28 results match your criteria nilotinib cessation

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Dose Optimization of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A New Therapeutic Challenge.

J Clin Med 2021 Feb 1;10(3). Epub 2021 Feb 1.

Hematology, Department of Translational and Precision Medicine, Sapienza University, Policlinico Umberto 1, 00161 Rome, Italy.

The chronic myeloid leukemia (CML) therapeutic landscape has dramatically changed with tyrosine kinase inhibitor (TKI) development, which allows a near-normal life expectancy. However, long-term TKI exposure has been associated with persistent adverse events (AEs) which negatively impact on quality of life (QoL) and have the potential to cause significant morbidity and mortality. In clinical practice, TKI dose reduction is usually considered to reduce AEs and improve QoL, but dose optimization could have also another aim, i. Read More

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February 2021

[Management of vascular adverse events during tyrosine kinase inhibitors in patients with chronic myeloid leukemia].

Authors:
Tomoiku Takaku

Rinsho Ketsueki 2020 ;61(9):1018-1027

Department of Hematology, Juntendo University Graduate School of Medicine.

In 2000, imatinib became the first tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myeloid leukemia (CML); this was soon followed by second generation (nilotinib, dasatinib, and bosutinib) and third generation (ponatinib) TKIs, all of which are currently available for the treatment of CML. Their emergence has revolutionized treatment strategies for CML, leading to a new era that has seen the 10-year overall survival rate for CML patients exceed 80%; despite the impact of TKIs on CML prognosis, only 10 to 20% of CML patients maintain treatment-free remission after TKI cessation. Moreover, prolonged treatment produces various adverse effects, such as serious vascular adverse events including stroke, myocardial infarction, and peripheral arterial occlusive disease. Read More

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January 2021

Dasatinib associated lymphadenopathy in a chronic myeloid leukemia patient: A case report.

Medicine (Baltimore) 2020 Nov;99(45):e22791

First Propedeutic Department of Internal Medicine, AHEPA University Hospital, Medical School.

Rationale: Dasatinib associated lymphadenopathy (DAL) is a rare adverse event in chronic myeloid leukemia patients (CML). A case of voluminous lymphadenopathy in the context of DAL is presented.

Patient Concerns: A 40-year-old male patient was diagnosed with BCR-ABL1 positive chronic stage CML 2 years ago and achieved complete molecular response on nilotinib, which was switched to dasatinib due to nilotinib intolerance. Read More

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November 2020

Successful Treatment of End-stage Renal Disease in a Patient With Chronic Myeloid Leukemia by Kidney Transplantation and Tyrosine Kinase Inhibitors: A Case Report.

Transplant Proc 2020 Mar 3;52(2):604-607. Epub 2020 Feb 3.

Department of Urology, Keio University School of Medicine, Tokyo, Japan.

Consensus regarding kidney transplantation feasibility in patients with chronic myeloid leukemia (CML) well controlled by tyrosine kinase inhibitors has not yet been achieved. Here, we report a patient with CML well controlled by tyrosine kinase inhibitors who developed end-stage renal disease during treatment and underwent kidney transplantation. CML activity has been carefully and successfully controlled for 4 years post-transplant. Read More

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Nilotinib-Induced Dystonia and Cognitive Deficits in a Neurologically Normal Patient with Chronic Myeloid Leukemia.

Case Rep Neurol Med 2019 12;2019:3679319. Epub 2019 Nov 12.

Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.

Nilotinib is a tyrosine kinase inhibitor used to treat patients with chronic myeloid leukemia (CML). This agent is also being studied in neurodegenerative disorders including Parkinson disease. Studies have shown that nilotinib may decrease the accumulation of parkin substrates and decrease the loss of dopaminergic cells. Read More

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November 2019

Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years: a multicenter phase 2 trial, stop nilotinib (NILSt).

Int J Hematol 2019 Dec 19;110(6):675-682. Epub 2019 Sep 19.

Department of Hematology and Oncology, Osaka University, Osaka, Japan.

The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300-400 mg twice daily for up to 24 months. Patients who maintained MR at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. Read More

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December 2019

The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia.

Blood Adv 2019 04;3(7):1084-1091

Department of Clinical Haematology, Austin Hospital, Melbourne, Australia.

