OBJECTIVETo investigate the chronic hepatic damage in acute promyelocytic leukemia (APL) patients long-term treated with tetra-arsonic tetra-sulfide (As(4)S(4)).

METHODSThe periodical liver biochemical examinations and ultrasonography results and hepatic fibrosis indicators (P III NP and type IV collagen) of patients were analysed.

RESULTS106 APL patients treated with As(4)S(4), the median follow-up time was 36 months (6 - 72). The HCV(-) group includes 84 APL patients. During the first course the abnormal rate of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was 16.7% and 14.5% (higher than the two times of the normal value), the ALT, AST, gamma-glyoxylate aminotransferase (GGT) levels during the first course were statistically higher than As4S4 treatment before (P < 0.05). There were no statistically differences between the ALT, AST, GGT levels after and before treating with As(4)S(4) in half a year, one year, two year, more than three years (P > 0.05). Other biochemical indicators such as ALP, LDH, TBIL, DBIL, TP, ALB, A/G, BUN, CRE, there were no significantly differences before and after As(4)S(4) treatment (P > 0.05). The HCV(+) group includes 22 APL patients, during the first course, the abnormal rate of the ALT, AST were 63.6% and 59.1%, but at the 2 year, more than 3 years there were no significantly differences compared with As(4)S(4) treatment before (P > 0.05). 42 APL patients were treated with As(4)S(4) more than 3 years, in 33 HCV(-) APL patients, two APL patients had splenomegaly, one APL patient's breadth of the portal vein was wider than 1.4 cm, 21 APL patients had fatty liver (63.6%). The hepatic fibrosis indicators of the 16 APL patients were all normal. In 9 HCV(+) APL patients, 4 APL patients had splenomegaly, 2 APL patients, breadth of portal vein were wider than 1.4 cm, 6 APL patients had fatty liver (66.7%). 6 patients were examined with the hepatic fibrosis indicators, 2 patients, were higher than the normal value.

CONCLUSIONLong term As(4)S(4) treatment for APL patients had no obvious effects on hepatic function, no obvious hepatic fibrosis and portal hypertension signs at more than 3 years, excepting for the rate of fatty liver was high.

Adolescent ; Adult ; Aged ; Arsenicals ; adverse effects ; chemistry ; Collagen Type IV ; metabolism ; Fatty Liver ; chemically induced ; metabolism ; Female ; Fibrosis ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Liver ; drug effects ; pathology ; Male ; Middle Aged ; Sulfides ; adverse effects ; chemistry ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of imatinib in the treatment of adult patients with chronic granulocytic leukemia (CGL) in accelerated phase.

METHODSThirty patients with CGL in accelerated phase were orally administered with imatinib 400 or 600 mg daily for 7 approximately 9 months.

RESULTSHematological responses occurred in 28 of 30 patients (93.3%) in the treatment: 14 (46.7%) had a complete hematological response, 10 (33.3%) had a marrow response, and 4 (13.3%) returned to chronic phase. Bone pain and splenomegaly disappeared soon after the administration of imatinib. Eight patients relapsed 30 approximately 172 days after hematological responses. Six of them received imatinib with daily dose increment to 800 mg. Four of these 6 patients had no response and 2 returned to chronic phase again. The risk factors for relapse were blasts > or = 15% in bone marrow or in peripheral blood, extramedullary leukemia involvement, hemoglobin < 100 g/L before the administration of imatinib, and lack of a complete hematological response after the treatment. Cytogenetic remission occurred in 6 of 27 patients (21.4%) after 3 months treatment: 4 (14.3%) were complete cytogenetic response and 2 (7.1%) major cytogenetic response. Mild non-hematologic adverse effects occurred in most of the patients, but were manageable and tolerable, or disappeared automatically. Severe neutropenia or thrombocytopenia appeared in more than half of the patients.

CONCLUSIONSImatinib has substantial activity and is well-tolerated in the treatment of accelerated phase of CGL.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Treatment Outcome

OBJECTIVESTo assess bone marrow morphologic changes in Philadelphia-chromosome positive chronic myeloid leukemia (Ph(+)-CML) patients treated with Imatinib, and to evaluate the correlation of the morphologic changes with hematological or cytogenetic responses.

METHODSOne hundred and seventeen patients with Ph(+) CML: 54 in chronic phase but failed to interferon-alpha treatment, 41 in accelerated phase, 22 in blastic phase received oral administration of Imatinib 400 or 600 mg once daily for more than 18 months.

