We studied by questionnaire 530 subjects with chronic myeloid leukaemia (CML) in Hubei Province during the recent SARS-CoV-2 epidemic. Five developed confirmed (N = 4) or probable COVID-19 (N = 1). Prevalence of COVID-19 in our subjects, 0.9% (95% Confidence Interval, 0.1, 1.8%) was ninefold higher than 0.1% (0, 0.12%) reported in normals but lower than 10% (6, 17%) reported in hospitalised persons with other haematological cancers or normal health-care providers, 7% (4, 12%). Co-variates associated with an increased risk of developing COVID-19 amongst persons with CML were exposure to someone infected with SARS-CoV-2 (P = 0.037), no complete haematologic response (P = 0.003) and co-morbidity(ies) (P = 0.024). There was also an increased risk of developing COVID-19 in subjects in advanced phase CML (P = 0.004) even when they achieved a complete cytogenetic response or major molecular response at the time of exposure to SARS-CoV-2. 1 of 21 subjects receiving 3rd generation tyrosine kinase-inhibitor (TKI) developed COVID-19 versus 3 of 346 subjects receiving imatinib versus 0 of 162 subjects receiving 2nd generation TKIs (P = 0.096). Other co-variates such as age and TKI-therapy duration were not significantly associated with an increased risk of developing COVID-19. Persons with these risk factors may benefit from increased surveillance of SARS-CoV-2 infection and possible protective isolation.
Dasatinib, a second-generation tyrosine kinase inhibitor, is recommended as first-line treatment for patients newly diagnosed with chronic myeloid leukemia (CML) and second-line treatment for those who are resistant or intolerant to therapy with imatinib. Dasatinib is superior to imatinib in terms of clinical response; however, the potential pulmonary toxicities associated with dasatinib, such as pulmonary arterial hypertension and pleural effusion, may limit its clinical use. Appropriate management of dasatinib-related severe events is important for improving the quality of life and prognosis of patients with CML. This review summarizes current knowledge regarding the characteristics, potential mechanisms, and clinical management of adverse reactions occurring after treatment of CML with dasatinib.
The therapeutic landscape for chronic myeloid leukemia (CML) has improved significantly with the approval of tyrosine kinase inhibitors (TKIs) for therapeutic use. Most patients with optimal responses to TKIs can have a normal life expectancy. Treatment-free remission (TFR) after discontinuing TKI has increasingly become a new goal for CML treatment. However, TKI only “control“ CML, and relapse after discontinuation has become a key factor hindering patient access to attempt TFR. In this study, we reviewed studies on TKI discontinuation, including both first and second-generation TKI. We also reviewed predictors of relapse, new monitoring methods, and strategies targeting leukemic stem cells.
Background. The tumor microenvironment (TME) plays a significant role in the progression and prognosis of acute myeloid leukemia (AML). This study is aimed at exploring TME-associated biomarkers and identify their potential mechanism in the microenvironment of AML. Method. In this study, the stromal, immune, and ESTIMATE scores of AML patients were evaluated with the ESTIMATE and CIBERSORT algorithms; then, the AML samples were divided into high- and low-score groups. We evaluated the association between clinicopathological characteristics, survival rate, and the stromal/immune/ESTIMATE scores. Furthermore, we identified TME-associated differentially expressed genes (DEGs) then carried out pathway enrichment analysis, protein-protein interaction (PPI) network, Cox regression analysis, and Kaplan-Meier survival analysis to select the most crucial genes. In addition, we further explored the potential mechanism of HCK in the AML microenvironment. Results. We identified 624 TME-associated DEGs and found that HCK was the most promising biomarker associated with AML. The results of the gene set enrichment analysis (GSEA) indicated that HCK was mainly involved in immune and inflammation-related signaling pathways. In addition, CIBERSORT analysis showed that HCK was closely related to tumor immune infiltration, with HCK expression associated with various infiltrating immune cells, including B cells, T cells, tumor-associated macrophages (TAM), NK cells, plasma cells, eosinophils, and neutrophils. Furthermore, HCK expression was closely related with ELN risk stratification in patients with AML. Conclusion. HCK could regulate immune cell infiltration in the microenvironment of AML and may act as a potential biomarker for the treatment and prognosis of AML patients.
Background: Imatinib is the first-line therapy recommended for chronic myeloid leukemia (CML) patients in China. We reported a long-term follow-up study of patients on imatinib as first-line treatment for chronic phase (CP) CML to provide an important reference for the actual clinical treatment regimen of CML patients in China.Methods: We evaluated the long-term efficacy, safety, low-dose attempt after years of treatment, and treatment-free remission (TFR) of 237 CML-CP patients receiving first-line imatinib therapy.Results: The median age was 46 years (interquartile range: 33–55). After a median follow-up of 6.5 years, the cumulative complete cytogenetic response, major molecular response (MMR), and MR4.5 rates were 82.6%, 80.4%, and 69.3%, respectively. The 10-year transformation-free, event-free, and failure-free survival rates were 97.3%, 87.2% and 53.5%, respectively. Fifty-two (21.9%) patients with sustained deep molecular response (DMR) were treated with low-dose imatinib after years of imatinib treatment. No significant differences in the 1-year and 2-year molecular relapse-free survival in MMR and MR4 were observed between the standard-dose and low-dose groups. Twenty-eight (11.8%) patients discontinued imatinib, and the median time to maintain DMR before discontinuation was 8.43 years. Thirteen patients (5.5%) remained in TFR for a median of 43.33 months. No patients transformed to accelerate or blast phase or died. No new, late toxicity was observed, and the most frequent grade 3/4 adverse events were neutropenia (9.3%), anemia (7.6%), thrombocytopenia (6.3%), and rash (4.2%).Conclusion: This study confirmed the long-term efficacy and safety of imatinib for treating Chinese CML patients. Additionally, it demonstrated the feasibility of imatinib dose reduction and TFR attempts in patients with sustained stable DMR after years of imatinib treatment in real-life settings.