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Read More

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Chronic Myeloid Leukemia Patient's Voice About the Experience of Treatment-Free Remission Failure: Results From the Italian Sub-Study of ENESTPath Exploring the Emotional Experience of Patients During Different Phases of a Clinical Trial.

Front Psychol 2019 20;10:329. Epub 2019 Feb 20.

Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy.

The main objective of this study is to gain further insights on how chronic myeloid leukemia (CML) patients involved in an interventional clinical trial with the purpose of reaching treatment free remission (TFR) phase, perceived and experienced TFR failure. TFR failure was defined for the individual patient as either not being eligible for drug discontinuation or as having relapse in the TFR phase with reintroduction of nilotinib treatment. Using a qualitative approach, out of 25 patients with CML who experienced TFR failure 14 were interviewed. Read More

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February 2019

The effect of tyrosine kinase inhibitor interruption and interferon use on pregnancy outcomes and long-term disease control in chronic myeloid leukemia.

Leuk Lymphoma 2019 07 11;60(7):1796-1802. Epub 2019 Jan 11.

a Department of Clinical Hematology , Austin Hospital , Heidelberg , Australia.

The management of CML in pregnancy is challenging with the need to balance disease control against potential teratogenic effects of TKI therapy. In this multi-center case-cohort study of 16 women in chronic phase, CML ceased TKI treatment pre- or post-conception during their first pregnancy. Thirteen patients were on imatinib; 9 ceased their TKI prior to conception and 7 ceased at pregnancy confirmation. Read More

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Chronic myeloid leukemia stem cells and molecular target therapies for overcoming resistance and disease persistence.

Int J Hematol 2018 Oct 28;108(4):365-370. Epub 2018 Aug 28.

Department of Hematology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.

Chronic myeloid leukemia (CML) is effectively treated with tyrosine kinase inhibitors (TKI) targeted against BCR-ABL. We previously reported the investigation of residual CML diseases during TKI treatment using FACS-sorting and quantitative RT-PCR of BCR-ABL among each population; total mononuclear cells, hematopoietic stem cells, and myeloid progenitors. The observations also implied that the second-generation of ABL-tyrosine kinase inhibitors (2nd TKIs), dasatinib or nilotinib therapy can be more promising approach for efficient reduction of the CML stem cells. Read More

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October 2018

Long-lasting memory of cellular immunity in a chronic myeloid leukemia patient maintains molecular response 5 after cessation of dasatinib.

Oncol Lett 2018 Mar 29;15(3):2935-2938. Epub 2017 Dec 29.

Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki 852-8511, Japan.

Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Read More

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A unique and promising combination of medications for the treatment of Alzheimer's disease.

Med Hypotheses 2017 Nov 24;109:53-55. Epub 2017 Sep 24.

Marshall University School of Medicine, 1600 Medical Center Dr, Huntington, WV 25701, United States. Electronic address:

At present there is no therapy for Alzheimer's Disease which completely stops the progressive dementia effecting late onset Alzheimer's Disease (AD) patients. It is felt that the main reason for this failure is that AD appears to be a disease caused by four major pathological processes. To date, efforts to develop treatments have addressed only one or another of these four etiologies. Read More

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November 2017

Spontaneous intramural small bowel hematoma in a patient with acute myeloid leukaemia receiving chemotherapy and nilotinib.

BMJ Case Rep 2017 Sep 27;2017. Epub 2017 Sep 27.

Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Spontaneous intramural small bowel hematoma (SISBH) is a rare, acute abdominal condition, with increasing incidence in recent years. Excessive anticoagulation with vitamin K antagonists is the most common aetiology. We report the case of a large acute jejunal intramural hematoma in a patient with newly diagnosed acute myeloid leukaemia receiving chemotherapy and nilotinib. Read More

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September 2017

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies.

Clin Lymphoma Myeloma Leuk 2017 Dec 14;17(12):834-851. Epub 2017 Jul 14.

Department of Dermatology, Stanford University School of Medicine, Stanford, CA. Electronic address:

The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies. Read More

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December 2017

De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial.

Lancet Haematol 2017 Jul 26;4(7):e310-e316. Epub 2017 May 26.

