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Treatment Free Remission for Chronic Myeloid Leukemia in 2017
The improvement in 10-year survival for chronic myeloid leukemia (CML) patients from ∼20% in the 1990s to over 80% today has been achieved with the clinical application of tyrosine kinase inhibitor (TKI) therapy targeting Bcr-Abl. Despite the improvements in outcomes achieved with TKI therapy, major challenges still confront the CML clinician. De-novo blast crisis or transformatio n to blast crisis is still seen in ∼10%, similar numbers are resistant to all TKIs and only ∼50% overall achieve deep molecular responses (DMR). (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Timothy P. Hughes Source Type: research

Novel Therapeutic Options in CML
Tyrosine kinase inhibitors (TKIs) have turned chronic myeloid leukemia (CML) from a life-threatening malignancy worth the risk of an allogeneic stem cell transplant into a chronic condition. For most patients with chronic phase CML (CP-CML) life expectancy is now dictated by co-morbidities. As a result treatment paradigms for CML are changing, with more emphasis on quality of life, avoidance of long-term TKI toxicities and treatment free remission (TFR) as the key therapy objective rather than overall survival (OS). (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Michael Deininger Source Type: research

BCR-ABL Negative CML-Like Disorder
Chronic myeloid leukemia (CML) has been defined for many years as BCR-ABL positive disease only, but older publications refer to a poor prognosis, clinically heterogeneous entity termed ‘BCR-ABL negative CML’ constituting about 5% of CML cases. Apart from very rare CML cases with cytogenetically cryptic, atypical variant BCR-ABL fusions that had been inadvertently missed during the diagnostic work up, most of these cases would now be classified as a subtype of myelodysplastic/m yeloproliferative neoplasm (MDS/MPN) such as atypical CML (aCML), chronic myelomonocytic leukemia (CMML) or chronic neutrophilic leukem...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Nick Cross Source Type: research

When to Consider an Allograft in Chronic Myeloid Leukemia
Tyrosine kinase inhibitors (TKI) are now the treatment of choice for all newly diagnosed patients with chronic myeloid leukaemia (CML)1. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Eduardo Olavarria Source Type: research

BCL-2 Inhibition in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is the most common adult acute leukemia, and most patients die from their disease. Most older patients do not tolerate induction chemotherapy, and there are few effective therapies for relapsed/refractory disease. Novel approaches are needed. BCL-2 has been a promising target, and the recent clinical experience with venetoclax bring great promise. Here I summarize the rationale for and historical experience with targeting BCL-2, provide an overview of the venetoclax clinical data and speculate on its mechanism, and suggest future directions. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Daniel A. Pollyea Source Type: research

Novel Immunotherapy Approaches in AML: Focus on Monoclonal Antibodies
Monoclonal antibody (mAb)-based therapies have become an important modality for cancer treatment but have had limited success to date in acute myeloid leukemia (AML). Identification of new antigenic targets and antibody engineering techniques may overcome the modest anti-leukemic effects seen with most native antibodies studied previously in AML. Advances in bispecific immune-engaging antibody technology may improve the pharmacology of these agents, and the safety and efficacy of antibody-drug conjugates (ADCs) may be enhanced by better cytotoxic payloads and chemical linkers. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Joseph G. Jurcic Source Type: research

Nuclear Transport Inhibition in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a clonal hematopoietic disorder characterized by a block in myeloid differentiation and aberrant proliferation of immature myeloid progenitors. Chemotherapy resistance is an inherent feature of self-renewing leukemia-initiating cells (LICs), and is what leads to disease relapse in the majority of AML patients. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Kendra Sweet Source Type: research

Novel Chemotherapeutics in AML
Over the past several decades, despite advances in understanding the biology of AML, the standard therapy for patients with this disease has changed very little with the notable exception of the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in the therapy of acute promyelocytic leukemia (APL). The combination of cytarabine and an anthracycline continues to be the basis for most induction and consolidation regimens in other types of AML. Older patients with AML, particularly the septa and octogenarians and those with comorbid conditions, are less able to tolerate the traditional cytotoxic chemoth...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Farhad Ravandi Source Type: research

