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Splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL) are rare indolent chronic B-cell lymphomas. Clinical research has made a great progress thanks to the developments of genomic studies and a large number of overlapping mutational profiles involving NOTCH, BCR and nuclear factor κB (NF-κB) signaling, chromatin remodeling, and the cytoskeleton. This paper reviews the recent progress of biological characteristics and treatment progress of SMZL and NMZL in indolent lymphoma combined with the 59th American Society of Hematology (ASH) Annual Meeting.
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Waldenström macroglobulinemia (WM) is a rare lymphoma without a curable treatment method, which is characterized by MYD88 and CXCR4 gene mutations. The study on clinical manifestations, the pathological and genomic features has led to a series of promising clinical protocols. This article reviews the safety and efficacy of drugs including alkylating agents, proteasome inhibitors, monoclonal antibodies, and Bruton tyrosine kinase (BTK) inhibitors in WM patients combined with the latest research of the individualized treatment for WM at the 59th American Society of Hematology (ASH) Annual Meeting, so as to analyze the feasibility of basic genomic treatment and current integrated regimens for WM.
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Objective@#To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai.@*Methods@#A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data.@*Results@#A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance.@*Conclusions@#The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.
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Myeloma is a malignancy associated with significant immune dysfunction imparted by both the disease itself as well as many of the immunosuppressive therapies that have been used in the past.The growing body of preclinical data regarding immunoregulatory mechanisms that appear active in myeloma has begun to be translated to clinical trials targeting these signalling axes.This review summarized the current understanding of the basic biology of several immune checkpoint pathways that may be important in myeloma and provide an up-to-date overview of recent and ongoing clinical trials of immune checkpoint inhibitors in myeloma.Finally,several current challenges and possible future direction of immune checkpoint blockade in myeloma will be reviewed.
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Allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survival,but limited efficacy and associated toxicities have prevented its widespread application.Cellular immunotherapies and vaccines are explored to induce more specific,reliable,and potent antimyeloma immune responses with less treatmentrelated risk.Advances in molecular biology,basic and applied immunology,have led to several promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes,vaccine primed ex vivo expanded autologous T cells,expanded marrowinfiltrating lymphocytes,and plasma cell/dendritic cell fusion vaccines.The combination of these emerging therapies to immunomodulatory drugs and inhibitors of programmed death-1 T-cell regulatory pathways could improve the outcome for MM patients.This article reviews the latest progress of cellular and vaccine immunotherapy for MM at the 58th American Society of Hematology (ASH) Annual Meeting,and discusses how these therapies might integrate and synergize with existing treatment paradigms.
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Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the Western world,and is potentially curable with standard R-CHOP chemoimmunotherapy. We are now in an era that the heterogeneity of DLBCL is defined genetically and molecularly,and rational subset-specific therapeutic targets are guiding clinical trials.Primary mediastinal DLBCL is a unique clinicopathologic entity, and alternatives to R-CHOP may confer superior outcome. Rearrangement of the myc oncogene occurs in 10%of patients with DLBCL, and confers a very poor prognosis with standard R-CHOP, particularly when there is concomitant rearrangement of bcl-2, a condition referred to as double-hit DLBCL. A larger subset of DLBCL demonstrates overexpression of both myc and bcl-2 by immunohistochemistry. Analyze the source of cells by gene expression profile, immunohistochemistry algorithms,or a novel Lymph2Cx platform,provides prognostic information, and guides therapeutic decisions in both relapsed and de novo disease. This article reviews latest research presented at the 57th American Society of Hematology (ASH) annual meeting on the definition of specific subsets of DLBCL and selection of subtype-specific treatment,including novel approaches under investigation. Understanding these key features of the pathology report, and limitations of these assays defining subsets of DLBCL, allows for a precision medicine approach to this disease.
