treatment Outcome, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- 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, <1% at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas >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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10. Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet.
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Guilhot J, Baccarani M, Clark RE, Cervantes F, Guilhot F, Hochhaus A, Kulikov S, Mayer J, Petzer AL, Rosti G, Rousselot P, Saglio G, Saussele S, Simonsson B, Steegmann JL, Zaritskey A, and Hehlmann R
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- Community Networks organization & administration, Disease-Free Survival, Endpoint Determination methods, Endpoint Determination statistics & numerical data, Europe, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Models, Biological, Practice Guidelines as Topic, Protein Kinase Inhibitors therapeutic use, Quality of Life, Research Design, Survival Analysis, Time Factors, Treatment Outcome, Clinical Trials, Phase III as Topic methods, Clinical Trials, Phase III as Topic statistics & numerical data, Data Interpretation, Statistical, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
The treatment policy of chronic myeloid leukemia (CML), particularly with tyrosine kinase inhibitors, has been influenced by several recent studies that were well designed and rapidly performed, but their interpretation is of some concern because different end points and methodologies were used. To understand and compare the results of the previous and future studies and to translate their conclusion into clinical practice, there is a need for common definitions and methods for analyses of CML studies. A panel of experts was appointed by the European LeukemiaNet with the aim of developing a set of definitions and recommendations to be used in design, analyses, and reporting of phase 3 clinical trials in this disease. This paper summarizes the consensus of the panel on events and major end points of interest in CML. It also focuses on specific issues concerning the intention-to-treat principle and longitudinal data analyses in the context of long-term follow-up. The panel proposes that future clinical trials follow these recommendations.
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- 2012
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11. The EUTOS CML score aims to support clinical decision-making.
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Hoffmann V, Baccarani M, Hasford J, Guilhot J, Saussele S, Rosti G, Guilhot F, Porkka K, Ossenkoppele G, Lindoerfer D, Simonsson B, Pfirrmann M, and Hehlmann R
- Subjects
- Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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- 2012
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12. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia.
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Simonsson B, Gedde-Dahl T, Markevärn B, Remes K, Stentoft J, Almqvist A, Björeman M, Flogegård M, Koskenvesa P, Lindblom A, Malm C, Mustjoki S, Myhr-Eriksson K, Ohm L, Räsänen A, Sinisalo M, Själander A, Strömberg U, Bjerrum OW, Ehrencrona H, Gruber F, Kairisto V, Olsson K, Sandin F, Nagler A, Nielsen JL, Hjorth-Hansen H, and Porkka K
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Benzamides, Biomarkers analysis, Drug Dosage Calculations, Female, Fusion Proteins, bcr-abl analysis, Fusion Proteins, bcr-abl biosynthesis, Humans, Imatinib Mesylate, Interferon-alpha administration & dosage, Interferon-alpha adverse effects, Male, Middle Aged, Piperazines administration & dosage, Piperazines adverse effects, Polyethylene Glycols administration & dosage, Polyethylene Glycols adverse effects, Polymerase Chain Reaction, Protein-Tyrosine Kinases analysis, Protein-Tyrosine Kinases biosynthesis, Pyrimidines administration & dosage, Pyrimidines adverse effects, Recombinant Proteins administration & dosage, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Risk Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Piperazines therapeutic use, Polyethylene Glycols therapeutic use, Pyrimidines therapeutic use, Remission Induction methods
- Abstract
Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg-IFN-α2b) 50 μg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
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- 2011
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13. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score.
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Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, Guilhot F, Porkka K, Ossenkoppele G, Lindoerfer D, Simonsson B, Pfirrmann M, and Hehlmann R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Basophils pathology, Benzamides, Disease Progression, Disease-Free Survival, Female, Humans, Imatinib Mesylate, Male, Middle Aged, Predictive Value of Tests, Prognosis, Registries statistics & numerical data, Risk Assessment methods, Risk Factors, Spleen pathology, Young Adult, Antineoplastic Agents administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Models, Statistical, Piperazines administration & dosage, Pyrimidines administration & dosage
- Abstract
The outcome of chronic myeloid leukemia (CML) has been profoundly changed by the introduction of tyrosine kinase inhibitors into therapy, but the prognosis of patients with CML is still evaluated using prognostic scores developed in the chemotherapy and interferon era. The present work describes a new prognostic score that is superior to the Sokal and Euro scores both in its prognostic ability and in its simplicity. The predictive power of the score was developed and tested on a group of patients selected from a registry of 2060 patients enrolled in studies of first-line treatment with imatinib-based regimes. The EUTOS score using the percentage of basophils and spleen size best discriminated between high-risk and low-risk groups of patients, with a positive predictive value of not reaching a CCgR of 34%. Five-year progression-free survival was significantly better in the low- than in the high-risk group (90% vs 82%, P = .006). These results were confirmed in the validation sample. The score can be used to identify CML patients with significantly lower probabilities of responding to therapy and survival, thus alerting physicians to those patients who require closer observation and early intervention.
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- 2011
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14. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study.