Case Study: Treatment Decisions in Secondary AML
A 67 year old female with history of hypertension, hyperlipidemia, and diabetes mellitus with secondary AML is referred for consultation. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Jessica K. Altman Source Type: research

Debate: Should MRD Monitoring in AML Be Routine? Pro
Initial formal criteria, based on microscopic evaluation of the bone marrow and blood as well as patient examination, to define treatment responses such as “complete remission” (CR) in acute myeloid leukemia (AML) were proposed over 60 years ago. These criteria have remained essentially unchanged over time and continue to serve as standard for response assessment, as surrogate endpoint in early-phase clinical trials, and as basis for clinical decis ion-making. Because relapse from morphologic CR is common, however, much effort has focused over the last 40 years on strategies to detect submicroscopic, “min...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Roland B. Walter Source Type: research

Debate: Should MRD Monitoring in AML Be Routine? Con
Morphologic review of the bone marrow of patients with Acute Myeloid Leukemia (AML) is used for the assessment of response to therapy. Nadir biopsies are often done to determine if patients should receive additional induction therapy and marrow biopsies on count recovery are done to determine remission status. In order to be considered in morphologic complete remission, patients much have adequate cellularity in the marrow with (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Selina Luger Source Type: research

AML: The Next Question
For younger patients, of whom 45-50% are cured by chemotherapy, it is likely that chemotherapy will remain as the core of treatment for the foreseeable future. Hopefully efforts will still be made to refine chemotherapy and move beyond the “3+7” approach. The several new none-chemotherapy agents are likely to be added to the chemotherapy backbone. There is a tactical challenge in older patients where it could be argued that the chemotherapy backbone is much less successful. Here, and in older patients who have objective evidence o f prohibitive co-morbidity, more dramatic changes are justifiable such as up-fron...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Alan K. Burnett Source Type: research

Molecular Determinants of Response in AML
Clinical, cytogenetic, and gene-based studies have been used to inform biology and improve prognostication for patients with acute myeloid leukemia (AML), myelodysplasia (MDS), and myeloproliferative neoplasms (MPN). Most recently, a series of candidate gene and whole genome studies have identified recurrent somatic mutations in AML patients including TET2, ASXL1, DNMT3A, and cohesin complex mutations. Moreover, these mutations can be used to improve risk stratification in AML independent of established clinical parameters. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Ross L. Levine Source Type: research

Multiple Myeloma: State of the Art
The treatment of newly diagnosed myeloma is a moving target given the rapid and important advances in the understanding of disease biology as well as a wealth of new agents with which to treat the disease. As such, it is important at the time of initial presentation, to have a defined treatment plan that includes induction, consolidation and maintenance therapy in order to maximize duration of initial response. Along the same lines, in the relapsed disease setting, following defined treatment approaches allows one to maximize treatment benefit and prolong duration of subsequent remissions. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Sagar Lonial Source Type: research

Management of Early Relapse, How to Navigate the Choices
Treatment of relapsed and/or refractory multiple myeloma (RRMM) is always a challenge for the hematologist. Over the last 5 years, a spectrum of novel therapies with different mechanisms of action, including second generation proteasome inhibitors (carfilzomib and ixazomib), third-generation immunomodulatory drugs (pomalidomide), a histone deacetylase inhibitor (panobinostat) and monoclonal antibodies (mAbs) (elotuzumab and daratumumab) has transformed our approach to the treatment of patients with RRMM. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Meletios A. Dimopoulos, Maria Gavriatopoulou, Evangelos Terpos Source Type: research

Immune Therapy for Multiple Myeloma
For many years the application of immune therapy to multiple myeloma (MM), with the limited exception of allogeneic stem cell transplantation, lagged behind other hematologic malignancies. However, the introduction of immune-modulating drugs (e.g. lenalidomide, pomalidomide), which have multiple anti-neoplastic properties, opened an era where the role of immune therapy plays an important and growing role in the treatment of newly diagnosed and relapsed/refractory (RR) MM. Recently, monoclonal antibodies targeting CD38 (daratumumab) and SLAMF-7 (elotuzumab) have received approval for RR MM. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Michael R. Bishop Source Type: research

