[Efficacy of Different Doses of Daunorubicin Induced Chemotherapy in Patients with Newly Diagnosed Primary Acute Myeloid Leukemia Under 65 Years Old].

OBJECTIVE: To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients. METHODS: The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ï¼»75 mg/(m2·d)ï¼½ and 51 cases in the standard-dose group ï¼»60 mg/(m2·d)ï¼½. And then the effects of different doses of daunorubicin on complete remission (CR) rate, minimal residual disease (MRD)-negative CR rate, relapse-free survival (RFS), overall survival (OS), and adverse events were analyzed. RESULTS: Median follow-up time of all the patients was 15 months. The CR rate and MRD- CR rate of the escalated-dose group was 88.5% and 71.4%, respectively, which were higher than 64.7% and 41.2% of the standard-dose group (P=0.029, P=0.008). The estimated 2-year RFS of the escalated-dose group was 68.4%, which was higher than 38.5% of the standard-dose group (P=0.015), but estimated 2-year OS showed no statistically significant difference (77.1% vs 66.7%, P=0.059), as well as grade 3－4 adverse events. The escalated dose of daunorubicin had prolonged RFS (13 months vs not reached, P=0.022) and OS (23 months vs not reached, P=0.029) in the FLT3-ITD－ AML patients. CONCLUSION: The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.

Intraperitoneal oxaliplatin administration inhibits the tumor immunosuppressive microenvironment in an abdominal implantation model of colon cancer.

Recent studies have demonstrated that some chemotherapeutic drugs can enhance antitumor immunity by eliminating and inactivating immunosuppressive cells. Oxaliplatin (OXP) induces immunogenic cell death by increasing the immunogenicity of cancer cells. However, the effects of OXP on the tumor immunosuppressive microenvironment remain unclear. The aim of the present study was to evaluate the antitumor activity of OXP by intraperitoneal (i.p.) administration in an abdominal implantation model of colon cancer and tested the tumor immune microenvironment to observe whether OXP affects the local immune inhibitory cell populations. Abdominal metastasis models were established by inoculation of CT26 cells. The antitumor efficacy of OXP and the tumor immune microenvironment were evaluated. The tumors and spleens of mice were harvested for flow cytometric analysis. Cluster of differentiation (CD)­8+CD69+ T cells, regulatory T cells (Tregs), CD11b+F4/80high macrophages and myeloid­derived suppressor cells (MDSCs) were evaluated by flow cytometric analysis. In vivo i.p. administration of OXP inhibited tumor growth in the abdominal metastasis model. Furthermore, OXP was observed to increase tumor­infiltrating activated CD8+ T cells in tumors, decrease CD11b+F4/80high macrophages in tumors and decrease MDSCs in the spleen. These results suggested that i.p. administration of OXP alone may inhibit tumor cell growth and induce the antitumor immunostimulatory microenvironment by eliminating immunosuppressive cells.

[Intravascular Large B-cell Lymphoma: a Clinical Analysis of 17 Cases].

OBJECTIVE: To analyze the clinical features,response to therapy and prognosis of intravascular large B-cell lymphoma (IVLBCL). METHODS: The clinical data of 17 cases with IVLBCL were retrospectively reviewed,and survival analysis was conducted. RESULTS: The study involved 10 males and 7 females of IVLBCL with a mean age of 53 years old. The most common symptom of the disease was recurrent fever (76.5%). The lymphoma was mainly observed in bone marrow (64.7%) and was clinically determined as stage ⅣB (70.6%). Many of the patients were also diagnosed with the hemophagocytic syndrome (29.4%). R-CHOP (rituximab,cyclophosphamide,epirubicin,vindesine,prednisone) or CHOP regimen chemotherapy significantly improved the survival of the patients (P=0.000 2). Unfortunately,those patients with bone marrow involvement were prone to relapse after treatment. CONCLUSION: IVLBCL is highly invasive and associated with poor prognosis. R-CHOP chemotherapy can significantly improve the prognosis.

Epidemiology and microbiology of sepsis in mainland China in the first decade of the 21st century.

