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Myelofibrosis with Cytopenias
Cytopenias represent a frequently encountered and often difficult clinical problem in patients with myelofibrosis (MF), and are usually more pronounced in patients with primary myelofibrosis (PMF) than those with post-polycythemia vera (post-PV) or post-essential thrombocythemia (post-ET) MF. Anemia is present in approximately 30% of patients with PMF at diagnosis and eventually develops in essentially all patients. While severe thrombocytopenia (platelets (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Prithviraj Bose Source Type: research

What Can Your Radiation Oncologist Do Today: Technology at Your Service to Maximize the Therapeutic Ratio
Treatment of Hodgkin ’s lymphoma has seen an impressive improvement in the survival over the past five decades. Major part of that improvement is credited to avoiding treatment toxicity, which is considered an equal leading cause in long-term mortality. Combined modality with chemotherapy and radiation remains the acc epted standard of care especially for early stage presentation. The use of radiation has been critically looked at, in view of the previously reported side effects, cardiac and second malignancies, therefore prompted a radical change in radiation therapy techniques. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Bouthaina Dabaja Source Type: research

Management of Lower Risk Non-del(5q) MDS
Myelodysplastic syndromes (MDS) are prognostically stratified into lower risk (LR MDS) and higher risk ones, according to the International prognostic scoring systems (both IPSS and IPSS-R)(1,2). IPSS-R prognostic evaluation is based on depth f cytopenias but mainly on cytogenetic abnormalities and the risk is defined as the overall survival and propensity to develop acute leukemia. The great majority of MDS patients belong to lower risk categories, but within such broad definition there are different forms of MDS with quite divergent outcomes. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Valeria Santini Source Type: research

Is MRD Useful in CLL
On July 1, 2016 the EMA approved the use of undetectable MRD in CLL patients as an intermediate endpoint for licensure in well controlled clinical trials. The evidence for MRD as an intermediate endpoint is primarily based on studies using harmonised multicolour flow cytometry protocols developed by an international collaboration led by the European Research Initiative on CLL (ERIC). The flow cytometry 4-color-based approach has become the gold standard in prospective clinical trials. In more recent work by the ERIC (Rawstron et al, Leukemia, 2016), a simplified 6-color, one-tube version of the protocol has been reported a...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Paolo Ghia Source Type: research

Other Cancers in CLL, a Common Problem
Chronic lymphocytic leukemia (CLL), the most common leukemia in the western world, is primarily a disease of older individuals. Most patients with CLL enjoy a long life expectancy and, in up to one third of cases, never require any treatment.1 When therapy is needed, a variety of highly effective agents is available and produces complete and sustained remission in a large proportion of cases, resulting in long-term survival.2 (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Lorenzo Falchi, Alessandra Ferrajoli Source Type: research

Next Generation Chimeric Antigen Receptor (CAR) T Cells
T cells may be genetically modified to express chimeric antigen receptors (CAR) targeted to antigens expressed by tumor cells. We have developed this technology in the laboratory and translated this adoptive T cell approach in the clinic. Recently published reports support the novel approach of treating cancer with patient derived T cells genetically modified to express artificial T cell receptors targeted to tumor associated antigens. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Renier Brentjens Source Type: research

Single Cell Analysis for Drug Discovery and Development
The genetic, functional or compositional heterogeneity of healthy and diseased tissues presents major challenges in drug discovery and development. Such heterogeneity hinders the design of accurate disease models and can confound the interpretation of biomarker levels and of patient responses to specific therapies. The complex nature of virtually all tissues has motivated the development of tools for analyzing statistical numbers of single cells at the genome, transcriptome, proteome, and even metabolome levels. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: James R. Heath Source Type: research

Co-Stimulatory Regulation of CAR T Cell Function
A major advance for anti-cancer T cell therapy is the chimeric antigen receptor (CAR), which is a single chain variable fragment (scFv) derived from an antibody fused to the signaling domains of a T cell receptor (TCR) [1]. The intracellular domain of a first-generation  CAR includes only CD3ζ, while second-generation CARs also include co-stimulatory domains such as CD28 or 41BB. These second-generation CAR domains support highly-efficacious tumor killing in mice and led to the clinical evaluation of CAR T cell therapies in patients. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Justin C. Boucher, Marco L. Davila Source Type: research