The Role of Consolidation and Maintenance in Multiple Myeloma
The last two decades witnessed great strides in myeloma therapeutic approaches, ultimately resulting in significant improvement in clinical outcomes. A better understanding of the plasma cell biology allowed for identifying putative targets in myeloma leading to the development of newer classes of drugs with enhanced anti-myeloma activity. During the same time period, we also gained a better understanding of the clonal evolution of myeloma and recognized the need for a continuous sustained suppression of these clones to prevent disease relapse. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Ajay K. Nooka Source Type: research

Identifying the Right Patient for Bcl2 Inhibition in Myeloma
Despite the significant improvements in the recent years in terms of new therapies for multiple myeloma, the disease eventually becomes refractory to existing therapies and new approaches based on better understanding of the disease biology are required. Apoptotic pathways are a bona fide target for cancer therapeutics, given its central role in cancer cell survival. There are two main pathways of apoptosis or programmed cell death namely the extrinsic pathway, or death receptor mediated pathway and the intrinsic, or the mitochondrial pathway1. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Shaji Kumar Source Type: research

Monoclonal Antibody Therapy for Multiple Myeloma: Progress and Clues for Response
This review describes the on-going progress with development and use of monoclonal antibody therapy in multiple myeloma. Additional novel immunotherapies are imminent. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Tom Martin Source Type: research

Risk Assessment and Diagnostic Criteria
Plasma cell dyscrasia is a spectrum of illness caused by either clonal proliferation of plasma cells and/or monoclonal paraprotein. Clonal proliferation of plasma cells can lead to monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma or asymptomatic myeloma, or multiple myeloma. Recent progress has resulted in better understanding of the biology of the disease. This has warranted changes to the diagnostic criteria and risk stratification. This abstract presents the latest on biology, diagnosis, and risk stratification for MGUS, smoldering myeloma, and multiple myeloma. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Sundar Jagannath Source Type: research

Hodgkin Lymphoma Treatment: State-Of-The-Art
The last decade has seen exciting developments in the field of Hodgkin lymphoma therapy. Several large randomized trials have confirmed the benefit of a PET response-adapted strategy for the treatment of newly diagnosed Hodgkin lymphoma, and three drugs have received FDA approval for the treatment of relapsed/refractory disease. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Robert Chen Source Type: research

New Strategies for the Treatment of Early Stage Classical Hodgkin Lymphoma (cHL)
Early stage classical Hodgkin lymphoma (cHL) has a high rate of cure for patients for are interim PET/CT-2 or 3 negative (1, 2) Thus, given this there is an increased focus on treatment de-escalation for patients with a negative interim PET/CT scan including decreasing number of cycles of chemotherapy, adding in biologic therapies, and decreasing radiation ranging from decreasing radiation doses and field sizes to eliminating radiation. However, for patients who have residual disease activity on interim PET/CT (1,  2) the outcomes remain challenging in that often ultimately these patients develop refractory disease th...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Raphael E. Steiner, Michelle A. Fanale Source Type: research

Relapsed and Refractory Hodgkin Lymphoma
The management of relapsed and refractory (rel/ref) Hodgkin lymphoma (HL) has changed dramatically with the availability of brentuximab vedotin (BV) and checkpoint inhibitors. The data leading to approval of these agents and their incorporation into the treatment paradigm of rel/ref HL will be discussed. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Alison Moskowitz Source Type: research

Non-Hodgkin Lymphoma – State of the Art and Next Questions
The diseases we call non-Hodgkin lymphoma represent a wide variety of pathological and clinical entities. With developing insights into the biology of these disorders they are being divided into increasingly uniform subgroups requiring specific treatment approaches. Treatment results have steadily improved and for most subgroups there is some chance for cure with available treatments. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: James O. Armitage Source Type: research