Paul O'Gorman Leukaemia Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Background: Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia with deep molecular responses; however, patients with stable major molecular response (MMR), but not MR4, have not been studied, nor has the effect of treatment de-escalation rather than outright cessation. We aimed to examine the effects of treatment de-escalation as a prelude to complete cessation, not only in patients with MR4 or greater, but also in those with MMR but not MR4.

Methods: We did this interim analysis of a non-randomised, phase 2 trial at 20 hospitals in the UK. Read More

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The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.

Nature 2017 03 22;543(7647):733-737. Epub 2017 Mar 22.

Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA.

Chronic myeloid leukaemia (CML) is driven by the activity of the BCR-ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Read More

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Cardiovascular Complications of Targeted Therapies for Chronic Myeloid Leukemia.

Curr Treat Options Cardiovasc Med 2017 Apr;19(4):24

Cardio-Oncology Program, Division of Cardiovascular Medicine, University of South Florida and H. Lee Moffitt Cancer Center & Research Institute, 2 Tampa General Circle, Tampa, FL, 33606, USA.

Opinion Statement: The development of tyrosine kinase inhibitors (TKIs) dramatically changed the treatment landscape for many different cancers including chronic myeloid leukemia (CML). With the introduction of imatinib, the first TKI developed and approved to effectively treat CML, patient survival has increased dramatically and, in some cases, this fatal cancer can be managed as a chronic disease. Since the approval of imatinib in 2002, four additional TKIs have been developed to treat this disease including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib. Read More

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CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors.

Blood 2017 03 3;129(9):1166-1176. Epub 2017 Jan 3.

Department of Haematology, SA Pathology, Adelaide, SA, Australia.

Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment-free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n = 21), on TKI (imatinib, nilotinib, dasatinib) before achieving major molecular response (pre-MMR, >0.1%, n = 8), MMR ( ≤0. Read More

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Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.

Leukemia 2017 05 28;31(5):1108-1116. Epub 2016 Nov 28.

Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden.

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. Read More

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Pneumatosis intestinalis during chemotherapy with nilotinib in a patient with chronic myeloid leukemia who tested positive for anti-topoisomerase I antibodies.

Clin J Gastroenterol 2016 Dec 16;9(6):358-364. Epub 2016 Sep 16.

Department of Medical Oncology, Sapporo Medical University, Sapporo, Japan.

A 55-year-old man with several comorbidities including idiopathic interstitial pneumonia under long-term corticosteroid therapy, longstanding myocardial infarction, chronic heart failure, paroxysmal atrial fibrillation, gastro-esophageal reflux disease, constipation, and history of paralytic ileus, was diagnosed with chronic myelogenous leukemia (CML) in the chronic phase. He also tested positive for anti-topoisomerase I antibodies without clinical diagnosis of any connective tissue disease, including systemic sclerosis. Approximately 5 months after the initiation of nilotinib for CML, he developed upper abdominal distension with intermitting abdominal pain, and based on abdominal computed tomography findings, a diagnosis of pneumatosis intestinalis (PI) was made. Read More

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December 2016

First line treatment with newer tyrosine kinase inhibitors in chronic myeloid leukemia associated with deep and durable molecular response - systematic review and meta-analysis.

Acta Oncol 2016 Sep - Oct;55(9-10):1077-1083. Epub 2016 Aug 25.

a Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.

Background: The choice of a specific tyrosine kinase inhibitor (TKI) as first line treatment in chronic myeloid leukemia (CML) is complex and influenced by multiple factors. We published a meta-analysis examining the role of newer TKIs as first line treatment in chronic phase CML. In view of the recently published data, we decided to update it. Read More

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January 2018

Gastric Antral Vascular Ectasia during the Treatment of Chronic Myelogenous Leukemia with Imatinib Mesylate.

Intern Med 2016 ;55(1):69-72

Division of Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Japan.

This report describes three patients with chronic myelogenous leukemia who developed gastric antral vascular ectasia (GAVE) during treatment with imatinib mesylate (IM). Cessation and/or switching from IM to nilotinib resulted in the alleviation of gastrointestinal (GI) bleeding and ectatic lesions. Furthermore, GI bleeding recurred after the re-administration of IM in one patient. Read More

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Nilotinib and peginterferon alfa-2a for newly diagnosed chronic-phase chronic myeloid leukaemia (NiloPeg): a multicentre, non-randomised, open-label phase 2 study.

