Front-Line Vascular Access Devices in Acute Leukemias – Peripherally Inserted Central Catheter (PICC) Versus Traditional Central Venous Catheter (CVC): A Phase IV Randomized Trial (NCT02405728)
There is limited information on the feasibility and safety of peripherally inserted central catheter (PICC) as primary vascular access device in high-risk hematological patients for prolonged infusions of cytotoxic agents, blood products and/or other supportive therapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Claudio Cerchione, Maria Di Perna, Roberta Della Pepa, Novella Pugliese, Fabrizio Pane, Marco Picardi Source Type: research

CML Management in 2017
Chronic myeloid leukemia has evolved to become a highly treatable and potentially curable form of leukemia with the advent and optimal use of oral tyrosine kinase inhibitors (TKIs). Very mature data from landmark trials of first generation (imatinib), second generation (nilotinib, dasatinib, bosutinib) and third generation (ponatinib) TKIs are available and continue to shape treatment algorithms for initial treatment approach, response to suboptimal response or treatment failure, resistance and progressive disease and the more rare presentation or evolution to blast phase disease. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Michael J. Mauro Source Type: research

Targeted Therapy in AML: Something for Everyone?
Are the myeloid malignancies leading the way, based on our ability to easily obtain tumor tissue and success in CML, or are they following, given the use of multi-gene panels to treat upfront advanced lung cancer and the remarkable outcomes using check point inhibitors to treat formerly intractable solid tumors? Past achievements in the leukemias have been impressive but incomplete. In chronic phase CML we have essentially curative treatments; in myeloproliferative neoplasms we know the mutations but possess only partially effective therapies; and in myelodysplastic syndrome many mutations have been described but effective...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Richard Stone Source Type: research

Treatment Free Remission – The U.S Perspective
The treatment of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors has been the poster child in the drive to “personalize” cancer therapies by identifying vulnerable molecular targets in different cancers. The results in CML have been somewhat uniquely striking, likely in part because the bcr/abl mutation resulting from the 9;22 translocation is both necessary and sufficient to produce this myeloprolif erative disease in animal models whereas most other cancers have a well characterized “multi-hit” pathogenesis. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Charles A. Schiffer Source Type: research

Molecular Monitoring in the Treatment Free Remission Era
Molecular monitoring by of peripheral blood samples by serial quantification of BCR-ABL1 mRNA levels is an important therapeutic indicator for patients with chronic myeloid leukemia (CML) and is incorporated into both NCCN guidelines and ELN recommendations for patient management.1,2 Results are expressed on the International Scale (IS) for BCR-ABL1 mRNA measurement, access to which requires the derivation of laboratory-specific conversion factors (CFs) following sample exchange with a reference laboratory or the use of IS kits, systems or calibration reagents. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Nick Cross Source Type: research

Frontline Therapy in Chronic Myeloid Leukemia
The advent of tyrosine kinase inhibitors (TKIs) has drastically changed the treatment outcome of chronic myeloid leukemia (CML). Imatinib was the first TKI approved, and has been considered the standard of care for more than a decade. Second generation compounds, namely Dasatinib, nilotinib, and bosutinib are highly effective in newly diagnosed patients as well as those who fail imatinib. Second generation TKIs have been demonstrated to induce deeper and faster responses compared to imatinib, however no survival advantage has been observed so far. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Elias Jabbour Source Type: research

Clinical Applications and Pitfalls of MRD in ALL
Evaluation of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) is the most important parameter for treatment decisions (1). When assessed after induction/ consolidation therapy it determines the outcome. MRD negative patients have a survival probability of about 70% at 5 years or more, compared to 20% or less for patients remaining MRD positive (2). This is observed in several studies for Ph/ bcr-abl negative as well as for Ph/ bcr-abl positive patients (3). Adult patients remaining MRD positive require immediate action, since otherwise proceeding to a hematological relapse, which is difficult to treat ...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Dieter Hoelzer Source Type: research

