Venetoclax combined with decitabine induced tumor lysis syndrome in a young patient with acute myeloid leukemia: a case report and literature review.

Venetoclax, in combination with hypomethylation agents (HMAs), is a novel treatment for leukemia patients with low chemotherapy tolerance. However, it has been reported to be a risk of causing tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL) and elderly acute myeloid leukemia (AML) patients. Here we report a rare case of a young adult AML patient who induced TLS after receiving a combination therapy of venetoclax with decitabine (DEC). A 36-year-old male patient presented with an unexplained fever and was diagnosed with AML-M5a. The patient was first treated with a combination of antibiotics, including voriconazole 300 mg Q12h. After the infection was relieved, he was treated with 100 mg venetoclax in combination with 75 mg/m 2 DEC. However, 12 h after the first treatment, he developed diarrhea, fatigue and other symptoms, and the laboratory results were consistent with the laboratory TLS. The patient stopped chemotherapy immediately, and TLS gradually improved after receiving rehydration, diuresis, dialysis and other treatments. Finally, the patient achieved complete remission. Based on the experience of this case and related studies, we recommend the prevention of TLS should not be limited to elderly patients taking venetoclax, and it is equally important in young patients. And reduce the dosage of venetoclax when using azole antifungal drugs.

Acute Promyelocytic Leukemia Presenting With a Myeloid Sarcoma of the Spine: A Case Report and Literature Review.

Myeloid sarcoma is a rare extramedullary tumor of immature myeloid cells. Certain known acute myeloid leukemia cytogenetic abnormalities, in particular t(8,21), has been associated with a higher incidence. Myeloid sarcoma, which rarely happens in acute promyelocytic leukemias, is more common in recurrent patients after the advent of all-trans retinoic acid (ATRA) and are rare in untreated acute promyelocytic leukemia. We described a case of, to our knowledge, de novo myeloid sarcoma of the spine confirmed as acute promyelocytic leukemia. Myeloid sarcoma is diagnosed by spinal tumor biopsy, and microscopic examination of a bone marrow smear and cytogenetic analysis led to a confirmed diagnosis of acute promyelocytic leukemia.

Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population.

Plasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian populations, but the relationship is not yet documented in Han Chinese in population-based study. Therefore, we undertook a case-control study of this relationship among patients with venous thromboembolism, and probed the genetic factors contributing to low protein S deficiency. Among the 603 consecutively recruited venous thromboembolism patients, 51 (8.5%) proved to be deficient in free protein S antigen (lower than 38.6 U/dl), among whom 30 cases were identified to have a causative mutation by direct sequencing. In contrast, six cases (1.0%) of the 584 healthy controls had low free antigen levels, among whom direct sequencing confirmed disease-causing gene mutations in four controls (0.7%). After adjusting for age and gender, the odds ratio of developing venous thromboembolism in individuals with protein S deficiency based on free protein S tests was 8.1 (95% CI = 3.6-19.9, P < 0.001). Gene sequencing yielded 24 different heterozygous mutations in the 34 participants, of which 13 were newly described. 17 (50%) of the 34 mutations in our study cohort occurred in exons 12 and 13, indicating the LGR2 domain to be a hotspot mutation region for the protein. These findings are conducive to the clinical application of protein S assays for the molecular diagnosis of thrombophilia.

A 3-miRNA signature predicts prognosis of pediatric and adolescent cytogenetically normal acute myeloid leukemia.

Acute myeloid leukemia is a hematologic malignancy with significant molecular heterogeneity. MicroRNAs have important biological functions and play critical roles in pathogenesis and prognosis in a variety of cancers including acute myeloid leukemia. Some reports have constructed risk stratification systems for adult acute myeloid leukemia patients using microRNAs to predict an optimal outcome of patients. However, little has been done in pediatric and adolescent patients. The purpose of this study is to identify a panel of microRNA signature that could predict prognosis in younger cytogenetically normal acute myeloid leukemia patients by analyzing the data from The Cancer Genome Atlas. A total of 59 cytogenetically normal acute myeloid leukemia patients under 21 years with corresponding clinical data were enrolled in our study. Using univariate Cox's model, we found 17 miRNAs were significantly related with overall survival in pediatric and adolescent cytogenetically normal acute myeloid leukemia patients but no clinical parameter was found significant related with overall survival. The multivariate Cox regression identified high expression of hsa-miR-146b was independent poor prognostic factor and high expression of hsa-miR-181c and hsa-miR-4786 appeared to be favorable factors. A model was proposed based on these three miRNAs. Leave-one-out Cross Validation method and Permutation Test was further used to evaluate this model. The function role of has-mir-181c was further studied by carrying out flow cytometry and cell counting kit-8 (CCK-8) in U937 cell line. The results indicate that the 3-microRNA-based signature is a reliable prognostic biomarker for pediatric and adolescent cytogenetically normal acute myeloid leukemia patients.

