Patients with von Willebrand disease in China: Results of an online survey.

INTRODUCTION: Little is known about the clinical characteristics of von Willebrand disease (VWD) patients in China, the impact of Covid-19 on them and their genetic mutation. AIM: To describe the clinical characteristics of a group of VWD patients in China, the impact of Covid-19 on them and their genetic mutation. METHODS: An online survey using a self-designed questionnaire was conducted among patients within a WeChat group of VWD patients in China. Data were analysed using t-test, the Chi-square test, Fisher's exact test and rank sum test. RESULTS: Data from a total of 96 patients were collected. Several important findings are yielded. Above all, type 3 patients accounted for over half of the surveyed patients. Secondly, a surprising rate (>40%) of patients had experience of being misdiagnosed. Thirdly, treatment regimens were dominated by cryoprecipitate, blood-derived FVIII and plasma, and only a small percentage of patients received prophylaxis. Fourthly, we identified 17 new von Willebrand factor (VWF) mutant genes which merit further investigation. Additionally, Covid-19 was found to pose some challenges for the patients. CONCLUSION: In China, the high rates of type 3 patients and misdiagnosis suggest that most of the VWD patients may never be diagnosed in China. When it comes to diagnosis and treatment, there is a large gap between developing countries like China and developed countries.

Clinical features and treatment effect of HIV-associated immune thrombocytopenia-single center Ten-Years data summary.

Thrombocytopenia represents one of the most prevalent hematologic complications observed in patients infected with the human immunodeficiency virus (HIV). In this study, we sought to analyze the clinical characteristics and treatment outcomes of patients with coexisting HIV and thrombocytopenia. Specifically, we retrospectively examined the medical records of 45 patients diagnosed with HIV/AIDS and thrombocytopenia at the Yunnan Infectious Diseases Specialist Hospital between January 2010 and December 2020, all of whom received highly active antiretroviral therapy (HAART) with/without glucocorticoids. The median follow-up period was 79 days, ranging between 14 and 368 days, the total platelet count was higher after receiving treatment than before (Z = -5.662, P < .001). Among the cohort, 27 patients (60.0%) responded to treatment, with 12 patients (44.44%) experiencing relapse during the follow-up period. The response rate (80.00%) of newly diagnosed ITP were significantly higher than of persistent ITP (28.57%) and chronic ITP (38.46%) (\x 2 = 9.560, P = .008) and the relapse rate of the newly diagnosed ITP (30.00%) was significantly lower than the persistent ITP and chronic ITP (100.00%, 80.00%) (\x2 = 6.750, P = .034). Notably, we found that the number of CD4+ T cells, duration of HIV infection, selection of HAART and type of glucocorticoids administered displayed no statistically significant effect on platelet count, treatment response, or relapse rate. However, we observed a significant decrease in platelet count in hepatitis C virus-positive individuals coinfected with HIV compared to those with HIV alone (Z = -2.855, P = .003). Our findings suggest that patients diagnosed with HIV and thrombocytopenia exhibit a low response rate to treatment and have an increased likelihood of relapse.

Synchronous multiple primary malignancies of clear cell renal cell carcinoma with sarcomatoid, thyroid carcinoma: a case report.

Multiple primary malignant neoplasms (MPMNs) are defined as the presence of two or more malignancies with different histologies in the same patient. MPMNs are rare, accounting for fewer than 4% of all tumor cases. Depending on the time interval between the diagnosis of the different malignancies, they are classified as either simultaneous or metachronous MPMNs, with simultaneous being rarer in MPMNs. Here, we present a 63-year-old female patient presenting with multiple primary renal and thyroid carcinomas and discuss the risk factors, treatment options, and prognosis of rare dual carcinomas. We focus on managing multidisciplinary teams and selecting individualized treatment options to deliver valuable treatment strategies to patients.

De-escalation or discontinuation of tyrosine kinase inhibitor in patients with chronic myeloid leukemia: A multicentral, open-label, prospective trial in China.