Treatment of Relapsed DLBCL
Approximately one third of patients with DLBCL will relapse and require second line therapy. Currently patients are stratified by those who are candidates for high dose chemotherapy with curative intent, or patients who are not candidates for high dose chemotherapy and area managed palliatively. Patients who are sufficiently young and fit for intensive therapy undergo second line treatment with a non-cross-resistant chemotherapy regimen such as R-ICE, R-DHAP, or R-GDP, each of which has similar efficacy in this setting. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Jeremy S. Abramson Source Type: research

Treatment of Marginal Zone Lymphoma
The margin is a part of the lymphoid follicle, the splenic white pulp or a mucosa associated lymphoid area where antigen influx occurs. Associations of antigen presentation influence the pathogenesis, pathophysiology and treatment of the disease. This is also true of the three major subtypes: nodal, splenic and extra-nodal disease. Autoimmunity, chromosomal translocations and distinct microbial pathogens are all implicated in the pathogenesis of MZL. Patients with known infectious origins should be treated for those specific infections appropriately before consideration of other therapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Ariela Noy Source Type: research

Case Study: T-Cell Lymphoma
The management of T-cell lymphoma is challenging. Especially for those with recurrent disease, there is no standard therapy available, and the prognosis is dismal. The treatment therefore has to be individualized, dependent on the histology of lymphoma, response to previous treatment, patients' overall condition and the eventual goal. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Yasuhiro Oki Source Type: research

Primary Mediastinal B-Cell Lymphoma
Primary Mediastinal Diffuse Large B-cell Lymphoma (PMBL) was initially described in the 1980s as a distinct clinicopathologic entity1. Since that time, our understanding of PMBL disease biology has increased dramatically and modern therapeutic regimens are associated with high cure rates. Clinically, PMBL presents as a rapidly growing dominant mediastinal mass, frequently accompanied by local invasion, pericardial/pleural effusions and superior vena cava syndrome; extranodal involvement at presentation is uncommon and bone marrow is almost never involved2. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Paul A. Hamlin Source Type: research

Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) accounts for approximately 6% of all Non-Hodgkin lymphoma (NHL) with a median age at presentation of around 70 years. It is characterised by the t(11;14)(q13:32) translocation which leads to overexpression of cyclin D1 resulting in subsequent dysregulation of the cell cycle and of several intracellular survival pathways. Although the survival of MCL patients has been demonstrated to have improved over the last decade it remains incurable, typically relapsing multiple times with increasingly chemotherapy refractory disease. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Simon Rule Source Type: research

Therapeutic Antibodies Need To Interact With Fc Receptors
When Rituxan, the first monoclonal antibody for the treatment of cancer was developed, it became clear that its mechanism of action involved the Fc receptor. We noticed that the likelihood of tumors to respond was greatly influenced by which of the two different forms of the Fc receptor gene (CD16) the patient had. One form was known to bind better to the Fc portion of the therapeutic antibody and patients who had this form had a higher tumor remission rate. This result was concordant with the now classical report by Clynes and Ravetch on the role of the Fc receptor (CD16) in the therapy of Rituxan against human tumors tra...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Ronald Levy Source Type: research

Peripheral T-cell Lymphomas: Considerations for Frontline Therapies
Peripheral T-cell lymphomas (PTCL) continue to present a significant clinical challenge both at the time of initial diagnosis and during the relapse. A proportion of patients with PTCL diagnoses can achieve cure or long-term disease control; hence, in the majority of cases, the intent of initial therapy is curative. However, given the advanced age at the time of diagnosis in the majority of PTCL cases, palliative intent frontline therapy should also be explored for a sizable proportion of patients. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Andrei Shustov Source Type: research

Progress and Challenges in the Treatment of Follicular Lymphoma
Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma. The disease is characterized by a very heterogeneous natural history ranging from an indolent course not requiring therapeutic interventions at the time of diagnosis to a more aggressive clinical behavior with poor or only brief and transient response to therapy. Transformation to aggressive lymphoma may occur. Recent advances in supportive measures and novel therapeutic approaches have markedly improved survival of FL patients. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Izidore S. Lossos Source Type: research

