[Relationship of Expression Between SOX11 and PAX5 in Pathological Tissue Specimens of Patients with Mantle Cell Lymphoma and Its Clinical Significance].

OBJECTIVE: Investigate the expression of SRY-related HMG box 11 (SOX11) and paired box domain 5 (PAX5) in patients with mantle cell lymphoma (MCL) and analyze the relationship between them and their clinical significance. METHODS: Seventy-six formalin-fixed paraffin-embedded (FFPE) samples of patients who were diagnosed with MCL from January 2012 to August 2017 were collected．Fifty-six FFPE samples from patients with diffuse large B cell lymphoma (DLBCL), thirty-eight FFPE samples from patients with follicular lymphoma (FL) and nine FFPE samples from patients with Burkitt's lymphoma (BL) were used as control groups. Real-time quantitative PCR (qRT-PCR) and immunohistochemistry were used to detect the mRNA and protein expressions of SOX11 and PAX5. The association between expressions of SOX11 and PAX5 in patients with MCL was analyzed. On the basis of the median H score of SOX11 and PAX5 protein expressions in patients with MCL, they were divided into high and low expression group, and the relationship between the different groups and patients' clinical characteristics and prognosis were analyzed. RESULTS: The different mRNA expression levels of SOX11 and PAX5 in different lymphoma tissues were statistically significant ( P<0.01). The mRNA expression levels of SOX11 and PAX5 in MCL group were higher than those of the control groups, and the differences of those between MCL and DLBCL or FL were statistically significant ( P<0.01). However, the differences of those between MCL and BL were not significant ( P>0.05). The expression level of SOX11 protein was also higher than those of the control groups ( P<0.000 1). However, there was no significant difference in PAX5 protein expression level between the MCL group and the control group, nor the expression levels of SOX11 and PAX5 genes and proteins among the control groups ( P>0.05). By analyzing the samples from patients with MCL, we observed a positive relevance between SOX11 and PAX5 both in mRNA expression level ( r s=0.714, P<0.000 1) and protein expression level ( G=0.407, P=0.01). There was no difference in clinical characteristics and overall survival between the high and low expression group. CONCLUSION: In MCL, there was a positive relevance between the expressions of SOX11 and PAX5. The expression of SOX11 or PAX5 alone has no significant effect on the prognostic stratification of MCL patients.

[The Value of Circulating Exsomal miR-451a to Monitor Therapy Response in Diffuse Large B Cell Lymphoma].

OBJECTIVE: To investigate the expression level of circulating exsomal miR-451a and its significances in therapy monitoring in diffuse large B cell patients. METHODS: We isolated exsomal RNAs fractions from serum of 56 DLBCL patients before treatment,during treatment and after treatment. The serum of 56 healthy controls was collected at the same time. Quantitative real time polymerase chain reaction (qRT-PCR) were performed to detected the expression level of circulating exsomal miR-451a. Receive operater characteristic (ROC) curve was performed to comfirm the diagnostic efficiency of miR-451a. Chemotherapy effect corresponding with miR-451a was analyzed. RESULTS: Circulating exsomal miR-451a was down-expression in DLBCL compared with healthy controls (P<0.000 1), and the area under the ROC curve (AUC) was 0.737 (95%CI0.645-0.816) . In 43 patients who had complete follow-up information,the patients who obtained remission,including complete remission (CR) and partial remission (PR) ,had the levels of circulating exsomal miR-451a gradually increased. While in patients who did not get remission, including stable disease (SD) and progression disease (PD) ,had no significant changes of circulating exsomal miR-451a. CONCLUSION: Circulating exsomal miR-451a may be an potential indicator for therapy response monitoring in DLBCL.

[Diagnostic Value of Protocadherin 15 for NK/T Cell Lymphoma].