OBJECTIVES: This study describes the epidemiological and microbiological profile of sepsis during the first decade of the 21(st) century in mainland China. METHODS: The sepsis-related mortality data from 2003 and 2007 were retrieved from the China Health Statistical Yearbook. The microbiology data were retrieved and selected from a literature search of the China Academic Journal Database between 2001 and 2009. A meta-analysis was performed to synthesize the available data on the proportion of positive blood cultures in septic patients and the microorganism distribution. RESULTS: The sepsis mortality in small and medium-sized cities and rural areas declined obviously over time. The mortality of the subpopulations aged 1-54 years tended to be lower than the national averages. In contrast, the sepsis mortality among neonates and the elderly (≥75 years) was obviously higher than national averages. While the mortality in the elderly declined between 2003 and 2007, the neonate sepsis mortality increased dramatically, especially among male neonates. The overall positivity of blood culture were 17.0%, 13.3% and 10.6% among neonatal, pediatric and adult patients with suspected sepsis, respectively; this proportion tended to decrease over time. Among identified microorganisms, the proportions of Gram (+) and (-) bacteria were similar (47.2% vs. 44.5%) among adult patients, while Gram (+) bacteria was predominant among neonatal (77.4%) and pediatric (73.2%) patients and increased in prevalence over time. The positivity of blood cultures and proportions of microorganisms varied by geographical region across mainland China. Sepsis with fungus was rare but was more prevalent in adult sepsis patients (6.4%) than in neonatal patients (0.8%). CONCLUSIONS: The difference in sepsis mortality between urban and rural areas decreased over time. Males, the elderly, and neonates were found to be high-risk subpopulations. Gram (+) bacteria were predominant among neonates with sepsis, but the proportion of patients with Gram (+) or Gram (-) bacteria was similar among adults with sepsis.

[Comparing BFA with BuCyA as a myeloablative conditioning regimen for allogeneic stem cell transplantation in acute leukemias].

OBJECTIVE: To compare BFA (busulfan, fludarabine plus cytarabine) with BuCyA (busulfan, cyclophoshpamide plus cytarabine) as the conditioning regimens in allogeneic stem cell transplantation for acute leukemias. METHODS: 83 patients with acute leukemia were allocated to BFA group (busulfan 3.2 mg/(kg x d), -9 d-6 d; fludarabine 30 mg/(m2 x d), -5 d(-) -1 d; cytarabine, 1 g/(m2 x d), -5 d(-) - 1 d) or BuCyA group (busulfan, 3.2 mg/(kg x d), -8 d(-) - 5 d; cyclophoshpamide 60 mg/(kg x d),-2 d(-) - 1 d; cytarabine, 3 g/(m2 x d), -4 d(-) - 3 d). Their three-year disease-free survival (DFS) rate, complete remission (CR) rate and incidences of acute graft versus host disease (aGVHD) and hemorrhagic cystitis were monitored. RESULTS: BuCyA group had lower DFS (40.0% vs 61.9%, P = 0.039 9) and lower CR (44.0% vs 71.6%, P = 0.031 0) than BFA group. About 20% of patients treated with BuCyA were not in remission, compared with 51.6% of those treated with BFA. aGVHD occurred in 46.7% patients in the BuCyA group and 50.9% patients in the BFA group, which were 23.3% and 9.4%, respectively, for those graded III - IV. Severe infection occurred in 23.3% patients in the BuCyA group and 22.9% patients in the BFA group. Severe bleeding occurred in 26.7% patients in the BuCyA group and 11.4% patients in the BFA group. The incidence of hemorrhagic cystitis in the BuCyA group and BFA group was 16.7% and 5.7%, respectively. CONCLUSION: BFA is a safer and more effective conditioning regimen compared with BuCyA.

Chemo-immunotherapy with oxaliplatin and interleukin-7 inhibits colon cancer metastasis in mice.

Combination of immunotherapy and chemotherapy has shown promise for cancer. Interleukin-7 (IL-7) can potentially enhance immune responses against tumor, while oxaliplatin (OXP), a platinum-based drug, can promote a favorable immune microenvironment and stimulate anticancer immune responses. We evaluated the anti-tumor activity of IL-7 combining OXP against a murine colon carcinoma in vitro and in vivo and studied the tumor immune microenvironment to investigate whether the combined treatment affects on the local immune cell populations. Utilizing lung and abdomen metastasis models by inoculation of CT26 mice colon cancer cells, we evaluated the anti-tumor efficacy of combining IL-7 and OXP in mice models. Tumor immune microenvironment was evaluated by flow cytometric analysis and immunohistochemical staining. Our study showed that the in vivo administration of IL-7 combined with OXP markedly inhibited the growth of tumors in lung and abdomen metastasis models of colon cancer. IL-7 alone had no effect on tumor growth in mice and IL-7 did not alter cell sensitivity to OXP in culture. The antitumor effect of combining IL-7 and OXP correlated with a marked increase in the number of tumor-infiltrating activated CD8+ T cells and a marked decrease in the number of regulatory T (Treg) cells in spleen. Our data suggest that OXP plus IL-7 treatment inhibits tumor cell growth by immunoregulation rather than direct cytotoxicity. Our findings justify further evaluation of combining IL-7 and chemotherapy as a novel experimental cancer therapy.

