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.

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.

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.

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.

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.

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.

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.

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.

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.

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.