OBJECTIVE: To explore whether PCDH15-SI is stable and accurate to diagnose NK/T-cell lymphoma or not. METHODS: The paraffin-biopsiy specimens were collected from 45 cases of NK/T-cell lymphoma and 33 cases of non-NK/T-cell lymphoma in Department of pathology, West China Hospital of Sichuan University. The paraffin sections were stained by immunohistochemistry and blank controls were set up. The peripheral blood was collected from these cases of NK/T-cell lymphoma and non-NK/T-cell lymphoma, as well as from the normal controls in the same hospital. The serum PCDH15 levels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Immunohistochemistry showed that PCDH15 were expressed in biopsy specimens of both the NK/T-cell lymphoma in the experimental group and the non-NK/T cell lymphoma in the control group. The expression rate in the NK/T-cell lymphoma group was higher than that in control group. The PCDH15-SI can be detected in NK/T cell lymphoma, non-NK/T cell lymphoma and the normal controls, which is higher in lymphoma patients than that in control, and the serum level was higher in the non-NK/T-cell lymphoma patients than that in the NK/T-cell lymphoma patients. Also, the serum level was higher in the patients with advanced disease than that in the patients at early stage. CONCLUSION: PCDH15 does not act as the new diagnostic marker for NK/T cell lymphoma. The serum level of PCDH15-SI may be helpful to the staging and judging therapeutic effect and prognosis for the patients with non-Hodgkin's lymphoma.

[Effects of Recombinant Human Erythropoietin on MPC-11 Myeloma Cells Cultured In Vitro].

OBJECTIVE: To explore the effect of recombinant human erythropoietin (rhEPO) on myeloma cell line MPC-11 in vitro and its anti-tumor mechamism so as to provide the theoretic evidence for treatment of multiple myeloma by using rhEPO. METHODS: MPC-11 cells were cultured in RPMI 1640 medium, then the MPC-11 cells in logarithmic growth phase were seed in 96 well culture plates at a density of 1×104/ml cells with 100 µl per well. For all the experiments, the control and rhEPO groups were set up, and the rhEPO group was divided into different concentration groups: 20, 40, 60, 80, 100, 200 and 400 rhEPO U/ml. The cultured MPC-11 cells in each groups were collected at day 1, 2, 3, 4, 5 and 6, and the viability of MPC-11 cells was assayed by using CCK-8 method, the MPC-11 cell apoptosis was detected by flow cytometry with Annexin V/PI double staining, the levels of IL-6, IgG and kappa light chain in cell supernatant were detected by ILISA. RESULTS: The apoptosis rate in MPC-11 cells treated with 200 U/ml of rhEPO at day 21 was significantly higher than that in control group(P<0.05); the apoptosis rate in MPC-11 cells treated with 400 U/ml of rhEPO at day 10, 15, 21 was higher than that in control group at same time points, respectively (P<0.05), suggesting that the MPC-11 cell apoptosis rate was enhanced with increase of rhEPO concentration and prolonging of culture time(P<0.05), the IL-6 level in supernatant of cell treated with 400 U/ml of rhEOP for 15 days was lower than that in control group(P<0.05), while the IL-6 level in supernatant of cells treated with 100, 200, 400 U/ml of rhEPO for 21 days decreased (P<0.05); The levels of IgG and kappa light chain in supernatant of cells treated with 400 U/ml of rhEPO for 21 days all were significantly lower than those in control group(P<0.05). CONCLUSION: The rhEPO can induce apoptosis of MPC-11 cells with concentration- and time-dependent manner, and can reduce levels of IgG, kappa light chain secreted by MPC-11 cells with time-dependent manner.

Assessment of Utilization and Cost-Effectiveness of Telemedicine Program in Western Regions of China: A 12-Year Study of 249 Hospitals Across 112 Cities.