Immune Checkpoint Based Approaches in AML
This manuscript was supported in part by the MD Anderson Cancer Centre Leukaemia Support Grant (CCSG) CA016672 and the MD Anderson Cancer Center Leukemia SPORE CA100632. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Naval Daver, Guillermo Garcia-Manero, Pam Sharma, James Allison, Hagop Kantarjian Source Type: research

The Impact of the Microbiome on Outcomes of Stem Cell Transplant
In recent years, increased ease and reduced costs of characterizing the composition of the microbiome has led to an examination of its impact on a variety of clinical outcomes. We discuss the results of studies that have focused on outcomes after allogeneic stem cell transplant. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Robert Jenq Source Type: research

The Impact of the Microbiome on Infectious Outcomes in Patients with Hematologic Malignancy
Patients with hematologic malignancy are at high risk for serious infections. The vast majority of infections arise from organisms that are colonizing the gastrointestinal tract which gain access to sterile sites via disrupted epithelial barriers. There is an emerging understanding that the ability of bacterial pathogens, including multidrug resistant organisms, to colonize and subsequently infect patients with hematologic malignancy is largely dependent on protective bacterial species present in the gastrointestinal tract, aka the microbiome. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Samuel A. Shelburne Source Type: research

Advances in the Pathology of High Grade B Cell Lymphomas
“B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL)”, abbreviated as “BCLU” here, was one of the new categories introduced in the 2008 WHO classification.1 However, this “BCLU” category has been eliminated i n the 2016 Revision of WHO classification of lymphoid neoplasms and replaced by two new categories of high grade B cell lymphoma (HGBL).2 One is HGBL, NOS, which include cases in previous BCLU category but without a MYC and BCL2 and/or BCL6 rearrangement and cases that appear blastoid but not diagno stic...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Shaoying Li, Pei Lin, Carlos Bueso-Ramos, L. Jeffrey Medeiros Source Type: research

Breast Implant-Associated Anaplastic Large Cell Lymphoma: An Update
Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a T-cell lymphoma, that arises around breast implants and is considered a provisional entity in the 2016 revision of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues.1 Most patients present with an effusion around the breast implant, with the lymphoma cells usually confined by the capsule around the implant and most patients are cured by removal of the implants and complete excision of the capsule. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Roberto N. Miranda Source Type: research

Treatment of Adult Acute Lymphocytic Leukemia (ALL) in 2017
In pediatric ALL, intensive multi-modal combination chemotherapy with induction-consolidation-maintenance-intrathecal chemotherapy (2.5 to 3 years) results in cure rates of 80 to 90%. In adult ALL, similar regimens result in cure rates of 40 to 50%. Therefore additional modalities are needed to increase the cure rates 1. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Elias Jabbour, Hagop Kantarjian Source Type: research

New Discoveries in Biology and Molecular Markers
Approximately 25% of childhood ALL cases, and a higher proportion of adult ALL cases, lack a unifying chromosomal alteration on cytogenetic analysis. Several new subtypes of B-ALL have been recently described that exhibit distinct leukemic cell gene expression profiles, but diverse, often cytogenetically cryptic founding alterations (Figure 2). (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Charles G. Mullighan Source Type: research

Progress in the Study of Pediatric ALL
Contemporary minimal residual disease (MRD)-directed therapy together with improved central-nervous-system leukemia control and supportive care have increased 5-year survival rate above 90% in childhood acute lymphoblastic leukemia (ALL).1 Some of the recent advances in biology and treatment of childhood ALL will be mentioned in this review. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Ching-Hon Pui, St. Jude Source Type: research