RESULTSAll of the patients responded to the treatment, including complete hematological response, bone marrow response and return to chronic phase, bone marrow cellularity and myeloblast count reduced significantly to non-CML picture. Myeloid/erythroid ratio and megkaryocyte count were decreased significantly in most patients in chronic and accelerated phases (P < 0.05). Bone marrow hypoplasia or aplasia was associated with lower cytogenetic response rates in patients in chronic phase (58.8% vs 86.5%, P = 0.035), lower complete hematological response in patients in accelerated phase (26.3% vs 75.0%, P = 0.004), and 6-month overall survival in patients in blastic phase (77.8% vs 16.7%, P = 0.009). Patients in advanced stage obtained non-CML marrow picture in 1 month of treatment had better prognosis. 18-month disease progression rates were lower (25% vs 75%, P = 0.028) and overall survival rates higher (75.0% vs 11.8%, P = 0.004) in patients obtained non-CML picture marrows than in those with CML marrows picture in accelerated phase. Hematological response rate and overall survival of more than 6 months were higher in patients with non-CML marrows picture than those with CML marrows picture (100.0% vs 40.0%, P = 0.017 and 83.3% vs 26.7%, P = 0.046 respectively) in blastic phase.

CONCLUSIONSNormal marrow appearance can be sustained under continuous treatment of Imatinib in CML patients who achieved hematological responses.

Adolescent ; Adult ; Aged ; Benzamides ; Bone Marrow Cells ; cytology ; drug effects ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; pathology ; Male ; Middle Aged ; Piperazines ; administration & dosage ; pharmacology ; Pyrimidines ; administration & dosage ; pharmacology ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate clonal evolution of abnormal Philadelphia chromosome-negative cells (Ph- CE) after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).

METHODSBone marrow cells G-banding karyotype was evaluated every 3 months in 100 patients with Ph+ CML after achieving hematologic responses on the course of imatinib therapy. There were 54 patients in chronic phase (CP), 37 in accelerated phase (AP) and 9 in blast phase (BP).

RESULTSAfter a median follow-up of 32 months (ranged 25-34 months), 11 patients, including 5 cases in CP, 5 in AP and 1 in BP, developed transient, interrupted or continuous Ph- CE after 3 - 29 months on imatinib therapy. Ph- CE emerged at the beginning of Ph+ cells decreasing or after Ph+ cells disappearing. The proportion of Ph- CE, was negatively correlated with the proportion of Ph+ cells (P < 0.05). Ph- CE commonly included +8 (45.5%) and +Y (27.3%). Five patients had additional cytogenetic abnormalities besides Ph+ in Ph- CE. Seven of the patients with Ph- CE achieved a major cytogenetic response while 9 of them achieved a complete hematologic response. One patient with Ph- CE in AP progressed to BP 20 months after the initiation of the therapy while the rests remained in hematologic or cytogenetic responses.

CONCLUSIONPh- CE occurred in about 11% of the patients with Ph+ CML who achieved major or minor cytogenetic responses on imatinib therapy. After a median follow-up of more than 2 years, most of the patients with Ph- CE were in a stable status with no disease progression.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Clone Cells ; drug effects ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; pathology ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Philadelphia Chromosome ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of Gleevec (Imatinib) in the treatment of patients with Ph positive chronic myeloid leukemia in chronic phase (CML-CP).

METHODSA total of 54 CML-CP patients in whom previous therapy with interferon-alpha had been failed or untolerated, or relapsed after allogeneic stem cell transplantation (allo-SCT) were treated with 400 mg/d of oral Gleevec for 6 to 11 months.

RESULTFifty-three patients being able to evaluate achieved complete hematological response within 7 to 28 days. Fifty-two (98%) of them remained in this situation at last follow-up. One patient relapsed after 7 months' treatment, and progressed to accelerated phase. Gleevec induced major cytogenetic response in 37 patients (70%) and complete cytogenetic response in 27 (51%). Twenty-nine of 37 patients (78%) achieved major cytogenetic response within 3 months. Grade 3 neutropenia or thrombocytopenia occurred in about 10% of patients, which were manageable or tolerated. Grade 3 or 4 nonhematologic adverse effects were infrequent. Only 1 patient (2%) discontinued treatment because of drug-related adverse events.

CONCLUSIONSGleevec induced high rate of cytogenetic and hematologic responses in patients with CML-CP who failed in previous interferon therapy. The adverse effects were mild and manageable, or no need for treatment.