- Author
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Baccarani M, Rosti G, Castagnetti F, Haznedaroglu I, Porkka K, Abruzzese E, Alimena G, Ehrencrona H, Hjorth-Hansen H, Kairisto V, Levato L, Martinelli G, Nagler A, Lanng Nielsen J, Ozbek U, Palandri F, Palmieri F, Pane F, Rege-Cambrin G, Russo D, Specchia G, Testoni N, Weiss-Bjerrum O, Saglio G, and Simonsson B
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Benzamides, Cytogenetic Analysis, Dose-Response Relationship, Drug, Europe, Female, Fusion Proteins, bcr-abl genetics, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Prognosis, Protein-Tyrosine Kinases antagonists & inhibitors, Risk Factors, Survival Rate, Treatment Outcome, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines administration & dosage, Protein Kinase Inhibitors administration & dosage, Pyrimidines administration & dosage
- Abstract
Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic use of a higher dose of IM could lead to better results, 216 patients with Ph(+) CML at high risk (HR) according to the Sokal index were randomly assigned to receive IM 800 mg or 400 mg daily, as front-line therapy, for at least 1 year. The CCgR rate at 1 year was 64% and 58% for the high-dose arm and for the standard-dose arm, respectively (P = .435). No differences were detectable in the CgR at 3 and 6 months, in the molecular response rate at any time, as well as in the rate of other events. Twenty-four (94%) of 25 patients who could tolerate the full 800-mg dose achieved a CCgR, and only 4 (23%) of 17 patients who could tolerate less than 350 mg achieved a CCgR. This study does not support the extensive use of high-dose IM (800 mg daily) front-line in all CML HR patients. This trial was registered at www.clinicaltrials.gov as #NCT00514488.
- Published
- 2009
- Full Text
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15. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study.
- Author
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Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, Rege-Cambrin G, Radich J, Hochhaus A, Apanovitch AM, Gollerkeri A, and Coutre S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Benzamides, Cytogenetics, Dasatinib, Drug-Related Side Effects and Adverse Reactions, Female, Follow-Up Studies, Fusion Proteins, bcr-abl genetics, Hematology, Humans, Imatinib Mesylate, Male, Middle Aged, Mutation genetics, Piperazines pharmacology, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Pyrimidines adverse effects, Pyrimidines pharmacology, Thiazoles adverse effects, Thiazoles pharmacology, Time Factors, Chromosome Aberrations drug effects, Drug Resistance, Neoplasm, Drug Tolerance, Piperazines therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Pyrimidines therapeutic use, Thiazoles therapeutic use
- Abstract
Patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015.
- Published
- 2007
- Full Text
- View/download PDF
16. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet.
- Author
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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
- Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Benzamides, Chromosome Aberrations, Combined Modality Therapy, Drug Resistance, Neoplasm genetics, Hematopoietic Stem Cell Transplantation, Humans, Imatinib Mesylate, Interferon Type I therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Mutation, Philadelphia Chromosome, Piperazines administration & dosage, Piperazines therapeutic use, Prognosis, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Recombinant Proteins, Transplantation, Autologous, Transplantation, Homologous, Treatment Failure, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- 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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17. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.
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Brune M, Castaigne S, Catalano J, Gehlsen K, Ho AD, Hofmann WK, Hogge DE, Nilsson B, Or R, Romero AI, Rowe JM, Simonsson B, Spearing R, Stadtmauer EA, Szer J, Wallhult E, and Hellstrand K
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Histamine adverse effects, Humans, Interleukin-2 adverse effects, Male, Middle Aged, Proportional Hazards Models, Recurrence, Remission Induction, Survival Rate, Treatment Outcome, Histamine therapeutic use, Immunotherapy, Interleukin-2 therapeutic use, Leukemia, Myeloid therapy
- Abstract
The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.
- Published
- 2006
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18. Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders.
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Bonifazi F, de Vivo A, Rosti G, Guilhot F, Guilhot J, Trabacchi E, Hehlmann R, Hochhaus A, Shepherd PC, Steegmann JL, Kluin-Nelemans HC, Thaler J, Simonsson B, Louwagie A, Reiffers J, Mahon FX, Montefusco E, Alimena G, Hasford J, Richards S, Saglio G, Testoni N, Martinelli G, Tura S, and Baccarani M
- Subjects
- Adult, Aged, Antineoplastic Agents administration & dosage, Biomarkers, Tumor blood, Bone Marrow Transplantation, Cause of Death, Combined Modality Therapy, Europe epidemiology, Female, Follow-Up Studies, Fusion Proteins, bcr-abl blood, Humans, Immunologic Factors administration & dosage, Interferon alpha-2, Interferon-alpha administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Life Tables, Male, Middle Aged, Recombinant Proteins, Remission Induction, Retrospective Studies, Risk Factors, Survival Analysis, Treatment Outcome, Antineoplastic Agents therapeutic use, Immunologic Factors therapeutic use, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-alpha), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-alpha alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-alpha treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients.
- Published
- 2001
- Full Text
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