BACKGROUND: The imbalance in healthcare between urban and rural areas is still a problem in China. In recent decades, China has aimed to develop telemedicine. We assessed the implementation, utilization, and cost-effectiveness of a large telemedicine program across western China. MATERIALS AND METHODS: In 2002-2013, a government-sponsored major telemedicine program was established by West China Hospital of Sichuan University (hub), covering 249 spoke hospitals in 112 cities throughout western China and in 40 medical expertise areas. We analyzed the cross-sectional data from 11,987 consultations conducted at West China Hospital using the telemedicine network over a 12-year period. The types of diseases as well as the diagnosis and treatment changes were assessed. We also performed a cost-savings analysis and a one-way sensitivity analysis. RESULTS: Of the 11,987 teleconsultations, we noted that neoplasms (19.4%), injuries (13.9%), and circulatory diseases (10.3%) were the three most common diagnoses. Teleconsultations resulted in a change of diagnosis in 4,772 (39.8%) patients, and 3,707 (77.7%) of them underwent major diagnosis changes. Moreover, it led to a change of treatment in 6,591 (55.0%) patients, including 3,677 (55.8%) changes not linked to diagnosis changes. The telemedicine network resulted in an estimated net saving of $2,364,525 (if the patients traveled to the hub) or $3,759,014 (if the specialists traveled to the spoke hospitals). CONCLUSIONS: The introduction of telemedicine in China, linking highly specialized major hospitals (hub) with hundreds of small rural hospitals (spoke), can greatly improve the quality, efficiency, and cost-effectiveness of healthcare delivery and utilization. This new Internet-based healthcare model should be utilized more widely in developing countries.

Clinical analysis of 1629 newly diagnosed malignant lymphomas in current residents of Sichuan province, China.

Previous studies in other provinces of China (Beijing, Xinjiang, Shanxi, Jiangxi, Shanghai, Guangdong, and Taiwan) suggest that the distributions of lymphoma subtypes differ compared with Western populations. In order to evaluate the characteristics of malignant lymphoma in Sichuan, China, we analyzed case series data from incident lymphoma patients diagnosed in 2008 from three hospitals, including a total of 1629 cases and including only current residents of Sichuan. The median age of diagnosis for cases was 54 years, with a higher proportion of male cases compared with female cases. The most commonly diagnosed subtypes included diffuse large B-cell lymphoma (40.4%), NK/T-cell lymphoma (NKTCL; 11.8%), mixed cellularity Hodgkin lymphoma (7.0%), mantle cell lymphoma (4.8%), and marginal zone B-cell lymphoma (3.9%). Differences in demographic characteristics between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) cases were apparent for median age at diagnosis (HL: 34 years; NHL: 57 years), and NHLs accounted for nearly all (99.3%) of the 931 cases of extranodal lymphoma. These findings indicate a higher proportion of NKTCL cases and a lower proportion of follicular lymphoma cases (2.3%) in these hospitals in Sichuan, relative to reports from some other provinces within China (e.g., Shanghai and Shanxi) and the USA. Copyright © 2015 John Wiley & Sons, Ltd.

[Clinical outcome of 489 patients with diffuse large B-cell lymphoma and associated factors].

OBJECTIVE: To investigate the clinical outcome of 489 patients with diffuse large B-cell lymphoma (DLBCL), and to identify factors associated with the clinical outcome. METHODS: Medical records of 489 DLBCL patients admitted to the West China Hospital of Sichuan University from Jan 2000 to Dec 2010 were retrospectively reviewed. The patients were divided into CHOP and RCHOP (rituximab plus CHOP) groups depending on their chemotherapy regimens. The clinical outcomes of the two groups of patients were compared. RESULTS: The RCHOP group had a higher response rate than the CHOP group (84.3% vs. 75.6%, P = 0.015). The multivariate analysis showed that splenomegaly, low absolute lymphocyte count (ALC), high IPI scores, and CHOP was associate with the low overall-response rate. In the CHOP group, low ALC (OR = 2.060, 95% CI: 1.159-3.661, P = 0.014) and high IPI scores (OR= 2. 157, 95% CI: 1.170-3.978, P = 0.014) were associate with low response rate. In the RCHOP group, anemia (OR = 3.010, 95% CI: 1.238-7.314, P = 0.015) and high IPI scores (OR = 2.872, 95% CI: 1.193-6. 914, P = 0.019) were associate with low response rate. For patients with 0.8 x 10(9)/L-1.0 x 10(9)/L ALC, RCHOP therapy was more effective than CHOP. The expression of Bcl-2 and the phenotype of immuno-classification (GCB/non-GCB) were not associated with the difference of overall response rate between the CHOP and RCHOP groups. CONCLUSION: RCHOP therapy increases the overall response rate compared with CHOP alone. Low ALC and anemia is associate with low response rate to CHOP and RCHOP therapy, respectively.