T Cell Lymphoma: Relapsed Disease
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders derived from post-thymic T cells and natural killer cells. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Barbara Pro Source Type: research

First Line Management of Follicular Lymphoma
The first line therapy of follicular lymphoma can be subdivided into three main subtypes: the management of localised disease, of asymptomatic advanced stage disease, and of symptomatic advanced stage disease. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Robert Marcus Source Type: research

Chemotherapy for MCL Debate: The Positive Side
Mantle cell lymphoma (MCL) is a heterogeneous disease that cannot be treated with uniform regimens. Aggressive MCL (blastoid, pleomorphic, bulky tumor mass> 7 cm, high Ki-67, TP53 mutation/deletion, c-myc and NOTCH positivity) cannot be treated with single agents alone and needs to be treated with combination chemotherapy, combinatory biological agents, cellular therapy, or “mini” stem cell transplantation. In daily routine practice, we treat young, fit MCL patients and elderly MCL patients differently. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Luhua Michael Wang Source Type: research

Hematopoietic Cell Transplantation As Curative Therapy for Patients With Myelofibrosis: When, Who and How ?
Allogeneic hematopoietic cell transplantation (HCT) is currently the only treatment with curative potential for patients with myeloproliferative neoplasms (MPN).Classification by the Dynamic International Prognostic Scoring System (DIPSS) or by the expanded DIPSS plus is reflected in post-transplant outcome. Retrospective comparisons (in patients with primary myelofibrosis [PMF]) suggest that while patients in the DIPSS categories low and intermediate-1 have a superior life expectancy with conservative management, patients with intermediate-2 or high risk disease clearly benefit from HCT. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: H. Joachim Deeg Source Type: research

CD19 Chimeric Antigen Receptor-Modified T Cell Immunotherapy in Ibrutinib-Refractory Chronic Lymphocytic Leukemia
Ibrutinib, an inhibitor of Bruton Tyrosine Kinase (BTK) induces partial responses (PR) in a majority of patients with chronic lymphocytic leukemia (CLL). However, complete responses (CR) are infrequent and the survival of high-risk patients who progress on ibrutinib is short. Venetoclax, a BCL-2 inhibitor, has shown anti-tumor activity in a subset of patients who failed ibrutinib therapy, but CR is rare and the durability of these responses is unknown. We performed a phase 1/2 open label clinical trial with a primary objective of evaluating safety and feasibility of anti-CD19 CAR-T cell immunotherapy in patients with B cel...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Cameron Turtle Source Type: research

Managing BTK Inhibitor-Refractory CLL
The B cell receptor (BCR) signaling pathway is composed of several protein kinases that, in CLL, deliver activation and survival signals thereby participating in the prolonged survival of the malignant clone. These kinases were targeted with small molecule inhibitors, which have revolutionized treatment and remarkably improved survival for patients with CLL. One such kinase, Bruton ’s tyrosine kinase (BTK), is irreversibly inhibited by ibrutinib. Ibrutinib covalently binds to C481 of BTK and is currently the only approved BTK-inhibitor, including as initial and salvage therapy for CLL. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: William G. Wierda Source Type: research

Prognostic and Predictive Markers in CLL
In spite of important progress in their management, survival of patients with CLL is highly variable and ranges from less than 5 years to a normal lifespan. Developed more than 30 years ago, clinical staging systems independently devised by Rai et al. and Binet et al. based on physical examination and blood cell counts have been the mainstay for estimating prognosis in patients with CLL. Afterwards, many other parameters have shown prognostic value in patients with CLL, among them IGHV mutational status, FISH-detected cytogenetic abnormalities, blood lymphocyte doubling time, cell markers (e.g. (Source: Clinical Lymphoma, ...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Emili Montserrat Source Type: research