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
The incorporation of tyrosine kinase inhibitors (TKIs) into chemotherapy regimens has significantly improved the outcomes of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Second and third generation TKIs with increased potency against BCR-ABL1 and enhanced activity against ABL1 kinase domain mutations have been evaluated in a number of studies showing significant promise. In particular, ponatinib, a potent pan-BCR-ABL1 TKI capable of overcoming the T315I mutation, is of significant interest in the treatment of Ph+ ALL, as a number of reports have shown a high incidence of T315I mutants at rel...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Farhad Ravandi Source Type: research

Update on Transplant in ALL
For many years, the use of blood and marrow transplant for adult patients with acute lymphoblastic leukemia (ALL) was primarily reserved for high-risk patients defined as those with a high white blood count, adverse cytogenetics, older age, and a delay in achieving remission. The landmark MRC UKALL XII/ECOG E2993 clinical trial also showed that patients with standard-risk ALL benefitted from allogeneic transplant in an intent-to-treat analysis.1 (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Mark R. Litzow Source Type: research

Application of NSG in Newly Diagnosed AML
Acute myeloid leukemia (AML) is a hematologic disease characterized by maturation arrest and proliferation of primitive clonal hematopoietic stem cells (blasts) resulting in bone marrow (BM) failure and eventually death if not timely treated. In 2017, approximately 20,000 new cases of AML and 10,000 disease-related deaths occurred in the United States alone. The median age at diagnosis is 67 years and the incidence of the disease increases with age. According to SEER/NCI database, survival in the US AML patients ’ population is 26.6% for the last 5 years. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Guido G. Marcucci Source Type: research

Acute Myeloid Leukemia in the Older Patient: Science or Craft?
Acute myeloid leukemia (AML) primarily affects older adults and yet outcomes have not significantly improved for this population, in fact – in the elderly population, less than half of patients are even offered therapy.1, 2 Many older, fit individuals can receive induction therapy, but outside of clinical trials, this patient population commonly receives monotherapy with a DNA-methyltransferase inhibitor.3 This treatment option is a ssociated with low response rates and only modest improvements in overall survival relative to supportive care alone. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Laura C. Michaelis Source Type: research

How and When to Use FLT3 Inhibitors
Activating mutations of the receptor tyrosine kinase FLT3 are one of the most common genetic lesions found in acute myeloid leukemia.1 The internal tandem duplication mutations (FLT3-ITD mutations) are found in 20-25% of newly-diagnosed cases and point mutations in the tyrosine kinase domain (FLT3-TKD), primarily at residue aspartate 835, are found in roughly 7% of cases. Shortly after they were discovered, it was recognized that the FLT3-ITD mutations were associated with an increased tendency to relapse and a resultant decreased overall survival probability, at least in the setting of conventional induction and consolida...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Mark Levis Source Type: research

Prognostic Models in AML
Assuming a person with acute myeloid leukemia (AML) wishes to receive AML-specific treatment, physicians must choose between conventional therapy, for example azacitidine, decitabine or “7+3”, and investigational therapy. Although results with most investigational therapies have not been superior to those seen with conventional therapies, the results of any relatively new trial are unknown; few patients have typically been enrolled, the enrolled patients are heterogeneous, and follow-up is short. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Elihu Estey Source Type: research

Management of Post ET/PV MF: Different from Primary MF
Clinical features of MF: PMF and SMF (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

Polycythemia Vera: When to Move from Hydroxyurea to Second Line Therapy
The hematologist ’s challenges when treating Polycythemia Vera (PV) include reduction in the risk of incident or recurrent thrombosis and/or hemorrhage, palliation of symptoms, minimization of long-term consequences of therapy, delay of progression and management during special situations, such as the peri-operati ve period.1 Often, cytoreduction is prescribed as a complement to phlebotomy and aspirin, with the intention of addressing these goals. Hydroxyurea (HU) is considered a first-line agent, despite a scarce evidence-base. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Brady L. Stein Source Type: research

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