[Diagnostic value of serum levels of BamHI-W, LMP-1 and BZLF1 in NK/T-cell lymphoma].

OBJECTIVE: To explore the diagnostic value of serum levels of BamHI-W fragment, latent membrane protein-1 (LMP-1), BZLF1 and ZEBRA protein in patients with natural killer (NK)/T-cell lymphomas (NKTCLs), and to evaluate their relationship with clinical features. METHODS: A total of 144 cases were analyzed in this study, including 48 NKTCLs patients, 48 other types of non-Hodgkin's lymphomas (NHL) patients and 48 healthy individuals as controls. Fluorescent quantitative real-time polymerase chain reaction (RQ-PCR) was used to measure the copy number of BamHI-W, LMP-1 and BZLF1 in serum. Enzyme linked immunosorbent assay (ELISA) was applied to measure the serum levels of ZEBRA protein. The relative operating characteristic (ROC) curve was applied in the evaluation of the tested markers in diagnosis of NKTCL patients, and the correlations among the tested markers and clinical feature were analyzed. RESULTS: Compared with the controls, NKTCL group showed significantly higher levels of all the tested markers (P < 0.01). The median values of serum BamHI-W, LMP-1 and BZLF1 DNAs level were 1870, 394 and 499 copies/ml, respectively. And the median value of ZEBRA protein level was 73.3 µg/L. Furthermore, the ROC curves analysis revealed that all the area under curve (AUC) of LMP-1, BZLF1 and ZEBRA were more than 0.70, which were probably helpful in the diagnosis of NKTCL. To predict the presence of NKTCL, BamHI-W showed a high sensitivity of 81.3%, while BZLF1 showed a high specificity of 81.2%. Untreated patients seemed to have a significantly higher level of serum LMP1 DNA than that of treated patients (median value 898 copies/ml vs 0 copies/ml, P = 0.050). Correlation analysis showed that serum BamHI-W DNA level was correlated with the presence of B symptoms. All the three genes expressed in 94.4% of the untreated cases. On the other hand, none of them expressed in treated cases. CONCLUSIONS: It suggested that combined measurements of BamHI W, LMP1 and BZLF1 DNA levels might be helpful to the diagnosis and therapeutic monitor of NKTCL.

[The clinical characteristics of 681 patients with diffuse large B-cell lymphoma].

OBJECTIVE: To analyze clinical features and the differences of GCB and non-GCB phenotypes for diffuse large B-cell lymphoma (DLBCL) in different age groups, Ki-67 index and international prognostic index (IPI). METHODS: Clinical data of 681 patients with DLBCL hospitalized in West China Hospital from January 2000 to December 2010 were retrospectively analyzed. RESULTS: Of these DLBCL cases, the median age was 56 years old with a male predominance, 51.4% stage III-IV, 37.6% B symptoms, 30.2% IPI 3-5 scores, 49.8% from extranodal sites, 29.0% gastrointestinal tract infiltration, 38.3% low absolute lymphocyte count (ALC), 56.1% elevated serum lactate dehydrogenase (LDH) level, 83.0% elevated ß(2)-microglobulin (ß(2)-MG) level. B symptoms was associated with bone marrow involvement with the odds ratio 5.212 (95%CI 2.821 - 9.632, P = 0.000). Among 268 with DLBCL patients classified by Hans' classification, 28.4% were GCB and 71.6% non-GCB. The proportions of patients with HBsAg-positive, elevated serum LDH level and Bcl-2 positive expression in non-GCB group was higher than those in GCB group (P < 0.05). The differences between GCB and non-GCB DLBCL were not revealed in terms of age subgroups, Ki-67 expression status and IPI subgroups. The high (≥ 60%) Ki-67 group included more patients with extranodal site involvement compared with the low (< 60%) Ki-67 group (51.8% vs 38.7%, P = 0.008). The proportion of patents with low ALC in IPI 3-5 scores group was higher than in IPI 0-2 scores group (P = 0.000). The multivariate analysis showed that high IPI had statistically significant negative influence on survival (P = 0.000). CONCLUSIONS: Most patients with DLBCL were middle-aged male from our data. The patients with primary nodal (PN) was almost equal to those with primary extranodal (PEN). The most frequent extranodal site was gastrointestinal tract. The non-GCB phenotype was significantly more common than GCB phenotype in this study, and the non-GCB group included more patients with HBsAg-positive and Bcl-2 positive expression. Low ALC was observed predominantly in the high risk group. IPI score was an independent prognostic indicator for survival.

