No abstract available.
Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Humans ; Piperidines/*therapeutic use ; Pyrimidines/*therapeutic use ; Pyrroles/*therapeutic use

Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.
Humans ; Lymphoma, B-Cell/drug therapy* ; Piperidines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use*

Bibenzyls/*chemical synthesis ; Bibenzyls/therapeutic use ; Imidazoles/*chemical synthesis ; Imidazoles/therapeutic use ; Pyrimidines/*chemical synthesis ; Pyrimidines/therapeutic use ; Sarcoma 180/drug therapy

Imatinib mesylate has been commonly used in the treatment of patients with chronic myeloid leukemia (CML). However, a significant number of CML patients treated with imatinib developed thrombocytopenia, oligocythemia, granulocytopenia. It has been confirmed that imatinib not only inhibits BCR-ABL mutations, but also suppresses other tyrosine kinase receptor genes such as PDGFR, JAK2V617F and C-KIT mutations, providing an important potential of targeted therapy for myeloproliferative disease. As the PDGFR, JAK2 and C-KIT play important roles in the regulation of hematopoiesis, suggesting that imatinib may block the phosphorylation of PDGFR, JAK2V617F and C-KIT receptors, interrupt the signal transduction cascades, disrupt cell differentiation and proliferation. In this review, the application and the potential molecular mechanism of imatinib in the treatment of thrombocythemia and other myeloproliferative diseases are discussed.
Benzamides ; therapeutic use ; Humans ; Imatinib Mesylate ; Myeloproliferative Disorders ; drug therapy ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Thrombocytosis ; drug therapy

OBJECTIVE: To evaluate the efficacy of the second-line nilotinib and third-line dasatinib on chronic myelogenous leukemia (CML) with failed first- and second-line treatments, and analyze the influencing factors of the efficacy. METHODS: Selected 83 patients in The Third People's Hospital of Kunshan City, Jiangsu Province with CML who were treated with nilotinib as the second-line treatment after the failure of the first-line treatment with imatinib as the second-line treatment group (referred to as the second-line group) from January 2014 to December 2018, and 61 CML patients who were treated by dasatinib as the third-line treatment group (referred to as the third-line group) after the failure of the second-line treatment with nilotinib; the first-line treatment with imatinib failed, but due to various reasons, the patients were fully after being informed of the possible serious consequences of not changing the drug treatment, 37 CML patients who were still required to continue imatinib treatment served as the control group. The hematological, genetic and molecular responses of each group were compared for 3, 6, and 24 months of treatment. LogistiC regression was used to analyze the factors affecting the second and third line curative effects. RESULTS: The three groups had statistically significant differences in the rates of achieving CHR, MCyR, and MMR at 3, 6, and 12 months of treatment (P<0.05). Compared the two groups, the CHR rates of the second-line group at 3, 6, and 12 months of treatment were 100.00%, 97.59%, and 95.18%, respectively; higher than the third-line group's 90.16%, 86.89%, 83.61% and the control group's 83.78%, 75.68% and 72.97%; the CHR rate of the third-line group was higher than that of the control group at 6 and 12 months of treatment. The rates of reaching MCyR at 3, 6, and 12 months after treatment in the second-line group were 87.95%, 93.98% and 93.98%, respectively, while those in the third-line group were 80.33%, 88.52% and 86.89%, which were higher than those of the control group of 67.57%, 64.86% and 48.65%. The rates of achieving MMR at 3, 6, and 12 months of treatment in the second-line group were 19.28%, 33.72% and 60.24%, respectively, and those in the third-line group were 11.48%, 26.23% and 49.18%, which were higher than those of the control group of 0.00%, 2.70% and 0.00%; The rate of reaching MMR within 12 months of treatment in the second-line group was higher than that of the third-line group, and the differences was statistically significant (P<0.05). There was no significant difference in the rate of reaching MCyR between the second-line group and the third-line group at 3, 6, and 12 months, and the rate of reaching MMR at 3 and 6 months (P>0.05). The incidence of nausea and vomiting among the three main non-hematological adverse reactions, and the incidence of grade 1~2 anemia among the hematological adverse reactions were statistically significant (P<0.05). There was no significant difference in the incidence of rash, eyelid edema, diarrhea, thrombocytopenia, leukopenia and neutropenia in the three groups (P>0.05). The incidence of nausea and vomiting and grade 1~2 anemia in the second-line group and the third-line group were higher than that of the control group, and the difference was statistically significant (P<0.05). There were statistically significant differences in Sokal score, medication compliance, and hematological adverse reactions between the MMR group and the non-MMR group (P<0.05). Logistic regression analysis showed that dose reduction or withdrawal during the treatment period, and grade 3~4 hematological adverse reactions were the main factors affecting the second and third line curative effects (OR=22.160, 2.715, 95% CI=2.795-93.027, 1.882-48.834). CONCLUSION The second-line nilotinib and the third-line dasatinib have a better effect on CML patients who have failed the first and second-line treatments. Grade 3~4 hematological adverse reactions, dose reduction or withdrawal are risk factors that affect the efficacy of second and third-line treatments.
Antineoplastic Agents/therapeutic use* ; Dasatinib/therapeutic use* ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors/therapeutic use* ; Pyrimidines/therapeutic use* ; Treatment Outcome

