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

Adult ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy

Antineoplastic Agents/therapeutic use* ; Humans ; Imatinib Mesylate/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*

OBJECTIVETo explore demographic characteristics, current diagnosis and treatment patterns of chronic myelogenous leukemia (CML) patients in China.

METHODSData of hospitalized CML patients in 2005 whole year and outpatient information (July 1 through September 30, 2006) from 15 hospitals throughout China were analyzed.

RESULTSA total of 1824 CML cases were analyzed, including 722 inpatients and 1102 outpatients. The male/female ratio was 1.78:1. The median age at diagnosis was 40.02 (2.45 - 83.29) years old, 90.41% of the patients were diagnosed at chronic phase. Proportion of accelerated phase or blast crisis patients increased to 21.66% during study period. 93.20% of the patients received blood routine and bone marrow morphologic examination at diagnosis and in monitoring; 70.29% were performed cytogenetic analysis and 51.54% performed molecular measurement in addition. The most common therapy for CML treatment was hydroxycarbamide. The proportion of patients treated with imatinib and interferon was 37.45% and 25.55%, respectively. Of 722 inpatients, 164 (22.72%) received hemotopoietic stem cell transplantation (HSCT). The proportions of accelerated phase and blast crisis patients treated with imatinib were 48.28% and 48.42%, respectively, being significantly higher than that of chronic phase patients (35.9%) (P < 0.05). The mean imatinib dosage administered in the three phases patients did not differ significantly. Imatinib resistance rates were 6.87% and 16.28% for outpatient and inpatient, respectively. In the outpatient group, the primary resistance to imatinib occurred comparably to the secondary resistance (68.75%), while primary resistance was predominant in inpatient group (65.71%). The intolerance rates of imatinib for outpatient and inpatient were 3.21%, 11.63%, respectively. The majority of patients treated with imatinb were not monitored in time: 63.38% patients evaluated hematologic response after 3 months of treatment, proportions of patients received cytogenetic examination after 6 months and 12 months of treatment were 41.41% and 27.35%, respectively. Mean cost for HSCT was 213 092 +/- 125 890 RMB.

CONCLUSIONSCML in China tends to afflict younger population than in Western countries. Most patients were diagnosed in the chronic phase. Due to restriction of financial support, only one third of CML patients were treated with imatinib, and the majority of the treated were not monitored in time. Clinicians should pay attention to resistance and intolerance to imatinib treatment in accelerated phase or blast crisis patients.

Benzamides ; therapeutic use ; China ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Its pathogenesis is defined by mutations within the KIT and PDGFRα gene. Surgical resection is the only radical treatment at present, but recurrence is common. In recent years, targeted therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. For resectable GIST, operation combined with neoadjuvant and adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors can improve the prognosis of high-risk patients before or after complete resection. For unresectable GIST, targeted therapy with imatinib mesylate can effectively inhibit and ameliorate the progression of GIST.
Benzamides ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; surgery ; therapy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; therapy ; Humans ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use

Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal tumor of the gastrointestinal tract. With decades of development, surgical excision combined with molecular targeted agents is becoming the mode for the GIST treatment. Imatinib mesylate (IM) is the first-line therapy medicine for GIST adjuvant treatment, and it significantly reduces recurrence or metastasis and increases survival. According to the recently results of SSGXVIII/AIO study, imatinib adjuvant therapy should be administered for at least 3 years for the GIST patients with a high estimated risk of recurrence and metastasis after surgery. Nevertheless, the optimal duration of the adjuvant therapy or the follow-up policy remains unclear, and we look forward to standard assessment criteria for individualized treatment.
Benzamides ; therapeutic use ; Chemotherapy, Adjuvant ; Gastrointestinal Neoplasms ; drug therapy ; surgery ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use