Monoclonal Antibodies in Acute Lymphocytic Leukemia
Therapies targeting either specific transcripts (e.g. BCR-ABL1 tyrosine kinase oncoprotein by tyrosine kinase inhibitors) or specific leukemic cell surface antigens (e.g. CD20, CD22, and CD19 monoclonal antibodies) are major breakthroughs in the treatment of acute lymphocytic leukemia (ALL). Monoclonal antibodies hold significant promise in improving the outcomes of patients with ALL. Rituximab has been shown to improve overall survival in patients with CD20-positive ALL, and next-generation anti-CD20 antibodies may be able to further improve these outcomes. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Elias Jabbour, Hagop Kantarjian Source Type: research

Use of MRD for Selection of Post Remission Therapy in Adult All Management
After frontline induction therapy, the complete remission (CR) rate is achieved in around 90% of newly diagnosed adults with ALL, irrespectively of the regimen administered (BFM-derived or HyperCVAD-based). However, relapse remains the main cause of treatment failure in adults with ALL, and half of the adults who achieve CR will relapse. Thus, CR is not a good surrogate marker for long-term outcomes in ALL. Minimal residual disease (MRD) refers to the ability to detect and quantify small residual clones of leukemic cells not detected by morphology at any time during or after the treatment of ALL. (Source: Clinical Lymphoma...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Josep-Maria Ribera Source Type: research

T-cell ALL: New Insights to the Biology
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy caused by the accumulation of genomic lesions that affect the development of T cells. For many years, it has been established that deregulated expression of transcription factors (TAL1, LMO1, TLX1/3, NKX and HOXA), impairment of the CDKN2A/2B cell-cycle regulators, and hyperactive NOTCH1 signaling play prominent roles in the pathogenesis of this leukemia.1,2 (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Jan Cools Source Type: research

CAR T-Cell Therapies: Overcoming the Challenges and New Strategies
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape for patients with advanced lymphoid malignancies. Response rates up to 90% have been reported for patients with refractory B-lineage acute lymphoblastic leukemia (ALL).1-4 Much has been learned since the excitement of the first reported case using CAR T cell therapy for the successful treatment of a patient with multiply relapsed chronic lymphocytic leukemia (CLL).5 Pre-clinical and clinical trials are underway in other malignancies, including multiple myeloma, acute myeloid leukemia, and solid tumors. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Partow Kebriaei Source Type: research

Clonal Hematopoiesis and MDS Risk
Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the clonal population of hematopoietic cells that are often characterized by the detection of somatic mutations in one of the cancer genes. It has strong associating with aging and prevalence of CHIP can be as high as 20% in individuals with age above 80s. Most frequently mutated genes in CHIP are DNMT3A followed by TET2 and ASXL1. Individuals with CHIP have an increased risk of developing hematologic malignancies such as MDS or AML, although the actual risk is relatively low. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Koichi Takahashi Source Type: research

The NLRP3 Inflammasome as a Driver of the MDS Phenotype
Myelodysplastic syndromes (MDS) share features of cytological dysplasia and ineffective hematopoiesis while demonstrating profound molecular and genetic heterogeneity. Our investigations show that many of the hallmark features of MDS arise from activation of the NLRP3 inflammasome that directs clonal expansion and pyroptotic cell death, a caspase-1 –dependent pro-inflammatory, lytic form of cell death. Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPC) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct the activation of caspase-1, IL-1β and IL-18 generat...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Alan List Source Type: research

Myelodysplastic Syndromes Debate: Should Molecular Genetics Guide the Decision for Allogeneic Transplant - Pro
Allogeneic transplantation is the only curative therapy for the Myelodysplastic Syndromes (MDS). Older prognostic systems such as the IPSS and IPSS-R can help determine the appropriateness of allogeneic stem cell transplantation (SCT), however the incorporation of molecular genetic profiling in MDS can allow us to refine our decision making process – not only to help decide who should undergo SCT, but how they should undergo SCT. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Corey Cutler Source Type: research

