A sensitive, rapid, simple and economical ultra-performance liquid chromatography–tandem mass spectro-metric method (UPLC–MS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0.05% ammonium acetate)and B(organic phase:acetonitrile)(A:B=40:60,v/v).The flow rate was 0.25 mL/min and the total run time was 6 min. The multiple reaction monitoring (MRM) transitions, m/z 494.5→394.5 for imatinib, 488.7→401.5 for dasatinib, 530.7→289.5 for nilotinib and 528.5→403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6–5250.0 ng/mL for imatinib, 2.0–490.0 ng/mL for dasatinib,and 2.4–4700.0 ng/mL for nilotinib.The method showed acceptable results on sensitivity,specificity, recovery, precision, accuracy and stability tests. This UPLC–MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentra-tions among the SLC22A5?1889T>C or SLCO1B3 699G>A genotypes(P>0.05).This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors(TKIs).

OBJECTIVE: To compare the effect and safety between Velcade-Dexamethasone (VD)and revised Vinorebine+Pirarubicin+ Dexamethasone (VAD) regiment for multiple myeloma (MM). METHODS: Thirty-six patients with MM were reviewed, 16 of whom were treated with VD (VD Group) and the others with VAD. European Group for Blood and Marrow Transplant (EBMT) criteria and National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) were chosen to analyze the efficacy and side effects. RESULTS: In the VD group and the revised VAD group, the rates of complete response, partial response, minimal response, no change and progress disease were 50% vs. 5%, 25% vs. 25%, 18.8% vs. 15%, 6.2% vs. 35% and 0 vs. 20%, respectively. The total response rates were 93.8% vs 45%. There was significant difference in the overall response rate between the 2 groups (P<0.05). The side effects were less serious, and the endurance was better in the VD group than those in the revised VAD group. No serious effects of hematology and cardiology were seen, and good endurance was showed in the renal dysfunction in the VD group. CONCLUSION Velcade combined with dexamethasone is a safe and effective regiment for multiple myeloma with good safety and endurance.
Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Boronic Acids ; administration & dosage ; adverse effects ; Bortezomib ; Dexamethasone ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; adverse effects ; Retrospective Studies

Objective To evaluate the clinical outcome of autologous hemopoietic stem cell transplantation (AHSCT) for hematological malignancies. Methods Data of 61 patients with hematological malignancies who underwent AHSCT in Xiangya Hospital from April 1994 to August 2008 were retrospectively analyzed. There were 30 acute non-lymphoblastic leukemias (ANLL), 25 non-Hodgkin lymphoma (NHL), 3 Hodgkin lymphoma (HL), and 3 plasmacytoma. Mel 160 mg/m2 + Ara-C 2.0/2.5 g × 2 +Cy 1.8 g/m2 × 2, or TBI 8-10 Gy + Cy 1.8 g/m2 × 2 were mainly included in pretreatment regimens. Results All patients had rapid hemopoietic reconstitution. There was one patient who died of heart failure during the transplantation process. The rate of AHSCT related death was 1.6 %. The median follow up duration was 52(2-211) months. Forty-seven of 61 patients were still alive during the analysis. The probabilities of disease free survival (DFS) at 5 years were significantly different between these two groups: (77.5±5.5) % for AHSCT groups and (31.6±7.3) % for synchronous intensive chemotherapy groups(P ＜0.01). Conclusion AHSCT can be safely performed as an important treatment constituent for hematological malignancies.