[The clinical features, therapeutic effects and prognosis of mantle cell lymphoma].

OBJECTIVE: To analyze clinical features, therapeutic effects and prognostic factors of patients with mantle cell lymphoma (MCL). METHODS: Clinical data of 37 MCL patients hospitalized in our hospital from January 2000 to March 2010 were retrospectively analyzed. RESULTS: The median age was 62, with a male predominance. 97.30% of the patients were in Ann Arbor stage III ∼ IV, 54.05% with B symptoms, 64.86% with bone marrow involvement, 29.73% with splenomegaly, 24.32% with lymphocytosis and 51.35% with elevated LDH. Ki-67 was detected in 22 cases, and patients with Ki-67 ≤ 40% accounted for 68.18%. Of 37 cases, the overall response rate (ORR) of rituximab combined with chemotherapy was 92.31%, being higher than those of CHOP (46.15%) and CHOP + IFN (42.86%) regimens. There were statistical differences in the 3-year progression-free survival (PFS) and overall survival (OS) between rituximab + chemotherapy and CHOP or CHOP + interferon regimens (P < 0.05, respectively). Splenomegaly, elevated WBC, lymphocytosis and Ki-67 > 40% were identified as adverse prognostic factors. CONCLUSION: Most patients with MCL were older adults, with a male predominance and usually had bone marrow involvement and poor prognosis. Rituximab combined with chemotherapy could improve ORR and OS of MCL.

[Establishment of a multiple myeloma local tumor model in mice].

This study was purposed to establish a multiple myeloma local tumor model in the BLAB/c mice. Healthy BLAB/c mice were injected subcutaneously with 6 x 10(5) MPC-11 cells. In the peak time of the subcutaneous nodules observed, five mice were randomized selected to be executed and the subcutaneous nodules of these mice executed were used to detect the CD138 and kappa light chain by means of HE staining and the immunohistochemistry methods. The serum immunofixation electrophoresis (IFE) of tumor-bearing mice were performed at 5, 7, 9, 11, 12, 35 and 65 days after the initial MPC-11 cell injection. Hemoglobin level was assayed at 15 and 30 days after the initial MPC-11 cell injection. The serum levels of IL-6 were also assayed at 35 and 65 days after the initial MPC-11 cell injection. The tumor volume was monitored twice a week and their body weights were measured once a week. The results showed that the peak of the subcutaneous nodules appeared at 12 to 15 days after the initial MPC-11 cell injection. The serum monoclonal immunoglobulin could be detected at 12 days after MPC-11 cell injection. The results of HE staining and immuno-histochemistry assay for detection of CD138 and kappa light chain positive expressions proved that the subcutaneous tumor nodules originated from MPC-11 plasmacytes. The serum monoclonal protein (M protein) of the tumor-bearing mice was detected at 12 days after bearing tumor which manifested thick bands of IgG and kappa light chain. The peak time of mortality was at 20 to 40 days after the initial MPC-11 cell injection, and the median survival time was 31 days. Anemia in mice appeared at 15 days. There was a significant difference of Hb level between the tumor-bearing group and the normal group at 15 and 30 days respectively (p < 0.05). The serum level of IL-6 in tumor-bearing mice was higher than that in the normal group. It is concluded that to establish the multiple myeloma local tumor model in mice by using subcutaneous injection of MPC-11 cells has various advantages, such as simple method of model established, relative high success of bearing tumor, easy observation of tumor growth change and so on. This model can be useful for studying and evaluating the therapeutic efficacy for multiple myeloma through monitoring the changes of tumor size, serum IL-6 level and serum immunofixation electrophoresis.