Currently, the treatment of recurrent or metastatic gastrointestinal stromal tumor(GIST) has become a tremendous challenge. Some international clinical trials revealed that imatinib might significantly improve the survival of patients with recurrent or metastatic GIST. Though the combination of surgery and imatinib has become an ideal treatment of metastatic GIST, there still exist some controversies regarding how to combine the two methods. Imatinib may influence the blood coagulation mechanism, therefore it is suggested that imatinib cessation should be performed a week before operation. Cytoreductive surgery has some clinical effects on recurrent or metastatic GIST, which can be combined with targeted therapy. Furthermore, the clinical trial for recurrent or metastatic GIST needs further evaluation.
Benzamides ; administration & dosage ; therapeutic use ; Combined Modality Therapy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; Piperazines ; administration & dosage ; therapeutic use ; Pyrimidines ; administration & dosage ; therapeutic use

Objective: To compare the cytogenetic and molecular responses, outcomes and severe hematologic toxicity of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: Newly diagnosed CML-CP patients were consecutively recruited from January 2006 to December 2018 who received nilotinib and imatinib as first-line treatment. Clinical data were retrospectively analyzed. Results: A total of 524 patients were classified into 439 (83.8%) receiving imatinib and 85 (16.2%) receiving nilotinib. Comparing with imatinib group, patients in nilotinib group were much younger (P=0.019) and more with intermediate and high Sokal risks (P<0.001) , WBC ≥100×10(9)/L (P<0.001) , HGB<120 g/L (P<0.001) , blast cells in bone marrow (P=0.026) , splenomegaly (P<0.001) by physical examination at diagnosis, and longer interval from diagnosis to TKI treatment (P=0.003) . With a median TKI duration of 57 (range 3-153) months, the probabilities of complete cytogenetic response (CCyR) (P=0.011) , major molecular response (MMR) (P=0.001) and MR(4.5) (P=0.046) were much higher in nilotinib group than those in imatnib according to each risk group. There is no statistical significance on probabilities of failure free survival (FFS) , progression free survival (PFS) and overall survival (OS) at 6 years between the two groups. Multivariate analyses showed that imatinib was an adverse factor associated with achieving CCyR (OR=0.6, 95% CI 0.5-0.8, P=0.001) , MMR (OR=0.6, 95% CI 0.5-0.9, P=0.032) and MR(4.5) (OR=0.6, 95%CI 0.5-0.9, P=0.032) and poor FFS (OR=1.9, 95%CI 1.0-3.4, P=0.041) . In addition, Sokal score was an independent factor affecting cytogenetic and molecular responses, treatment failure, disease progression and survival. Male, WBC ≥100×10(9)/L or HGB<120 g/L at diagnosis were significantly associated with lower cytogenetic and molecular response rates and/or poor FFS. The severe hematologic adverse events were not associated with different TKIs. Conclusions: Nilotinib reaches to the faster and deeper cytogenetic and molecular responses and significantly improves FFS than imatinib in newly diagnosed patients with CML-CP.
Antineoplastic Agents/therapeutic use* ; Humans ; Imatinib Mesylate/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Male ; Protein Kinase Inhibitors ; Pyrimidines/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Objective: To analyze the correlation between plasma trough level of generic imatinib and its metabolism and clinical outcomes in Chinese patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: The 21 patients with CML-CP who enrolled in a clinical trial YMTN 1.0 from Oct 11(th), 2012 to May 8(th), 2013 and received generic imatinib were as study subjects. The correlation between steady plasma trough levels of imatinib and its metabolism with clinical response, age, weight and body surface area (BSA) were evaluated. Results: ①The mean steady plasma trough level of generic imatinib and its metabolism was (1 185.07±417.91) μg/L and (251.53±76.50) μg/L, respectively. ②Age, weight and BSA has no significant effects on plasma trough level of generic imatinib and its metabolism (P>0.05) . ③Patients with steady plasma trough level of generic imatinib more than 1 000 μg/L are possible to have higher major molecular response (MMR) /complete molecular response (CMR) rate than those below 1 000 μg/L (42% vs 0, P<0.05) . Conclusion: Plasma trough levels of generic imatinib varied in CML patients. The steady plasma trough levels of generic imatinib is maybe related to molecular response in CML patients.
Antineoplastic Agents ; Humans ; Imatinib Mesylate/therapeutic use* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; 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