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Despite many recent advances in the treatment of multiple myeloma (MM), the course of the disease is characterized by a repeating pattern of periods of remission and relapse as patients cycle through the available treatment options. Evidence is mounting that long-term maintenance therapy may help suppressing residual disease after definitive therapy, prolonging remission and delaying relapse. For patients undergoing autologous stem cell transplantation (ASCT), lenalidomide maintenance therapy has been shown to improve progression-free survival (PFS), however, it is still unclear whether this translates into extended overall survival (OS). For patients ineligible for ASCT, continuous therapy with lenalidomide and low-dose dexamethasone is shown to improve PFS and OS (interim analysis) compared with a standard, fixed-duration regimen of melphalan, prednisone, and thalidomide in a large phase Ⅲ trial. Other trials have also investigated thalidomide and bortezomib maintenance for ASCT patients, and both agents have been evaluated as continuous therapy for those who are ASCT ineligible. However, some important questions regarding the optimal regimen and duration of therapy must be answered by prospective clinical trials before maintenance therapy, and continuous therapy should be considered routine practice. This article reviewed the available data on the use of maintenance or continuous therapy strategies and highlights ongoing trials reported in the 57th American Society of Hematology (ASH) annual meeting that would help to further define the role of these strategies in the management of patients with newly diagnosed MM.
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Mantle cell lymphoma (MCL) is a group of highly aggressive non-Hodgkin lymphoma (NHL) in small B-cell lymphoma, accounting for 6 % of NHL incidence. MCL is characterized with its concealed onset, strong aggression, high malignancy and poor prognosis. Therefore, more attention should be paid to the diagnosis and differential diagnosis of MCL in clinic. Recently, diagnostic models of molecular pathology, researches on cyclin D1 protein negative MCL, staging prognosis and stratification treatment of MCL are worthy of attention.
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In this last decade,one of the major advances in the management of multiple myeloma has been the introduction of the novel agents thalidomide,bortezomib,and lenalidomide as part of treatment in young patients eligible for high-dose therapy (HDT) and autologous stem cell transplantation (ASCT).These drugs have markedly improved the rate of complete remission both before and after ASCT without substantially increasingly toxicity.The implementation of an ‘optimal strategy’ consisting of novel-agent-based induction,HDT,and the use of novel agents in consolidation and maintenance may result in 5-year survival rate of 80 ％ and cure might be considered in a subset of patients who present with good prognostic features at the time of diagnosis.Nevertheless,the high efficacy of the novel agents has led some groups to test these agents upfront without ASCT.At the end of 2014,preliminary randomized data favor early ASCT plus novel agents over novel agents alone.Therefore,the optimal approach to the treatment of multiple myeloma is still to propose the most effective treatment that should involve the use of frontline ASCT in young patients eligible for HDT.This article reviews the latest research presented at the 56th American Society of Hematology (ASH) annual meeting on the multiple myeloma and its clinical management.
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Outcomes for patients with hemophilia have improved dramatically over the past 50 years.With the increased availability of safe clotting factor concentrates,the primary focus in clinical management is now the prevention of long-term complications,most notably the debilitating hemophilic arthropathy that is associated with severe disease.Definitive evidence of improved clinical results from primary prophylaxis started in young patients-with severe hemophilia A and a minimal bleeding history is presented.Furthermore,recent studies showing benefits for initiating prophylaxis in older adolescents and adults with established joint disease are examined.lnhibitors to factor Ⅷ are the most problematic complication of factor replacement therapy.Patient-specific and treatment-related factors that contribute to the risk of inhibitor formation are discussed and controversies and clinical evidence related to approaches for tolerance induction are reviewed.Immune tolerance induction is the proven method for eradication of inhibitors.This article reviews latest research presented at the 55th ASH annual meeting on the hemophilias and their clinical management.
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Multiple myeloma (MM) is a plasma cell malignancy. With the development of the understanding of MM, the diagnosis is no more limited to bone marrow biopsy and imageological examination. Serum free light chain, cytogenetic analysis and molecular biology study are becoming increasingly widely used, which give us a deeper under-standing of the mechanisms of MM and provide us with a clearer prognosis evaluation. Here is to make a review of the diagnosis and its development of MM from laboratory examination, diagnosis criteria and classiifcation.