Adolescent ; Adult ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Male ; Middle Aged ; Piperazines ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use

Objective To observe the effect of ginsenoside Rb1,the most abundant ginsenoside in ginseng root,on differentiation and lipolysis of 3T3-L1 cells and to explore its anti-diabetic mechanism.Methods 3T3-L1 preadipoeytes were induced under standard differentiation process in the presence of 0.1,1,10,100?mol/L ginsenoside Rb_1 for 6 days.Oil red O staining,measurement of triglyceride contents and glucose uptake assay were performed.The expressions of mRNA and protein of PPAR?2,C/EBP?,ap2,glucose transporter (Glut) 1,and Glut4 were analysed with quantitative real time-PCR and Western blot.The binding affinity of Rb_1 to PPAR?-LBD was evaluated by Surface Plasmon Resonance (SPR).Lipolysis of adipocytes was examined by the measurement of glycerol released from adipoeytes treated with Rb_1 for 1 h.Results Ginsenoside Rb_1 facilitated differentiation of 3T3-L1 preadipoeytes in a dose-depondent manner.10?mol/L ginsenoside Rb_1 increased lipid accumulation by about 56%.Treatment of differentiating adipocytes with 10?mol/L ginsenoside Rb_1 increased the expressions of PPAR?2 and C/EBP?mRNA and protein,as well as mRNA expression of ap2,one of their target genes.After treatment of differentiating adipoeytes with Rb_1,basal and insulin-mediated glucose transport augmented significantly accompanied by up-regulations of mRNA and protein level of Glut4,but not of Glutl.SPR showed Rb_1 could bind to PPAR?which suggested Rb_1 was a ligand of PPAR?.Ginsenoside Rb_1 inhibited basal lipolysis in adipoeytos in a dose-dependent manner.However,it did not affect isoproterenol-stimulated lipolysis.Conclusion As a PPAR?ligand,ginsenoside Rb_1 promotes adipogenesis,inhibitas basal lipolysis and inereasos basal and insulin-mediated glucose transport in cultured adipoeytes.Therefore,anti-diabetic and insulin-sensitizing activity of ginsenosides is,at least in part,involved in the enhancing effect on PPAR?2 and C/EBP?expressions,hence promoting adipogenesis and glucose uptake,and inhibiting lipolysis in adipocytes.

OBJECTIVETo evaluate the effect of tetra-arsenic tetra-sulfide (As4S4) therapy on the corrected QT interval (QTc) in the acute promyelocytic leukemia (APL) patients.

METHODSNinety cases of APL treated with As4S4 were divided into two groups--the remission induction group and maintenance therapy group. Blood arsenic concentration was measured and a 12-lead electrocardiogram (ECG) was simultaneously performed before treatment and after remission in the induction group, and before and 2, 4, 6, 8, 10 courses after the treatment in the maintenance therapy group. QT interval on each ECG was measured and corrected by the Bazett formula.

RESULTSOral administration of As4S4 could lead to the prolongation of QTc both in remission induction and maintenance therapy groups. QTc prolongation was related to the doses of As4S4 and blood arsenic levels. QTc prolongation and its variation range were increased with accumulative doses of As4S4 and the blood arsenic levels. In ten courses maintenance therapy patients, the average abnormal rate of QTc was 37.7%. Blood arsenic concentration was increased slowly with courses, but the variation had no statistical difference (P > 0.05). All the patients whose QTc was abnormal (> or = 440 ms) had neither symptoms nor serious cardiac events, such as ventricular tachycardia and Torsade de pointes and could complete the As4S4 therapy.

CONCLUSIONAlthough As4S4 therapy can lead to QTc prolongation in the treatment of APL patients, it does not preclude the completion of the therapy.

Adolescent ; Adult ; Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Electrocardiography ; drug effects ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; physiopathology ; Male ; Middle Aged ; Sulfides ; pharmacology

