Juying Wei

Epigenetic priming with decitabine followed by low-dose idarubicin/cytarabine has an increased anti-leukemic effect compared to traditional chemotherapy in high-risk myeloid neoplasms

Abstract Decitabine (DAC) is commonly used for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Previous studies have indicated DAC sequentially combined with idarubicin was an effective treatment for myeloid neoplasms. Therefore, a clinical study was conducted of the sequential combination of DAC followed by low-dose idarubicin/cytarabine in high-risk myeloid neoplasms. A total of 30 patients with a diagnosis of high-risk MDS, AML evolving from MDS or relapsed/refractory AML were enrolled in the study. DAC was administered 20 mg/m2 daily for 3 consecutive days. Idarubicin (3 mg/m2/day) was administered 24 h after the last administration of DAC for 5–7 consecutive days, combined with cytarabine (30 mg/m2/day) for 7–14 days. The overall complete remission rate was 66.67%. The results demonstrate that epigenetic priming with decitabine followed by low-dose idarubicin/ytarabine has an increased anti-leukemia effect compared to traditional chemotherapy in high-risk myeloid neoplasms.

Novel influenza A (H1N1) in patients with hematologic disease

Patients with hematologic disease are likely to be at increased risk for infection with influenza. We retrospectively analyzed 11 cases of patients with hematologic disease who were infected with pandemic H1N1 virus in our department, including their clinical manifestations, laboratory and imaging findings, outcomes of antiviral therapy, and factors associated with mortality. Notably, nine patients had lower respiratory tract disease. Five patients progressed to respiratory failure and eventually died, despite treatment with antivirals and/or corticosteroids and/or mechanical ventilation. We concluded that H1N1 2009 infection was associated with a severe course and high rate of mortality in patients with hematologic disease, and early diagnosis and antiviral treatment were important to reduce the rate of severe complications and mortality.

PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation

Patients with secondary acute myeloid leukemia (sAML) arising from myelodysplastic syndromes have a poor prognosis marked by an increased resistance to chemotherapy. An urgent need exists for adjuvant treatments that can enhance or replace current therapeutic options. Here we show the potential of LB100, a small-molecule protein phosphatase 2 A (PP2A) inhibitor, as a monotherapy and chemosensitizing agent for sAML using an in-vitro and in-vivo approach. We demonstrate that LB100 decreases cell viability through caspase activation and G2/M cell-cycle arrest. LB100 enhances daunorubicin (DNR) cytotoxicity resulting in decreased xenograft volumes and improved overall survival. LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3′ untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. Our research highlights the therapeutic potential of LB100, and provides new insights into the mechanism of LB100 chemosensitization.

Diagnosis and management of acquired thrombotic thrombocytopenic purpura in southeast China: a single center experience of 60 cases

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected in 10 years in a single center in southeast China. A total of 60 patients diagnosed with acute acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients, 52 patients presented with their first episodes, and eight patients had two or more episodes. The median age at presentation was 49 (range, 17 to 78) years with a female predominance (male:female ratio, 1:1.60). ADAMTS 13 activity were analyzed in 43 patients, among whom 33 (76.7%) patients had a baseline level of < 5%. Mortality was 30%. Plasma exchange (PEX) was performed in 62 of 69 (89.9%) episodes. Corticosteroids were administered in 54 of 69 (78.3%) episodes. Other immunosuppressants (e.g., vincristine, cyclosporine, and cyclosporin) were used in 7 of 69 (10.1%) episodes. Rituximab was documented in 4 patients with refractory/relapsed TTP for 5 episodes, showing encouraging results. In conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the mainstay of the therapy, and rituximab can be used in relapsed/refractory disease.

Impact of Chemotherapy Delay on Overall Survival for AML with IDH1/2 Mutations: A Study in Adult Chinese Patients.

The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.

