1,721,207 research outputs found
A review of the European LeukemiaNet recommendations for the management of CML
No full textSeveral guidelines and recommendations on the management of chronic myeloid leukemia (CML) have been prepared by several scientific societies. The European LeukemiaNet (ELN) appointed a panel of experts who submitted their recommendations to peer-reviewed scientific journals in 2006, 2009, and 2013. Here, we make a critical review of the last, 2013, ELN recommendations, concerning the use of the five available tyrosine kinase inhibitors (TKIs), the evaluation of cytogenetic and molecular response, and the strategy of treatment. Three TKIs (imatinib, nilotinib, dasatinib) are recommended first-line. Bosutinib and ponatinib are available second-line; ponatinib is particularly indicated in case of the T315I mutation. Achieving an optimal response, not only for survival but also for a deeper, stable, treatment-free remission, requires a BCR-ABL transcripts level ≤ 10 % at 3 months, ≤ 1 % at 6 months, ≤ 0.1 % at 1 year, and ≤ 0.01 % later on. Molecular monitoring must include mutational analysis in every case of failure. A successful treatment of accelerated and blastic phase requires TKIs, and in many cases also allogeneic stem cell transplantation
Dosing Strategies for Improving the Risk-Benefit Profile of Ponatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase
No full textThe treatment of chronic myeloid leukemia (CML) has been advanced by the
development of small-molecule tyrosine kinase inhibitors (TKIs), which
target the fusion protein BCR-ABL1 expressed by the Philadelphia
chromosome. Ponatinib is a 3rd generation TKI that binds BCR-ABL1 with
high affinity and inhibits most BCR-ABL1 mutants, including the T315I
mutation. The approved starting dose of ponatinib is 45 mg once daily
(full dose), however, the need for a full dose, especially in patients
with dose adjustments due to tolerability problems, remains
undemonstrated. Lower starting doses of ponatinib (30 mg or 15 mg once
daily) for patients ``with lesser degrees of resistance or multiple
intolerances, especially those with an increased cardiovascular risk
profile{''} has been recommended by the 2020 European LeukemiaNet.
However, the available literature and guidance on the use of ponatinib
at low dosage are limited. The objective of this paper is to describe
how we select ponatinib dosage for CML patients in chronic phase in our
clinical practice based on the available evidence and our clinical
experience. We propose dosing regimens for the optimal starting dose for
six generic cases of CML patients in chronic phase eligible for the
switch to ponatinib and provide an algorithm to guide ponatinib dosing
during treatment
Safety profiles of first-line TKIS and managing adverse effects
No full textThe treatment armamentarium of chronic myeloid leukemia (CML) is based on at least five TKIs, employed either in first-line CP (imatinib, dasatinib, and nilotinib) and in second and third line (dasatinib, nilotinib, bosutinib, and ponatinib). These drugs share the same target of interest (BCR-ABL) but have profound different off-target effects. In turn, the general spectrum of adverse events experienced by the treated patients, either clinical symptoms, biochemical abnormalities, or severe AEs (or âcomplicationsâ), varies considerably. SAEs are more frequent with second- and third-generation TKIs, and from this point of view, imatinib remains the safest drug. The early identification of CML patient candidates to experience more frequently SAEs with second (and third)-generation TKIs is of course part of the treatment decision process where the right balance between risk and benefit should be accomplished. Second-generation TKIs, nilotinib and dasatinib, are considered generally to be better tolerated than imatinib. However, two types of complications are described more frequently with nilotinib and ponatinib (cardiovascular, in general, and PAOD in particular) and with dasatinib (pleural effusions and pulmonary hypertension) if compared with imatinib. These two types of complications deserve a particular attention
Tyrosine kinase inhibitors in chronic myeloid leukaemia: Which, when, for whom?