[Schisandrin B prevents doxorubicin-induced cardiotoxicity in rabbits].

OBJECTIVE: To study the effect of dexrazoxane in preventing doxorubicin-induced cardiotoxicity in rabbit-models and its mechanism. METHODS: Thirty one New Zealand white rabbits were randomly divided into two groups, doxorubicin (DOX) group and doxorubicin + dexrazoxane group. The cardiotoxicity was assessed by measuring serum superoxide dismutase (SOD), malondialdehyde (MDA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP), left ventricular ejection function (LVEF), and left ventricular fractional shortening (LVFS), before and 4 and 10 weeks after intervention. Pathological changes in cardiac tissues and the apoptosis of myocardial cells were examined at the end of the experiment. Results Doxorubicin increased serum MDA, cTnI and BNP and decreased SOD, LVEF and LVFS (P < 0.05). Dexrazoxane (DEX) inhibited the increase of MDA, cTnI and BNP, and the decrease of LVEF and LVFS (P < 0.05). The rabbits treated with doxorubicin + dexrazoxane had slighter pathological changes in myocardium and apoptotic myocardial cells than those treated with DOX. CONCLUSION: Dexrazoxane prevents doxorubicin-induced cardiotoxicity through decreasing oxygen free radical production, cutting down lipid peroxidation, and depressing cardiocyte apoptosis.

[Effects and mechanisms of recombinant human erythropoietin in treating multiple myeloma in murine mice].

OBJECTIVE: To test the effects and to identify appropriate dosage and possible mechanisms of recombinant human erythropoietin (rHuEPO) in treating MPC-11 myeloma in the BALB/c murine models. METHODS: A total of 420 BALB/c mice were divided into five groups. 410 of which were injected with 10(4) MPC-11 cells. The 10 mice without myeloma cell inoculation served as normal controls. On the fifth day after inoculation, 50 tumor-bearing mice were arbitrarily assigned into the placebo group, while the other 360 mice were randomly allocated into three experimental groups. Each experimental group had 120 mice and received 10, 20 and 30 units subcutaneous injection of rHuEPO, respectively. A daily injection was administered for 14 days, followed by three injections per week. The mice in the placebo group were administered with saline following the same scheme. Dynamic monitoring of serum M-protein and hemoglobin levels of the mice were performed after myeloma cell inoculation. The subcutaneous nodules were sent for pathological biopsy to ascertain the successful establishment of the murine models. The mice were randomly chosen from each group to be tested for the levels of monoclonal IgG and kappa light chain in their sera (immunofixation electrophoresis and ELISA), counts of CD4 and CD8 positive cells in whole blood (flow cytometry), microvessel density (by marking CD31) and cell apoptosis (TdT-mediated dUTP-biotin nick end labeling, TUNEL) of tumor tissues, as well as the levels of cytokines such as IL-6 and TNF-alpha in sera (ELISA) at each month after the injection of rHuEPO. RESULTS: The serum monoclonal immunoglobulin appeared on the 22nd day after inoculation of MPC-11 cells. rHuEPO increased Hb level and survival time of the mice with multiple myeloma. The serum levels of IL-6, IgG and kappa light chain decreased significantly in the mice in the treatment groups compared with those in the placebo group. The overall survival time showed a positive correlation with the Hb level (P = 0.000), and a negative correlation with the serum levels of IL-6 (P = 0.009). CONCLUSION: rHuEPO increases Hb levels and survival time and reduces serum IL-6 and M-protein of the mice with multiple myeloma.

[MMP-9 expression profile in inflammatory cells of Mip-1alpha knockout mice and Mip-1alpha receptor knockout mice].