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Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion ofbone marrow plasmacytes.It accounts for 10 ％ of all hematological malignancies.The proteasome,an intracellular enzyme complex that degrades ubiquitin-tagged proteins to regulate protein levels within the cell,plays an important role in maintaining cellular homeostasis.Proteasome inhibitors proved to be significantly effective in the clinical treatment of MM.In recent years,the application of the proteasome inhibitor has led to increased survival rates in MM patients.Bortezomib is the first proteasome inhibitor that has been approved by the US Food and Drug Administration due to its ability to reversibly inhibit the 26 s proteasome functions.Despite the fact that Bortezomib improves medical treatment,many patients experience difficulty responding to this drug and some patients who do respond eventually relapse.These results have led researchers to investigate new proteasome inhibitors with mechanisms different from those of Bortezomib.Some drugs that bind to the active site of the proteasome and irreversibly inhibit the complex have recently been developed and are currently being tested in advanced clinical trials.Here,we will elaborate on the proteasome inhibitors targeting MM and focus on newly discovered inhibitors that may overcome the resistance to Bortezomib.
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Objective To investigate the effect of valproic acid (VPA) on NKG2D-ligand expression in ARK,OPM2 human myeloma cell lines and their sensitization to natural killer (NK) cell-mediated Killing.Methods Different concentrations of VPA from 0-5.0 mmol/L were used to treat ARK,OPM2 cells respectively,then the cell viabilities were tested by flow cytometry (FCM).Real-time quantitative-PCR and FCM were used to detect the changes in mRNA,protein levels of NKG2D-ligand respectively in the two cell lines treated with 1 mmol/L VPA for 48 hours.The calcein-release-assay (CARE-LASS) was carried out to detect cytotoxic changes of NK cells against mydoma cells after VPA treatment.Results VPA induced the expression of MICA/B,ULBP2 (P ＜ 0.05) and in turn enhanced the NK cytotoxicity on myeloma cells.The enhancing effect of VPA was blocked by NK cells pretreated with anti-NKG2D mAb (P ＜ 0.05).The primary mechanism of NK cell killing of myeloma cells was perforin/granzyme-mediated.Conclusion VPA can induce the expression of MICA/B,ULBP2 in ARK,OPM2 cells,thereby enhancing the cytotoxicity against myeloma cells,which implies a new mechanism of anticancer approach and may be a new approach in myeloma immunotherapy.
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Chelation therapy could remove transfusional iron burden. Three chelators are currently available, including deferoxamine, deferiprone, and deferasirox, which can be used as monotherapy or in combination.Several factors must be considered in the design of optimal and individualized chelation regimens,which include chelator availability and its properties,degree of organ-specific iron loading,ongoing transfusional iron burden, and patient preference. Comparative effectiveness trials may help to determine the ideal strategy. This article reviews latest research presented at the 53rd annual meeting of the American Society of Hematology (ASH) on the use of iron chelators.
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<p><b>OBJECTIVE</b>To study the pathological and clinical characteristics of a patient with spontaneous platelet aggregation of his giant and morphologically abnormal platelets.</p><p><b>METHODS</b>Platelet size and structure were observed under light microscope and electron microscope. Platelet aggregation was measured turbidometrically. Platelet glycoproteins (GP) were analyzed using flow cytometry. PCR and DNA sequencing were performed to identify the gene abnormality.</p><p><b>RESULTS</b>The patient had spontaneous platelet aggregation of giant platelets with thickened plasma membrane and increased number of granules in various shapes. Aspirin and ticlopidine did not affect the spontaneous aggregation. The expression of GP I b, GP II b, GP III a and P-selectin in the platelet membrane were in normal range. Results of gene analyses for GP I balpha, GP I bbeta and GPIX were also normal.</p><p><b>CONCLUSION</b>Both morphological and functional abnormalities of the platelets from the patient were clearly distinguishable from that of other hereditary giant platelet disorders. It would probably represent a novel platelet disorder which had not been reported to date.</p>