No full textThe therapeutic armamentarium for chronic myeloid leukaemia (CML) comprises mainly tyrosine kinase inhibitors (TKIs), with several agents available for frontline treatment, or for the treatment of disease resistance or intolerance to the first-choice or second-choice drug. The availability of different drugs is a major achievement, but means that choices must be made-which can be difficult and questionable at times. The most important end point considered in decision-making regarding treatment for any cancer is overall survival, but additional factors (such as age, prognostic category, safety, or the possibility of achieving treatment-free remission) should be considered when selecting an agent for frontline treatment. Regardless of the TKI selected for first-line treatment, guidelines that define the importance of reaching specific response indicators and procedures for vigilant follow-up monitoring are established to ensure timely implementation of second-line TKIs. Herein, we discuss the benefits and risks of the different TKIs available for the treatment of patients with CML, and how to decide when to employ these agents at different treatment settings
A review and an update of European leukemianet recommendations for the management of chronic myeloid leukemia
No full textThe European LeukemiaNet (ELN) is a network of excellence articulated in several working packages (WP) dedicated to research in haematologic malignancies. The ELN WP 4 that is dedicated to chronic myeloid leukaemia (CML) begun in 2004 to discuss the management of CML in the era of tyrosine kinase inhibitors (TKIs), in collaboration with several non-European experts. The discussion led to the elaboration of treatment recommendations that were published in 2006 (Baccarani et al. 2006). A second and a third revised versions were published in 2009 and 2013 (Baccarani et al. 2009a, 2013). These recommendations were received favourably by the scientific community, the health-care professionals, and the patients, have provided shared definitions and a common language, and in several countries have contributed to a rationale and successful management of the disease. A fourth version is in preparation. In this chapter, we do not provide a formal, comprehensive, and detailed review of the recommendations that can be better found in the original publications. Here, we discuss in more details some issues that are critical and have undergone changes since 2012, when the last version was submitted. The members of the ELN CML panel have not been involved in the preparation of this chapter. All the opinions and the suggestions that are included in this chapter reflect the opinions and the personal experience of the authors. It is not intended to modify the original ELN recommendations, but to contribute to an open discussion on some critical issues, particularly on the definition of the phases of CML, on the characteristics of old and new risk scores, and on the prognostic value of several biologic risk factors. We also discuss the response to treatment, with focus on molecular response, the first-line treatment with focus on the choice between imatinib and second-generation TKIs, and on the goals of treatment. The value of second- and third-line treatment is highlighted. The issues of treatment discontinuation for treatment-free remission (TFR) and of chronic treatment continuation in patients who cannot achieve TFR, and of BCR-ABL1+ stem cells, are discussed and reviewed
TREATMENT RECOMMENDATIONS FOR CHRONIC MYELOID LEUKEMIA
Full text linkThe first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy. At the end of the last century, about 15 years ago, all these treatments were quickly replaced by a class of small molecules targeting the tyrosine kinases (TK), which were able to induce a major molecular remission in most of the patients, without remarkable side effects, and a very prolonged life-span. The first approved TK inhibitor (TKI) was Imatinib Mesylate (Glivec or Gleevec, Novartis). Rapidly, other TKIs were developed tested and commercialized, namely Dasatinib (Sprycel, Bristol-Myers Squibb), Nilotinib (Tasigna, Novartis), Bosutinib (Busulif, Pfizer) and Ponatinib (Iclusig, Ariad). Not all these compounds are available worldwide; some of them are approved only for second line treatment, and the high prices are a problem that can limit their use. A frequent update of treatment recommendations is necessary. The current treatment goals include not only the prevention of the transformation to the advanced phases and the prolongation of survival, but also a length of survival and of a quality of life comparable to that of non-leukemic individuals. In some patient the next ambitious step is to move towards a treatment-free remission. The CML therapy, the role of alloSCT and the promising experimental strategies are reviewed in the context of the new therapeutic goals
A Review of the Therapeutic Role of Bosutinib in Chronic Myeloid Leukemia
Full text link: The development of the BCR::ABL1 tyrosine kinase inhibitors (TKIs) has transformed Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) from a fatal disease to an often-indolent illness that, when managed effectively, can restore a life expectancy close to that of the normal population. Bosutinib is a second-generation TKI approved for adults with Ph-positive CML in chronic phase, accelerated phase, or blast phase that is resistant or intolerant to prior therapy, and for newly diagnosed Ph-positive chronic phase CML. This review details the efficacy of bosutinib for the treatment of CML in the first- and second-line settings, as well as in third- and later-line settings for high-risk patients resistant or intolerant to at least 2 TKIs. It also outlines bosutinib studies that provide evidence for dose-optimization strategies that can be used to improve efficacy and effectively manage adverse events. The studies that provide evidence for specific patient populations benefiting particularly from bosutinib dose-optimization strategies are also discussed. The well-established, long-term side-effect profile and the potential to make dose adjustments with bosutinib make it an appropriate treatment option for patients with CML. Bosutinib has demonstrated a positive impact on health-related quality of life and an important role in the long-term treatment of patients with CML
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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