Should Molecular Genetics Guide the Decision for Allogeneic Transplant? - Con
Classically, the indication and timing of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with myelodysplastic syndromes (MDS) is based on the individual risk score obtained by applying the original International Prognostic Scoring System (IPSS) or its recently revised version (IPSS-R).1-3 Those scoring systems use three disease-related characteristics: chromosomal abnormalities, percentage of blast cells in bone marrow, and number and severity of cytopenias.1,2 Allo-HCT at diagnosis is recommended for higher-risk patients whereas transplantation for lower-risk MDS is usually delayed until there are s...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Guillermo F. Sanz Source Type: research

Emerging Therapies and Clinical Challenges in Chronic Myelomonocytic Leukemia
Chronic Myelomonocytic Leukemia (CMML) is a lethal myeloid neoplasm with no therapies that improve its dismal natural history. CMML is characterized by peripheral monocytosis, bone marrow dysplasia, and a propensity for AML transformation. CMML has long been classified as a subtype of the Myelodysplastic Syndromes (MDS) until 2008 when the World Health Organization (WHO) consolidated a group of diseases, including CMML, into a new category known as Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPNs)1. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Eric Padron Source Type: research

State of the Art Update: Molecular Genetics of MPN
The molecular basis of myeloproliferative neoplasms (MPN) has been defined in almost all cases. In greater than 95% of cases of MPN the mutations that drive the development of an MPN phenotype are accounted for by somatic mutations in three genes: JAK2, CALR or MPL, and notably these mutations occur in a mutually exclusive manner1. Mutations in JAK2 and MPL occur as gain-of-function point mutations (i.e. JAK2V617F and MPLW515L/K respectively), while the mutations in CALR occur as +1 base pair frameshifts in the last coding exon of CALR, which result in the generation of a novel C-terminus1,2. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Ann Mullally Source Type: research

Understanding New WHO Classification of MPNs
The 2016 multiparameter WHO (World Health Organization) classification for Philadelphia-negative myeloproliferative neoplasms (MPNs) integrates clinical features, morphology and genetic data to diagnose polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), now subgrouped into prefibrotic PMF and overt PMF.1 (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Francesco Passamonti, Barbara Mora, Margherita Maffioli Source Type: research

Therapy of Myelofibrosis: Where We Are and What Next
Treatment of myelofibrosis has greatly improved since the approval of the Janus kinase (JAK) inhibitor ruxolitinib more than 5 years ago. However, it has become clear that inhibition of JAK-STAT signaling alone is not a curative strategy. Therefore, rational combination of ruxolitinib with agents targeting other signaling pathways that are dysregulated in myelofibrosis is an attractive strategy. Several clinical studies testing ruxolitinib in combination with other agents are now underway. The rationale for and early results of clinical studies of ruxolitinib-containing combination therapies will be discussed. (Source: Cli...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Srdan Verstovsek Source Type: research

Case Study: Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis
Allogeneic Hematopoietic Cell Transplantation (HCT) is the only curative therapy for myelofibrosis (MF). Traditionally, HCT has been limited by the availability of donor sources. In 2017, almost every patient who needs HCT is able to find a donor. In this section, we explore the trends in HCT for MF, including the use of alternative donor grafts. We will also discuss special issues related to splenectomy and leukemic transformation. New trends in HCT for MF including the use of genetic markers to select patients or predict outcomes will also be reviewed. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Karen Ballen Source Type: research

MPN: Next Questions: Potential New Targets for MPN beside JAK2
The discovery of activating JAK2 mutations changed the landscape of MPN treatment dramatically, quickly prompting the development of small molecule inhibitors of JAK2. First-generation JAK inhibitors are ATP-competitive antagonists of the JAK kinase domain and each inhibits the activity of one or more JAK isoforms to different degrees. Ruxolitinib, a dual JAK1/2 inhibitor, was the first of its class to be approved for treatment of primary myelofibrosis (PMF) and post-PV/ET MF. Treatment with ruxolitinib has been shown to reduce spleen size and alleviate systemic symptoms of MF1, although the myelosuppressive effects of rux...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Ann Mullally Source Type: research

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