China
Africa
Explore chapters and articles related to this topic
Bayesian Cure Model
Published in Yingwei Peng, Binbing Yu, Cure Models, 2021
We restricted the analysis to the patients with CML and considered the event as relapse or treatment-related mortality. Therefore, the cured patients are those who did not have either event. The Kaplan-Meier survival curves for the 3 donor groups are shown in Figure 7.3. The survival curves clearly reach a plateau in 60 months after bone marrow transplant. The patients with HLA-identically matched donors have the highest long-term survival rates.
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Another use of these technological advances is to develop “personalized” therapeutic agents tailored to these genetic differences (or biomarkers). A good example of this is the kinase inhibitor imatinib (GleevecTM) used to treat a type of leukemia known as Chronic Myeloid Leukemia (CML). It was initially discovered that CML is caused by a translocation mutation in which parts of two different chromosomes fuse together, leading to a uniquely mutated kinase protein (BCR-ABL) which is only found in the tumor cells of these patients and not their healthy cells. This created an opportunity (exploited by the pharmaceutical company Novartis) to discover a drug that could fit into the ATP-binding pocket of the BCR-ABL protein thus providing a very effective and highly selective treatment (see Chapter 6). Therefore, a pharmacogenomic assay is carried out on leukemia patients to confirm that they have the BCR-ABL mutation before imatinib is prescribed. Based on this, there is a growing trend for clinicians to order a predictive pre-prescription genetic test to identify potential responders (or nonresponders), or those who are likely to suffer adverse drug reactions (ADRs), before treatment is initiated. Table 11.1 shows a few examples of genes associated with different cancer types.
Targeting BCR-ABL in Chronic Myelogenous Leukemia
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, accounts for about 15% of all adult leukemia. In 2020, an estimate of 8450 individuals are expected to be diagnosed with new cases of CML and 1130 death will occur in the United States [1]. The BCR-ABL fusion gene (Philadelphia chromosome, Ph) encodes the BCR-ABL hybrid protein, and plays a central role in the pathogenesis of CML. It is present in more than 95% of CML cases. In general, progress of CML is classified into three phases: an asymptomatic chronic phase (CP), intermediate accelerated phase (AP) and the terminal blast phase (BP).
The efficacy and safety of eltrombopag in treating TKI-induced thrombocytopenia in patients with chronic myeloid leukemia
Published in Hematology, 2023
Li Liu, Yilin Chen, Yan Liang, Li Meng, Jingming Guo, Chuancai Liu, Zhe Zhao, Jing Zou, Wenjuan He, Jiangzhao Zhang, Zhenya Hong, Caixia Liang, Xianjie Fu, Hui Wu, Youshan Zhang, Yanli Zhang, Weiming Li
Chronic myelogenous leukemia (CML) is a blood cancer with specific chromosomal abnormalities. The widespread availability of tyrosine kinase inhibitors (TKI) allows most patients to achieve a normal life expectancy. Currently, five TKIs have been approved for treatment by the FDA: imatinib, nilotinib, dasatinib, bosutinib, and ponatinib [1]. Although TKI is well tolerated, there are still numerous adverse reactions. Among these, hematologic adverse reactions, especially ≥ grade 3 cytopenia, are the primary indicators for TKI reduction and discontinuation [2]. However, frequent dose reduction and interruption may reduce the efficacy of TKI [3]. Thrombocytopenia is one of the most common hematological adverse reactions in CML patients receiving TKI therapy, causing life-threatening bleeding cases. Reports of first-line TKI treatment revealed that the incidence of ≥ grade 3 thrombocytopenia was 4% to 14% with imatinib 400 mg/d, and it was 10% to 14% on nilotinib 600 mg/d, and 14% to 22% when dasatinib was used at 100 mg/d [4–7].
Dual inhibition of STAT3 and STAT5 may overcome imatinib resistance in chronic myeloid leukemia
Published in Hematology, 2023
Lingling Yin, Jiawen Xu, Wenjian Wu, Mingshan Niu, Zhenyu Li, Feng Zhu, Kailin Xu
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR::ABL1 fusion gene, which results from the Philadelphia chromosome, accounting for approximately 15% of all newly diagnosed cases of leukemia in adults. Clinical outcome of patients with CML has improved dramatically since the introduction of tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM), which are now considered standard therapy for CML patients [1]. Despite this success, several clinical challenges still exist. Approximately 20–30% of the patients eventually experience IM resistance. In addition, TKIs do not completely eradicate the leukemic stem cells [2]. Therefore, new therapeutic strategies to cure CML are important and challenging tasks.
Measuring prognosis in chronic myeloid leukemia: what’s new?
Published in Expert Review of Hematology, 2021
Massimo Breccia, Fabio Efficace, Emilia Scalzulli, Giulia Ciotti, Giacomo Maestrini, Gioia Colafigli, Maurizio Martelli
For example, an analysis conducted on CP-CML patients treated with nilotinib provide some preliminary evidence of the possible predictive value of PRO data. Using a well-validated PRO measure of fatigue, in univariate analysis it was found that patients with greater physical fatigue severity at baseline were less likely to achieve an MMR. Further multivariable analysis controlling for age, sex, hemoglobin level, spleen size, platelet count, blast cells, performance status, comorbidity, previous treatment, and dose reduction/interruption, confirming the independent predictive value of patient’s self-reported fatigue severity with a OR of 0.960 (p = 0.005) for achievement of MMR. This OR = 0.960 indicated a 40% decrease in the odds to achieve MMR at any time point, every 10-points increase (i.e. worsening) in the baseline fatigue scale used in this study [95]. Major research efforts are needed in this area to explore the potential prognostic value of PRO data in patients with CML.