Background: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). Optimizing dose of tyrosine kinase inhibitors (TKIs) in the CML treatment maybe a new challenge to maintain effective and improving patients' quality of life. We hypothesized that administration of low-dose TKIs does not compromise major molecular response (MMR) in patients with CML who have a deep molecular response (DMR). Methods: We did an open-label, randomized trial at eight hospitals in China. Eligible CML-CP patients (aged 18-70 years) had shown continuous response to TKI more than 5 years and maintained MR4.5 (BCR-ABLIS ≤ 0.0032%) in recent 18 months. Patients were randomly assigned (1:1) to the TKI de-escalation group or the discontinuation group. Randomization was done with permuted blocks (block size four) and implemented through an interactive web-based randomization system. Recurrence was defined as the single sample with real time Quantitative PCR (RT-qPCR) measurement greater than 0.1% (MMR). The primary endpoint was 12-month MMR rate in patients who received de-escalation or discontinuation of TKIs. This study was registered at ClinicalTrials.gov (NCT04143087). Results: Around 125 patients were enrolled between October 23, 2019 and October 31, 2020, 62 patients received dose de-escalation of TKIs, while 63 patients in the discontinuation group. In the de-escalation group, molecular recurrence-free survival at 12 months was 88.32% (95% CI 79%-98%), whereas molecular recurrence-free survival in the discontinuation group at 12 months was 59.98% (95% CI 47-73). No progressions occurred at the data cut-off date. All 29 recurrence cases restart TKI treatment returned to MMR. Cytolytic NK cells as a proportion of lymphocyte cells were significantly increased from baseline after 6 months whether in the de-escalation or TKIs cessation group (P = 0.048, 0.001, respectively); compared with the relapsing patients, Tregs proportion was decreased (P = 0.003), and higher proportion of NK cells were found in non-relapsing patients whether in TKI de-escalation or discontinuation group (P = 0.011, 0.007, respectively). We also found that the de-escalation group showed better disease-specific HRQOL in regards to its impact on emotional functioning, fatigue, pain, and financial difficulties. Conclusion: With 88.32% MMR in 12-months follow-up after de-escalation TKIs' treatment, dose-halving could become a new treatment paradigm for CML patients who with DMR under continuing maintenance therapy with TKIs.

Integrative Genomic Analysis Reveals Cancer-Associated Gene Mutations in Chronic Myeloid Leukemia Patients with Resistance or Intolerance to Tyrosine Kinase Inhibitor.

INTRODUCTION: While the acquisition of mutations in the ABL1 kinase domain (KD) has been identified as a common mechanism behind tyrosine kinase inhibitor (TKI) resistance, recent genetic studies have revealed that patients with TKI resistance or intolerance frequently harbor one or more genetic alterations implicated in myeloid malignancies. This suggests that additional mutations other than ABL1 KD mutations might contribute to disease progression. METHODS: We performed targeted-capture sequencing of 127 known and putative cancer-related genes of 63 patients with CML using next-generation sequencing (NGS), including 42 patients with TKI resistance and 21 with TKI intolerance. RESULTS: The differences in the number of mutations between groups had no statistical significance. This could be explained in part by not all of the patients having achieved major molecular remission in the early period as expected. Overall, 66 mutations were identified in 96.8% of the patients, most frequently in the KTM2C (31.82%), ABL1 (31.82%), FAT1 (25.76%), and ASXL1 (22.73%) genes. CUX1, KIT, and GATA2 were associated with TKI intolerance, and two of them (CUX1, GATA2) are transcription factors in which mutations were identified in 82.61% of patients with TKI intolerance. ASXL1 mutations were found more frequently in patients with ABL1 KD mutations (38.1% vs 15.21%, P=0.041). Although the number of mutations was low, pairwise interaction between mutated genes showed that ABL1 KD mutations cooccurred with SH2B3 mutations (P<0.05). In Kaplan-Meier analyses, only TET2 mutations were associated with shorter progression-free survival (P=0.026). CONCLUSION: Our data suggested that the CUX1, KIT, and GATA2 genes may play important roles in TKI intolerance. ASXL1 and TET2 mutations may be associated with poor patient prognosis. NGS helps improving the clinical risk stratification, which enables the identification of patients with TKI resistance or intolerance in the era of TKI therapy.