OBJECTIVE: To explore the clinical and pathologic features of angioimmunoblastic T-cell lymphoma(AITL) and provide evidence for diagnosis. METHODS: Eighteen AITL patients (9 males and 9 females aged from 14 to 70 years) were retrospectively analyzed in Xiangya Hospital of Central South University from July 2002 to September 2007. RESULTS: Characteristic features at the presentation of AITL included generalized lymphadenopathy, fever, splenomegaly, and skin rashes with polyclonal hyper-gammaglobulinemia and other hematological abnormalities (such as Coombs-positive hemolytic anemia), which often involved the bone marrow and had well-described histologic features. The positive rate for CXCL13 was 93.3%. CONCLUSION Repeated lymphadenbiopsy is helpful for AITL diagnosis. Routine histological and immunohistochemical examinations (especially including CXCL13) play significant role in the diagnosis and differential diagnosis of AITL.
Adolescent ; Adult ; Aged ; Chemokine CXCL13 ; metabolism ; Female ; Humans ; Immunoblastic Lymphadenopathy ; diagnosis ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; diagnosis ; metabolism ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVE: To explore the effect of trichostatin A (TSA) alone and combination with imatinib on the proliferation and apoptosis of K562R cells. METHODS: 3-(4,5-dimethylthiazol-2-yl) -5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay was used to observe the proliferation of K562R cells and apoptosis was analyzed by annexin-V/propidium iodide(PI) staining. RESULTS: After exposure to TSA, the proliferation of K562R cells was inhibited, and the effect was in both time- and dose-dependent manner. The apoptosis was induced. Combined with imatinib, the effect of proliferation inhibition was better. CONCLUSION TSA combined with imatinib can inhibit the proliferation of K562R cells and induce its apopotosis. TSA may become a new drug for imatinib-resistant patients.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Benzamides ; Cell Proliferation ; drug effects ; Drug Synergism ; Humans ; Hydroxamic Acids ; pharmacology ; Imatinib Mesylate ; K562 Cells ; Piperazines ; pharmacology ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology

OBJECTIVE: To retrospectively analyze the efficacy of three prognostic scoring systems on evaluating the prognosis for patients with chronic myeloid leukemia (CML) in chronic phase (CP).
 METHODS: In this retrospective cohort study, we collected 234 patients with CML in CP, who were treated with imatinib mesylate (IM). Patients were stratified into low-, intermediate- and high- risk groups according to three scoring systems (Sokal, Hasford and EUTOS), respectively. We compared the agreement of overall survival (OS), progression free survival (PFS), event free survival (EFS) in CML patients stratified by three prognostic scoring systems. The median for follow-up was 20.5 months. 
 RESULTS: EUTOS scoring system: In the low- and high-risk groups, the 5-year OS was 94.6% and 84.7% (P=0.011), 5-year EFS was 92.6% and 77.6% (P=0.001), and 5-year PFS was 95.3% and 82.4% (P=0.001), respectively. While stratified by Sokal or Hasford scoring system, there was no significant the correlation between low-, intermediate- and high- risk groups with the prognosis for CML patients (P>0.05). Compared with Sokal and Hasford scoring system, the outcome of EUTOS prognostic scoring system showed highly accordance with 5-year expect OS, PFS and EFS of CML patients.
 CONCLUSION EUTOS scoring system could predict the long-time outcome of CML-CP patients better than Sokal and Hasford scoring system. Chang of treatment may affect the prognostic value of EUTOS scoring system.
Disease-Free Survival ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Prognosis ; Retrospective Studies