OBJECTIVE: To explore the MMP-9 expression profile in peritoneal inflammatory macrophages and granulocytes in Mip-1alpha-, CCR1- and CCR5-deficient mice. METHODS: In sodium thioglycolate-induced murine peritonitis models, peritoneal macrophages and granulocytes were harvested, identified and purified from WT mice and Mip-1alpha-, CCR1-, CCR5-deficient mice. The RT-PCR was applied to evaluate the expression of MMP-9 in macrophages and granulocytes of different group of mice. RESULTS: The expressions of MMP-9 of macrophages in Mip-1alpha-, CCR1-, CCR5-deficient mice were significantly lower than that of WT mice (P<0.05); MMP-9 expression of granulocytes in Mip-1alpha-, CCR5-deficient mice were also significantly lower than that of WT mice (P<0.05), while the MMP-9 expression of granulocytes in CCR1-deficient mice was significant higher than that of WT mice. CONCLUSION: Deletion of Mip-1alpha and CCR5 could reduce the MMP-9 expression in both macrophages and granulocytes, while deletion of CCR1 could reduce MMP-9 expression in macrophages but increase MMP-9 expression in granulocytes.

[A clinical trial for homoharringtonine and low-dose cytosine arabinoside combined with G-CSF or GM-CSF to treat the relapsed or refractory acute myeloid leukemia (AML), geriatric AML and advanced myelodysplastic syndromes].

OBJECTIVE: To evaluate the effectiveness and toxicity of the regimen combined homoharringtonine, low-dose cytarabine with G-CSF or GM-CSF (HAG regimen) in treating patients with relapsed or refractory AML, geriatric AML and advanced myelodysplastic syndromes (MDS). METHODS: Forty patients with AML or advanced MDS were treated with HAG regimen for remission induction and consolidation therapy. All of them were followed up till April 2006. Results 20 of them (50%) achieved complete remission (CR), including 46.2% patients with relapsed or refractory AML, 60% elderly patients with primary AML who were either untreated or treated with only one course of induction therapy previously, and 66.7% patients with MDS-RAEB. After a follow-up of 6- 47 (median 23) months from the date of remission, the median times of relapse-free survival and overall survival were (7.0 +/- 1.1) and (28 +/- 12.3) months, respectively. Myelosuppression was the most significant toxicity. The incidences of infection and hemorrhage which exceed grade II were 43.8% and 37.5%, respectively. Non-hematologic adverse effects were minimal. CONCLUSION: The HAG regimen presented effective and well-tolerated. It seems promising for the treatment of relapsed or refractory AML, geriatric AML and advanced MDS.

[Acute myelomonocytic leukemia occurred after multiple myeloma treated: a case report].

We reported a case of multiple myeloma, who suffered from the acute myelomonocytic leukemia (AML-M4) after the chemotherapy of alkylating agent. The patient had a history of multiple myeloma and was treated with the regimen of including L-Sarcolysinum and cyclophosphamide for 5 years. The multiple myeloma of this patient was proved to have got the remission through bone marrow aspiration, immunofixation electrophoresis of serum, serum protein electrophoresis and detection of urine light chain. However, a pancytopenia of unknown cause was verified to peripheral blood. During the course of supportive treatment only with blood cell and platelet transfusion, WBC count of this patient showed a rising trend and the blast cells (8%-15%) started to occur in the peripheral blood. The further examination discovered that the ratio of blast cell was beyond 30% in bone marrow smear, and the flow cytometry detected the CD45, HLA-DR, CD13, CD33, CD64 to have the positive expressions. Thus, the diagnosis of multiple myeloma in remission and secondary AML-M4 was established. When the chemotherapy regimen to AML was being planned for this patient, she died of massive hemorrhage of gastrointestinal tract due to thrombocytopenia and ineffectiveness.

[Comparison of the long term results between two conditioning regimens MCC and BuCy in chronic myelocytic leukemia after allogeneic stem cell transplantation].