Lancet Haematol 2015 Jan 7;2(1):e37-46. Epub 2015 Jan 7.

Laboratory of Haematology, Hôpital Haut Lévêque, avenue de Magellan, 33604 Pessac, France; French group of CML (Fi-LMC group), Laboratory of Haematology, Hôpital Haut Lévêque, Pessac, France.

Background: Nilotinib is now recommended for patients with newly diagnosed chronic myeloid leukaemia in chronic phase and leads to important rates of molecular response 4·5 log (MR(4·5)), allowing the prospect of therapy cessation. However, most patients do not reach this criterion and nilotinib is taken for lengthy periods, resulting in chronic or late-onset adverse events. Nilotinib combined with interferon might further increase rates of MR(4·5), avoid late side-effects, and allow therapy cessation. Read More

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January 2015

Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

Anticancer Res 2013 Aug;33(8):3509-14

Hematology Unit, First Department of Internal Medicine, Laiko Hospital, University of Athens, 17 Agiou Thoma Street, Athens 11527, Greece.

Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Read More

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[Successive cutaneous adverse reactions to nilotinib and imatinib in a single patient].

Ann Dermatol Venereol 2012 Dec 31;139(12):828-31. Epub 2012 Oct 31.

Service d'hématologie et d'oncologie pédiatrique, hôpital 20-Août-1953, CHU Ibn Rochd, 1, quartier des hôpitaux, Casablanca, Maroc.

Background: Since the advent of targeted molecules, the treatment and prognosis of many cancers, especially chronic myeloid leukemia (CML), have been substantially modified through the introduction of first- and second-generation tyrosine kinase inhibitors. Skin effects constitute the most common adverse effects of these new substances. Although such skin changes are not life-threatening, they can have extensive clinical impact, in some cases leading to discontinuation of treatment. Read More

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December 2012

Effects of BCR-ABL inhibitors on anti-tumor immunity.

Authors:
M Krusch H R Salih

Curr Med Chem 2011 ;18(34):5174-84

Department of Hematology and Oncology, Eberhard Karls University, Otfried-Mueller Str. 10, 72076 Tuebingen, Germany.

In chronic myeloid leukemia (CML), BCR-ABL-mediated oncogenic signaling can be successfully targeted with the BCRABL- inhibitors imatinib, nilotinib, and dasatinib leading to complete cytogenetic (Philadelphia chromosome not detectable upon cytogenetic testing of bone marrow) and even complete molecular (BCR-ABL not detectable by PCR in peripheral blood) responses. However, CML apparently can not be cured by BCR-ABL inhibitors alone, likely due to treatment-resistance of CML stem/progenitor cells, which provokes a relapse of disease after cessation of therapy. Evidence from patients treated with allogenic stem cell transplantation or IFN-α points to an important role of anti-tumor immunity for durable control of CML disease. Read More

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Dynamics of mutant BCR-ABL-positive clones after cessation of tyrosine kinase inhibitor therapy.

Haematologica 2011 Mar 6;96(3):360-6. Epub 2010 Dec 6.

III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.

Background: Point mutations of the BCR-ABL tyrosine kinase domain are considered the predominant cause of imatinib resistance in chronic myeloid leukemia. The expansion of mutant BCR-ABL-positive clones under selective pressure of tyrosine kinase inhibition is referred to as clonal selection; there are few data on the reversibility of this phenomenon.

Design And Methods: The changes of expression of mutant BCR-ABL-positive alleles after cessation of tyrosine kinase inhibitor treatment were examined in 19 patients with chronic myeloid leukemia harboring different mutations in a longitudinal follow-up. Read More

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Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter?

Blood 2009 Dec 30;114(27):5426-35. Epub 2009 Oct 30.

Centre for Cancer Biology, Departments of Molecular Pathology and Haematology, SA Pathology, Adelaide, Australia.

Preclinical studies of BCR-ABL mutation sensitivity to nilotinib or dasatinib suggested that the majority would be sensitive. Correspondingly, the initial clinical trials demonstrated similar response rates for CML patients after imatinib failure, irrespective of the mutation status. However, on closer examination, clinical evidence now indicates that some mutations are less sensitive to nilotinib (Y253H, E255K/V, and F359V/C) or dasatinib (F317L and V299L). Read More

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December 2009
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