Air pollution and venous thrombosis: a meta-analysis.

Exposure to air pollution has been linked to cardiovascular and respiratory disorders. However, the effect of air pollution on venous thrombotic disorders is uncertain. We performed a meta-analysis to assess the association between air pollution and venous thrombosis. PubMed, Embase, EBM Reviews, Healthstar, Global Health, Nursing Database, and Web of Science were searched for citations on air pollutants (carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and particulate matters) and venous thrombosis. Using a random-effects model, overall risk estimates were derived for each increment of 10 µg/m(3) of pollutant concentration. Of the 485 in-depth reviewed studies, 8 citations, involving approximately 700,000 events, fulfilled the inclusion criteria. All the main air pollutants analyzed were not associated with an increased risk of venous thrombosis (OR = 1.005, 95% CI = 0.998-1.012 for PM2.5; OR = 0.995, 95% CI = 0.984-1.007 for PM10; OR = 1.006, 95% CI = 0.994-1.019 for NO2). Based on exposure period and thrombosis location, additional subgroup analyses provided results comparable with those of the overall analyses. There was no evidence of publication bias. Therefore, this meta analysis does not suggest the possible role of air pollution as risk factor for venous thrombosis in general population.

Efficacy and Safety of Panobinostat in Relapsed or/and Refractory Multiple Myeloma: Meta Analyses of Clinical Trials and Systematic Review.

During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer relapsing. Thus, novel therapeutic agents are needed. We aimed to assess the efficacy and safety of a novel agent panobinostat for patients with relapsed or/and refractory MM. A systematic literature review identified studies for clinical trials about panobinostat in patients with relapsed or/and refractory MM. We searched studies published between January 2000 and December 2015 in Pubmed, Ovid, EBSCO and the Cochrane library. Random-effect pooled estimates were calculated for overall response rate and rates of common adverse effects. The results showed 11 clinical trials including 700 patients with relapsed or/and refractory MM treated with panobinostat were identified. The ORR varied between 0.08 and 0.67. Pooled analyses showed the results that the ORR was 0.45 (95% CI: 0.31-0.59, I(2) = 90.5%, P = 0.000) for panobinostat combined with any other kind of drugs. The most common Grade3/4 adverse effects were thrombocytopenia, neutropenia, lymphopenia, anemia, diarrhea, fatigue, nausea and so on. In conclusion, based on our analyses, the regimen of panobinostat combining with other agents seems to be well tolerated and efficacious in patients with relapsed or/and refractory MM.

Protective effects of neferine on amiodarone-induced pulmonary fibrosis in mice.

The effects of neferine, a bisbenzylisoquinline alkaloid extracted from the Chinese traditional medicine seed embryo of Nelumbo nucifera Gaertn, on amiodarone-induced pulmonary fibrosis in mice were evaluated. Adult Kunming mice were induced to develop pulmonary fibrosis through intratracheal instillation of amiodarone (6.25 mg/kg) on the 1st, 3rd and 5th day. Mice were treated orally with saline, neferine (20 mg/kg), prednisolone (15 mg/kg), pirfenidone (100 mg/kg) twice a day after the third amiodarone instillation. On Day 21, all the lung tissues were collected for hydroxyproline measurement and the histological examination by hematoxylin-eosin and Masson staining. All the blood sample were collected for surfactant protein-D (SP-D) levels assay, Th1/Th2 balance valuation, CD4+CD25+ regulatory T cells (Tregs) analysis by Enzyme-linked immunosorbent assay and flow cytometry. Our data showed that neferine significantly restored the significant reductions in body weights, the increased levels of lung index and hydroxyproline, the abnormal histological findings, the serum SP-D increase, the Th1/Th2 imbalance by decreasing IL-4 and increasing IFN-γ levels and the increases in the population of CD4+CD25+ Tregs associated with amiodarone instillation in mice. Similar changes were also observed in the prednisolone or pirfenidone treated mice. In conclusion, these results indicated that neferine possessed a significant inhibitory effect on amiodarone-induced pulmonary fibrosis, probably due to its properties of anti-inflammation, SP-D inhibition and restoring increased CD4+CD25+ Tregs which may modulate Th1/Th2 imbalance by suppressing Th2 response (from Th2 polarity toward a Th1 dominant response).