OBJECTIVE: To study the efficacy of allogeneic hemotopoietic stem cell transplantation (allo-HSCT) for hematological malignancy. METHODS: A total of 104 patients with hematological malignancy, who underwent allo-HSCT in Xiangya Hospital from December 1999 to January 2010, were retrospectively analyzed. Of the patients, the transplantation related mortality (TRM), relapse rate (RR), 5-year overall survival (OS) and disease free survival (DFS) were estimated by Kaplan-Meier analysis. The unfavorable prognostic factors were also statistically examined. RESULTS: Hematopoietic reconstitution was achieved in 101 patients. At the last data of follow-up, the incidences of severe acute graft versus host disease (aGVHD) and extensive chronic GVHD were 15.38% and 25.53%, and the TRM and RR were 15.66% and 21.76%, respectively. The estimated 5-year OS and DFS for all patients were (73.49±4.59)% and (63.10±5.32)%, respectively. Those for acute myeloid leukemia (AML) patients were (63.00±9.51)% and (49.30±9.96)%, and those for chronic myeloid leukemia (CML) patients were (83.87±5.06)% and (74.55±6.79)%, respectively. The survival analysis suggested the poor prognostic factors for allo-HSCT recipients including female sex, severe aGVHD and refractory hematological malignancy. Further multivariate analyses revealed that severe aGVHD and refractory hematological malignancy were the independent risk factors of poor prognosis for the recipients (P<0.05). The 5-year DFS of severe aGVHD and refractory hematological malignancy patients was (48.22±12.69)% and (42.09±12.31)%, respectively. The TRM of severe aGVHD, HLA-mismatched graft and unrelated donor transplant was significantly higher than that of the corresponding control groups (57.14% vs. 4.81%, 33.33% vs. 10.41%, 26.09% vs. 9.28%; P<0.05). The RR of refractory hematological malignancy was significantly higher than that of the control group (41.09% vs. 15.63%, P<0.05). CONCLUSION The treatment of allo-HSCT can improve the disease free survival of patients with hematological malignany and is an important therapeutic method for hematological malignancy. Severe aGVHD and refractory hematological malignancy are the independent risk factors of poor prognosis for the allo-HSCT recipients with hematological malignancy.
Adolescent ; Adult ; Child ; China ; epidemiology ; Female ; Graft vs Host Disease ; epidemiology ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; therapy ; Leukemia, Myeloid, Acute ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Transplantation, Homologous ; Young Adult

OBJECTIVES: The number of gestational women has been increased in recent years, resulting in more adverse pregnancy outcomes. It is crucial to assess the coagulation function of pregnant women and to intervene in a timely manner. This study aims to analyze the influencing factors on thrombelastography (TEG) and explore the evaluation of TEG for gestational women. METHODS: A retrospective study was conducted on 449 pregnant women who were hospitalized in the obstetrics department in Xiangya Hospital of Central South University from 2018 to 2020. We compared the changes on the TEG parameters among normal pregnant women between different age groups, different ingravidation groups, and different stages of pregnancy groups. The influence on TEG of hypertensive disorders in pregnancy (HDP) and gestational diabetes mellitus (GDM) as well as two diseases synchronization was explored. RESULTS: Compared with the normal second trimester women, the R values and K values of TEG were increased, and α angle, CI values and LY30 values were decreased in third trimester women (all P<0.05). Compared with normal group, the R values and CI values of TEG of the HDP group have significant difference (both P<0.05). There were no significant difference of TEG between the GDM group, the HDP combined with GDM group and the normal group (all P>0.05). Multiple linear regression analysis showed that the influencing factors for R value in TEG were weeks of gestation (P<0.001) and mode of conception (P<0.05), for α angle was weeks of gestation (P<0.05), for MA value was mode of conception (P<0.05), and for CI value was weeks of gestation (P<0.05). The analysis of correlation between TEG with platelet (PLT) and coagulation routines represented that there was a correlation between TEG R values and activated partial thromboplastin time (APTT) (P<0.01), and negative correlation between TEG CI values and APTT (P<0.05). There was a negative correlation between TEG K values and FIB (P<0.05). The correlation of α angle (P<0.05), MA values (P<0.01) and CI values (P<0.05) with FIB were positive respectively. CONCLUSIONS The TEG parameters of 3 stages of pregnancy were different. The different ingravidation approach has effect on TEG. The TEG parameters were consistent with conventional coagulation indicators. The TEG can be used to screen the coagulation status of gestational women, recognize the abnormalities of coagulation and prevent the severe complication timely.
Female ; Humans ; Pregnancy ; Thrombelastography/methods* ; Blood Coagulation Tests/methods* ; Retrospective Studies ; Blood Coagulation ; Blood Platelets ; Diabetes, Gestational/diagnosis*