The objective of this study was to investigate arsenic absorption and retention in acute promyelocytic leukemia (APL) patients treated with tetra-arsenic tetra-sulfide (As(4)S(4)). Arsenic concentrations in samples from APL patients were quantitatively determinated by Hydride Generation Atomic Absorption Spectrometry. The results showed that blood arsenic level was 51.7 +/- 18.7 microg/L (n = 41), urine arsenic level was 2359.1 +/- 1910.6 microg/L (n = 36), and the average daily urinary arsenic excretion was 5.1 +/- 4.06 mg/day (n = 32) on the 7th-9th day after As(4)S(4) administration; blood arsenic level was 61.7 +/- 22.7 microg/L (n = 30), urine arsenic level was 2834.0 +/- 1958.3 microg/L (n = 27), the average daily urinary arsenic excretion was 6.3 +/- 4.98 mg/day (n = 24) on the 10th-12th day after As(4)S(4) administration; blood arsenic level was 62.8 +/- 25.1 microg/L (n = 34), urine arsenic level was 2859.3 +/- 2298.2 microg/L (n = 32) and the average daily urinary arsenic excretion was 6.82 +/- 5.58 mg/day (n = 32) on the 13th-15th day after As(4)S(4) administration. Blood arsenic level was 20.7 +/- 10.9 microg/L (n = 31), urine arsenic level was 525.5 +/- 337.1 microg/L (n = 28), and the average daily urinary arsenic excretion was 1.76 +/- 1.3 mg/day (n = 17) on the 7th-9th day after stop of treatment; blood arsenic level was 16.1 +/- 10.1 microg/L (n = 34), urine arsenic level was 207.1 +/- 164.5 microg/L (n = 28) and the average daily urinary arsenic excretion was 0.42 +/- 0.27 mg/day (n = 22) on the 13th-15th day after stop of treatment. Blood arsenic concentration, urine arsenic concentration and daily urinary arsenic excretion reach a steady state after treatment with As(4)S(4) for 10 days. The average urinary arsenic excretion was 6.82 +/- 5.58 mg/day (n = 32), arsenic absorption level was 9.74 +/- 7.97 mg/day and arsenic absorption efficiency was 0.25 +/- 0.20% during treatment. In conclusion, the majority of absorbed arsenic was excreted from urine and other ways, only a small part of absorbed arsenic was retained in body at the 14th day after therapy was discontinued, blood arsenic concentration, urine arsenic concentration, daily urinary arsenic excretion and hair arsenic concentration could be considered as useful biomarkers for monitoring arsenic absorption and retention in APL patients treated with As(4)S(4).
Absorption ; Antineoplastic Agents ; pharmacokinetics ; therapeutic use ; Arsenic ; pharmacokinetics ; Arsenicals ; pharmacokinetics ; therapeutic use ; Hair ; metabolism ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; metabolism

OBJECTIVETo investigate the relationship between the biological features and the treatment efficacy and prognosis in acute myeloid leukemia subtype M2 (AML-M2) patients with chromosome 8 and 21 translocation.

METHODSBy using Cox regression model and Kaplan-Meier analyses, prognostic factors in 54 cases of de novo adult AML with t(8;21) in our institute from 1990 to 2003 were retrospectively analyzed.

RESULTThe complete remission (CR) rates were 81.9% for all M2 patients, 82.4% for patients with normal karyotype, 88.5% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], 100.0% for 28 patients with t(8;21) alone and 75.0% for 24 patients with additional chromosome abnormalities (P < 0.01). The actuarial 3 year overall survival(OS) was 26% for M2 patients with normal karyotype, 25% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], in whole t(8;21) group, 46.4% for patients with t(8;21) alone and 0% for patients with additional chromosome abnormalities (P < 0.01). Multivariate analysis of prognostic factors showed that chromosome abnormalities besides t(8;21) was the only factor affecting CR, disease-free survival (DFS) and OS. DFS of allogeneic hematopoietic stem cell transplantation (HSCT) and intermediate-dose cytarabine/high dose cytarabine (IDAC) groups were better than the group received routine dose cytarabine as postremission therapy (P < 0.01).

CONCLUSIONAML with t(8;21) is not a single defined AML subset, and patients with additional chromosome abnormalities have a worse prognosis. HSCT and IDAC could improve the outcome. HSCT is the best choice for patients with high risks, especially with additional chromosome abnormalities.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; surgery ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Translocation, Genetic

OBJECTIVETo evaluate the indications and surgical procedure of bronchial and pulmonary artery sleeve resection for patients with centrally located non-small cell lung cancer, and how to prevent complications.

METHODSFrom July 1989 to Aug 2000, 32 cases of central NSCLC were treated with bronchial and pulmonary arterial sleeve resection and reconstruction. The results were retrospectively analyzed.

RESULTSThe complication rate was 25.0% (8/32), the mortality rate in 30-day postoperation was 6.3% (2/32), the overall 1-, 3- and 5-year survival rate was 82.8% (24/29), 50.0% (11/22) and 33.3% (4/12), respectively.

CONCLUSIONBronchial and pulmonary arterial sleeve resection and reconstruction in the treatment of patients with central NSCLC can not only maximize preservation of functional pulmonary parenchyma and improve patients, quality of life, but also provide an opportunity for those patients with poor pulmonary function to receive surgical resection of the tumor.

Adult ; Aged ; Bronchi ; surgery ; Carcinoma, Non-Small-Cell Lung ; surgery ; Female ; Humans ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Pulmonary Artery ; surgery ; Reconstructive Surgical Procedures