Gastrointestinal stromal tumor(GIST) originates from interstitial cells of Cajal(ICCs). Tyrosine kinase inhibitors(TKI) such as imatinib and sunitinib, are effective agents besides surgery. However some GIST can become primarily or secondarily resistant to those drugs. The difference in gene mutation types and secondary gene mutation is the main cause. When the GIST is proved to be drug resistance, reasonable personal treatment strategies based on individualized medicine should be made to improve outcomes and quality of life.
Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Drug Resistance, Neoplasm ; genetics ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; Humans ; Imatinib Mesylate ; Indoles ; therapeutic use ; Piperazines ; therapeutic use ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines ; therapeutic use ; Pyrroles ; therapeutic use

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.
Dasatinib/therapeutic use* ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Pyrimidines/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Antineoplastic Agents ; Dasatinib ; Humans ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Protein Kinase Inhibitors ; Pyrimidines/therapeutic use*

Humans ; Leukemia, Myelomonocytic, Chronic/drug therapy* ; Nitriles ; Pyrazoles/therapeutic use* ; Pyrimidines

BACKGROUNDIn our clinical practice we have been attracted by a group of patients with airway aspergillosis who have airway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial aspergillosis (PNTA). In this study we analyzed the clinical data from patients with PNTA, so as to guide the diagnosis and treatment of the disease.

METHODSA total of 16 PNTA patients were treated in Changhai Hospital from January 2000 to January 2009. Their clinical data, including the demographic information, clinical symptoms, imaging findings, bronchoscopy findings, treatment strategies and efficacy, and prognosis, were retrospectively analyzed.

RESULTSAll 16 patients were found to have primary systemic immunodeficiency diseases and/or damage of the focal airways. Nine patients (9/16, 56.3%) had pulmonary and tracheobronchial tumors, 5/16 (31.3%) had tracheobronchial involvement secondary to non-pulmonary tumors, and 2/16 (12.5%) had lung transplantation. The most common causes of PNTA included local radiotherapy (10/16, 62.5%), repeated chemotherapy (7/16, 43.8%) and recurrent intervention therapy by bronchoscope (4/16, 25.0%). Aspergillus fumigatus was the most frequent pathogen (62.5%, 10/16). The main clinical manifestations included progressive dyspnea (14/16, 87.5%) and irritable cough (12/16, 75.0%). The trachea was involved in 9/16 patients (56.3%), right main bronchus in 10/16 (62.5%). All 16 patients were treated with systemic anti-aspergillosis agents, local anti-aspergillosis agents with amphotericin B inhalation and direct perfusion of amphotericin B by bronchoscope, and interventional treatment by bronchoscope to ensure an unobstructed airway. The total efficiency was 31.3%.

CONCLUSIONSPNTA is an infectious disease caused by aspergillus and it mainly involves the trachea, primary bronchus and segmental bronchus. A. fumigatus is the most common pathogen. PNTA can pose a severe clinical threat and often occurs after systemic immunodeficiency and/or local airway damage, with the main symptoms including dyspnea and irritable cough. Bronchoscopic findings supply the main evidence for diagnosis of PNTA. Treatment of PNTA is difficult and requires a long course. Systemic and local anti-aspergillosis agents plus bronchoscopy debridement can improve the prognosis of the disease.

Adult ; Aged ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Aspergillosis ; diagnosis ; drug therapy ; Bronchoscopy ; Echinocandins ; therapeutic use ; Female ; Humans ; Itraconazole ; therapeutic use ; Lipopeptides ; Lung Diseases, Fungal ; diagnosis ; drug therapy ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Triazoles ; therapeutic use ; Voriconazole