Primary central nervous system lymphoma: Retrospective analysis of 34 cases in a single centre:

Objective To retrospectively analyse outcomes in patients with primary central nervous system lymphoma (PCNSL), which is a malignant CNS non-Hodgkin’s lymphoma with a poor prognosis. Methods This study retrospectively analysed the treatment and outcomes of patients with PCNSL, which were divided into two groups: surgery (S) group and surgery/biopsy+chemotherapy (SC) group. The latter group was further subdivided into four cohorts based on the treatment regimen: cyclophosphamide, epidoxorubicin, vincristine and prednisone (CHOP), high-dose methotrexate (HDM)+dexamethasone+rituximab (HDM+D+R), HDM+D+temozolomide (HDM+D+T), and HDM+D+R+T. Results The study enrolled 34 patients; 10 of which received surgery only. Between the S and SC groups, the median progression-free survival (PFS) and overall survival (OS) of intracranial PCNSLs (n = 32) were 8.5 months versus 29 months, respectively; and 8.5 months versus 54 months, respectively (5-year OS: 10.0% versus 48.7%, respectively; 2-year PFS: 0.0% versus 52.6%, respectively). Comparing the CHOP and HDM-based chemotherapy cohorts, the median PFS and OS were 15 months versus not achieved, respectively, and 25 months versus not achieved, respectively (5-year OS: 20.0% versus 60.8%, respectively; 2-year PFS: 20.0% versus 62.7%, respectively). Conclusion Chemotherapy appears to provide a better OS and PFS for patients with PCNSLs compared with surgery alone. HDM+D+T and HDM+D+R+T may be effective choices for PCNSL treatment.

The crosstalk between autophagic and endo-/exosomal pathways in antigen processing for MHC presentation in anticancer T cell immune responses

T cells recognize antigen fragments from proteolytic products that are presented to them in the form of peptides on major histocompatibility complex (MHC) molecules, which is crucial for the T cell to identify infected or transformed cells. Autophagy, a process that delivers cytoplasmic constituents for lysosomal degradation, has been observed to provide a substantial source of intra- and extracellular antigens for MHC presentation to T cells, which will impact the tumor-specific immune response. Meanwhile, extracellular components are transported to cytoplasm for the degradation/secretion process by the endo-/exosomal pathway and are thus involved in multiple physiological and pathological processes, including immune responses. Autophagy and endo-/exosomal pathways are intertwined in a highly intricate manner and both are closely involved in antigen processing for MHC presentation; thus, we propose that they may coordinate in antigen processing and presentation in anticancer T cell immune responses. In this article, we discuss the molecular and functional crosstalk between autophagy and endo-/exosomal pathways and their contributions to antigen processing for MHC presentation in anticancer T cell immune responses.

Autophagy regulation and its dual role in blood cancers: A novel target for therapeutic development (Review)

Autophagy, a physiological process in which cellular components are degraded by the lysosome for cell homeostasis, plays an important role in cell metabolism, including cell proliferation, differentiation, survival and apoptosis. Recent studies indicate that autophagy serves as a survival mechanism by eliminating misfolded proteins and attenuating DNA damage. Autophagy can also suppress tumor growth, depending upon the cell context and functional status. Dysfunction of autophagy may be closely linked to the initiation and development of various diseases, including hematological malignancies. Mounting evidence highlights the dual role of autophagy in blood cancers through multifarious signal pathways. Therefore, strategies targeting autophagy will develop innovative therapeutic approaches for blood cancers, improve the efficacy of chemotherapy, and bring significant benefits for patients.

Clinical and biological characteristics of acute myeloid leukemia with 20–29% blasts: a retrospective single-center study

Abstract It is controversial whether acute myeloid leukemia (AML) patients with 20–29% bone marrow (BM) blasts should be considered AML or myelodysplastic syndromes (MDS). We retrospectively studied 382 patients, including 108 AML with 20–29% BM blasts (AML20–29), 210 AML with ≥30% BM blasts (AML ≥ 30), and 64 MDS with 10–19% BM blasts (MDS-EB2). We found that AML20–29 were more similar to MDS-EB2 in terms of advanced age, less blood count, the increased presence of poor-risk cytogenetics. The frequency of mutated genes in AML20–29 had both the characters of AML and MDS. Median overall survival of AML20–29 and MDS-EB2 were similar and shorter than those of AML ≥ 30 (p = .045). Multivariate analysis showed inferior survival with increased age, low platelet count and FLT3 mutations. Our findings suggest that AML20–29 have clinical features more similar to MDS than AML.

Publisher Correction: PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.