Efficacy and safety of leflunomide for the treatment of BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients.

BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation. So far, no specific antiviral drug with proven efficacy has been approved for treating BKV-HC. Leflunomide is an immunosuppressive drug with antiviral activity and has been used in treating BKV-associated nephropathy after renal transplantation. This is the first report on the efficacy and safety of leflunomide in the treatment of BKV-HC. From January 2006 to January 2009, 89 patients received allogeneic hematopoietic stem cell transplantation, and among them, 18 patients were identified as having BKV-HC, with a 20% cumulative incidence. Fourteen patients were treated with oral leflunomide. Three days of 100 mg/day leflunomide was used as loading doses and followed by maintenance doses of 20 mg/day. The urinary BKV-DNA load was monitored weekly by real-time quantitative PCR. The efficacy was evaluated on day 20 after leflunomide treatment. Seven patients (50%) achieved complete remission, 5 patients (35.7%) achieved partial remission, and 2 patients (14.3%) had more than a 1-log reduction in urinary BKV-DNA loads after treatment. During the leflunomide treatment, the graft-versus-host disease of the patients did not progress, and the dosages of the immunosuppressant were reduced simultaneously. One patient discontinued treatment because of intolerable gastrointestinal symptoms. Neutropenia occurred in 2 cases. These preliminary data suggest that leflunomide may be a potentially effective medication for treating BKV-HC without significant toxicity, but evidence supporting its use requires randomized controlled trials.

Clinical prognostic analysis of 116 patients with primary intestinal non-Hodgkin lymphoma.

The gastrointestinal tract is the most common extranodal invasion site of non-Hodgkin lymphoma (NHL). Primary gastrointestinal NHL is often discussed together in most survival analyses. Primary intestinal NHL is significantly different from primary gastric NHL with regard to clinical features, pathological subtype, treatment, and prognosis. In this article, we analyzed clinical and pathological characteristics of primary intestinal NHL, and we also explored prognostic factors for primary intestinal NHL. A retrospective analysis was carried out on clinical data from 116 cases of confirmed primary intestinal NHL. The Kaplan-Meier method was used for the survival analysis. A Cox model was used for a multivariate analysis. In 116 patients with primary intestinal NHL, 79 patients were men (68.1%) and 37 patients were women (31.9%). In the cases used in this study, 68 were B-cell NHL and 48 were T-cell NHL. The age, incidence of intestinal obstruction, B symptom and performance status (PS) were closely related with pathological subtype. One-year and two-year survival rates were 76.7 and 58.3%, respectively. The log-rank univariate analysis showed male patients, PS score greater than or equal to two, hypoproteinemia, intestinal perforation, T-cell type, late stage (III/IV), no radical surgery, and no chemotherapy had relatively poor prognoses. Cox multivariate analysis shown that gender (95.0% CI 0.218-0.721), pathological subtype (95.0% CI 1.484-4.179), and radical surgery (95.0% CI 0.110-0.394) were independent prognostic risk factor for primary intestinal NHL. Male patients, T-cell intestinal lymphoma, and no radical surgery had rapid clinical processes and poor prognoses.

Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications.

BACKGROUND: Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by up-regulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. However, the impact of COX-2 on lymphangiogenesis of gastric cancer remains unclear. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis. METHODS: Using immunohistochemistry, COX-2, VEGF-C and level of LVD were analyzed in 56 R0-resected primary gastric adenocarcinomas, while paracancerous normal mucosal tissues were also collected as control from 25 concurrent patients. The relationships among COX-2 and VEGF-C expression, LVD, and clinicopathologic parameters were analyzed. The correlations of COX-2, VEGF-C and level of LVD with patient prognosis were also evaluated by univariate tests and multivariate Cox regression. RESULTS: The expression rates of COX-2 and VEGF-C were 69.64% and 55.36%, respectively, in gastric carcinoma. Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (P < 0.05). It was significantly correlated with lymph node metastasis and invasion depth (P = 0.003, P = 0.05). VEGF-C was significantly associated with peritumoral LVD (r = 0.308, P = 0.021). However, COX-2 was not correlated with VEGF-C (r = 0.110, P = 0.419) or LVD (r = 0.042, P = 0.758). Univariate analysis showed that survival time was impaired by higher COX-2 expression and higher peritumoral LVD. Multivariate survival analysis showed that age, COX-2 expression and peritumoral LVD were independent prognostic factors. CONCLUSIONS: Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD. Our data did not show that overexpression of COX-2 promotes tumor lymphangiogenesis through an up-regulation of VEGF-C expression in gastric carcinoma. Age, COX-2 and peritumoral LVD were independent prognostic factors for human gastric carcinoma.

[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.