OBJECTIVE: To observe and evaluate the long term survival of patients with chronic myelocytic leukemia transplanted with MCC and BuCy conditioning regimens. METHODS: Fourteen cases were treated with MCC regimen (Melphanlan 170 mg/m2 x d x 1, MeCCNU 400 mg/m2 x d x 1, CTX 60 mg/kg x d x 2) and the median follow up time was 6 years; 16 cases were treated with BuCy regimen (Busulfan 4 mg/kg x d x 4, CTX 60 mg/kg x d x 2) and the median follow up time was 4 year. RESULTS: All the patients were engrafted successfully. 4 of 10 patients examined in MCC group showed mixed chimerism at day 100 after transplantation, whereas only 1 of 12 patients examined in BuCy group showed mixed chimerism. All the patients became complete donor source later without any DLI. The 5-year disease-free survival rate was 71.4% for MCC group and 62.5% for BuCy group. The transplant related mortality and relapse rate were 21% and 7% for MCC group, whereas those were 25% and 12% for BuCy group, respectively. The regimen related toxicity was relatively lower in MCC group and the median duration of hospitalization was 39 days (25-55 days) for patients with MCC regimen, and 55 days (39-90 days) for BuCy regimen. CONCLUSION: MCC regimen has a partial ablative effect on CML and the long term disease-free survival is the same as that of BuCy regimen. In regard to the cost-effect efficacy, MCC regimen has a substantial advantage over BuCy regimen.

[A paired case-control study for assessing the relationship between the incidence of malignant lymphomas and the viruses infections].

OBJECTIVE: To evaluate the relationships between the viruses infections and the incidence of malignant lymphomas (ML) in Sichuan province. METHODS: A hospital-based paired case-control study was designed with two controls per case. The case group comprised 97 cases diagnosed as ML by pathological examination; the control group A consisted of 194 subjects randomly selected from those with non-malignancies by matching on both gender and age in the corresponding period. Additionally, a control group B for Epstein-Barr virus(EBV), including 80 subjects, were chosen from other non-malignant diseases at the same time. Enzyme-linked immunosorbent assay(ELISA) was employed to test the serum antibodies and antigens of hepatitis C virus (HCV), human immunodeficiency virus (HIV), cytomegalovirus (CMV), and hepatitis B virus (HBV). The EBV was confirmed by the EBER in situ-hybridization (EBER-ISH) of pathological tissue. RESULTS: The positive rate of EBV in ML group was 70.1%(68/97) and that of control group was 7.5%(6/80). The difference between these two groups showed a statistical significance by conditional logistic regression analysis (OR = 6.58, 95% CI: 16.164-82.846, P = 0.0001). The differences in HCV, CMV and HBV infections between case group and control group demonstrated no statistical significance with P-values of 0.260, 0.258 and 0.399 respectively. We found no positive results of HIV antibody in case group and control group. CONCLUSION: The incidence of ML in Sichuan displayed a significant association with EBV infection. However, there were no relationships between the incidence of ML and the HCV, HBV, HIV, CMV infections in the area.

[Analysis of T cell subsets and CD3zeta chain expression in myelodysplastic syndrome patients].

Immune mediated suppression of hematopoiesis has been considered as one of the most important mechanisms leading to pancytopenia in myelodysplastic syndromes. This research was aimed at evaluating immune state of the MDS patients, analyzing the peripheral blood T cell subsets and CD3zeta chain expression and searching the possible reasons of hematopoietic disorders in 11 cases of MDS. Peripheral blood mononuclear cells were collected from 11 patients whose diagnosis was confirmed according to the new WHO diagnostic criteria. Flow cytometry was used for the counts of IFNgamma(+)CD4(+) cell (Th1), IL4(+)CD4(+) cell (Th2), IFNgamma(+)CD8(+) cell (Tc1), and IL4(+)CD8(+) cell (Tc2), and for the analysis of expression of CD3zeta chain in T cell subsets. The results showed that CD8(+) cells increased significantly in MDS patients; there was no significant difference between Th1/Th2, Tc1/Tc2 ratios of T cell subsets and normal control; CD3zeta chain, the functional protein in the signal transduction pathway of T cell, was over expressed in the CD8(+) cell. In conclusion, research indicates that abnormal changes of T cell subgroups exist in peripheral blood of MDS patients. Enhancement of CD8(+) cells and over-expression of CD3zeta chain are important features, which suggest that CD8(+) cells play the most critical role in the pathologic process as compared with other T cell subsets. The over active immunity mediated by T cell subset may be one of the major mechanisms resulting in cytopenia in MDS.