Does Adding Chemo to BTK Inhibitors Have a Real Benefit?
The advent of BTK inhibitors has revolutionized the therapy of CLL in the last several years. The first in class covalent BTK inhibitor ibrutinib was studied as a single agent in its pivotal registration trials, against chlorambucil in the frontline setting and against ofatumumab in the relapsed setting. Early phase 1b data did establish that ibrutinib could be safely combined with both bendamustine rituximab (BR) and fludarabine cyclophosphamide rituximab (FCR). The combination with BR led to the pivotal HELIOS trial, in which relapsed CLL patients without 17p deletion were randomized to BR or BR-ibrutinib. (Source: Clini...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Jennifer R. Brown Source Type: research

Next Generation Small Molecules
The first generation of B cell receptor inhibitors has dramatically changed the treatment landscape for CLL and provided effective non-chemotherapy options for patients with CLL. Ibrutinib, a BTK inhibitor, and idelalisb, a PI3K inhibitor ( plus rituximab) produce high response rates and are minimally myelosuppressive.1,2 They have distinct toxicity profiles that are different. The most common toxicity with ibrutinib is diarrhea, but this is generally mild and often self-limited. Rare but serious side effects include bleeding and atrial fibrillation. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Susan O ’Brien Source Type: research

Preclinical Studies in CAR T Cell Development
T cells that express chimeric antigen receptors (CARs) have shown remarkable efficacy against CD19 expressing hematological tumors1-3. Patients receive autologous T cells that are typically virally transduced to express a CAR that can recognize a specific antigen expressed on the surface of tumor cells and generates large numbers of effective tumor-specific T cells. The value of preclinical models is to establish some evidence for efficacy, uncover potential toxicities, and to study the mechanism of action. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Charles L. Sentman Source Type: research

Therapeutic TCR Mimic Monoclonal Antibodies to Intracellular Oncogenic Proteins
Nearly all tumor-specific targets and oncogenic proteins are intracellular proteins. Few are druggable with current small molecules. Neither mAb nor mAb-directed CAR T cells can enter the cell to recognize these proteins. In contrast, naturally occurring T cells are evolved to recognize MHC-presented peptide epitopes from intracellular proteins. These are generally derived from intracellular proteins. Therefore, there is a need to create antibodies that recognize antigens from intracellular, tumor specific and oncogenic proteins. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: David A. Scheinberg Source Type: research

Distinguishing CHIP from Myeloid Neoplasia
Peripheral blood develops from the hematopoietic stem cell (HSC), which is defined by its capacities for sustained self-renewal and multi-lineage differentiation. Normally, a diverse pool of HSCs is maintained in homeostatic balance and contributes to polyclonal hematopoiesis. Age-related development of clonally restricted hematopoiesis has been demonstrated by recent genetic studies in large populations of healthy individuals.1-3 During normal aging, individual HSCs steadily accumulate somatic mutations. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: R. Coleman Lindsley Source Type: research

Hematology – Leading the Way
When I was elected to be President of SOHO, I was promised by Dr. Kantarjian that it was going to be a relatively light-workload experience. However, one of the requirements for the President is to develop an extended summary of hematologic malignancies, where we have been, where we are, and where we are going. In this era when the technology has expanded at a rapid rate leading to development of new agents mainly by the pharmaceutical industry, the complexity of writing such a summary has been complicated to say the least. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Michael J. Keating Source Type: research

Novel Targets in the AML Microenvironment
Michael Andreeff1, Venkata L.Battula1, Xiangmeng Wang1, Po Yee Mak1, Mu Hong1, Wenjing Tao1, Vivian Ruvolo1, Jonathan Pachter3, David Weaver3, Bing Xu5, Sujan Piya1, Seemana Bhattacharya 1,Phuong M. Le1, Jeffrey C. Sun1,Sonali Sonnylal1,Teresa McQueen1,Xiaoyang Ling1, Rodrigo Jacamo1, Zhigiang Wang5,Gheath Al-Altrash4, Arvind Rao7, R.Eric Davis6,Carlos Bueso-Ramos9, Yoko Tabe10, Gautam Borthakur1, Marina Konopleva1, Bing Z Carter1 (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Michael Andreeff Source Type: research

Editorial Board/Masthead
(Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Source Type: research

Table of Contents
(Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Source Type: research

Author Index
(Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Source Type: research

Subject Index
(Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Source Type: research