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Interim Report from a Phase 2 Multicenter Study of Tazemetostat, an EZH2 Inhibitor: Clinical Activity and Favorable Safety in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
New treatments with novel mechanisms of action are needed for patients with relapsed/refractory (R/R) DLBCL and FL. These tumor cells may depend on the histone methyltransferase EZH2 to perpetuate a less-differentiated state, and activating mutations may be oncogenic drivers. Tazemetostat, a potent, selective EZH2 inhibitor, shows antitumor activity in preclinical models and a phase 1 study in patients (pts) with mutated or wild-type (wt) EZH2 tumors. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Franck Morschhauser, Gilles Salles, Pamela McKay, Herv é Tilly, Anna Schmitt, John Gerecitano, Peter Johnson, Steven Le Gouill, Michael Dickinson, Christophe Fruchart, Thierry Lamy, Aristeidis Chaidos, Wojciech Jurczak, Stephen Opat, John Radford, Pier L Source Type: research

High-Risk Pregnancies Outcome in Women Treated With Low Molecular Heparin
Describing the incidence of some complications in high-risk pregnancies during which women were treated with Low Molecular Weight Heparin (LMWH) and their association with particular variables. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Georges Rameh, Fouad Kerbage, Elie Akoury, Anthony El Sabbagh, Mostapha Chaaban, Patrick Zaarour, Georges Chahine, Marcel Massoud Tags: Research Topics Source Type: research

A Novel High Throughput Process for Generation and Characterization of Chimeric Antigen Receptor (CAR) T Cells
T cells genetically engineered to express chimeric antigen receptors (CARs) bind to surface antigens via a single-chain variable fragment (scFv) and elicit potent anti-tumor activity. To our knowledge no rapid CAR development platforms exist to facilitate the high-throughput generation and characterization of novel CARs that allows comprehensive head-to-head comparisons and selection of the best CAR candidates for clinical development. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Sabarinath Venniyil Radhakrishnan, Adam Miles, Djordje Atanackovic, Tim Luetkens Source Type: research

Availability of Essential Medicines for Pediatric Oncology in Armenia
During recent decades substantial improvements has been documented in pediatric oncology and currently in high-income countries the survival of pediatric cancer is around 85%, however, the picture is totally different in low and middle income countries (LMIC), where around 80% of all pediatric cancer cases are documented: in LMIC pediatric cancer survival can range from 0 up to 50-60%. Among the others, one of the main challenges in LMIC is the availability of cancer medications. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Tamara Simonyan, Ruzanna Papyan, Lilit Sargsyan, Lusine Hakobyan, Varduhi Grigoryan, Hakob Topchyan, Arpina Azaryan, Armen Tananyan, Gevorg Tamamyan Source Type: research

CCR6, IL7R, FAS AND MAdCAM-1 Single Nucleotide Polymorphisms are Associated With Higher Incidence of Infections in Allogeneic Stem-Cell Transplant From a Related Donor After a Reduced Intensity Conditioning Regimen: A Multicenter Experience
Infection complications are important cause of morbidity and non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-SCT), even in HLA-identical sibling donors. Although there are many studies associating single nucleotide polymorphisms (SNPs) and allo-SCT evolution, these are mainly related with graft versus host disease (GVHD) and/or transplant related mortality (TRM), with few focused on post-allo-SCT infections. This multicentric study analyzes the potential implication of SNPs with cytomegalovirus (CMV) reactivation and fungal infection (FI) development in allo-SCT with reduced intensity c...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Nerea Arratibel, Maria Garc ía-Alvarez, Oriana Lopez-Godino, Estefania Garcia-Guerrero, Oscar Ferre, Eduardo Rodriguez-Arboli, Albert Esquirol, Cristina Castilla, Rodrigo Martino, Luis Corchete, Inmaculada Heras, Jose Antonio Perez-Simon, Estefanía Pere Source Type: research

Ruxolitinib for Steroid-Refractory GVHD
Steroid-refractory GVHD (SR-GVHD) is associated with poor outcomes and high rates of morbidity and mortality, and second-line agents have failed to demonstrate significant efficacy. A novel JAK1/2 inhibitor, ruxolitinib, which has been approved for subsets of myelofibrosis and polycythemia vera, has emerged as a possible therapeutic option in patients with SR-GVHD. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Alexander Coltoff, Guido Lancman, Amir Steinberg Source Type: research

Tandem High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Pediatric Brain Tumors
Central nervous system (CNS) tumors are the second most common pediatric malignancies with an about 25% 5-year overall survival rate in high-risk group. Children under 4 year have very bad prognosis. We tried to assess the effectiveness of tandem high-dose chemotherapy (HDCT) with autologous hematopoietic stem-cell transplantation (auto-HSCT) in this patient group. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Asmik Gevorgian, Elena Morozova, Ilya Kazantsev, Tatiana Iukhta, Svetlana Safonova, Yury Punanov, Ludmila Zubarovskaya, Olga Zheludkova, Boris Afanasyev Source Type: research

Distribution Chemotherapy Response Modulating Genetic Polymorphisms in Armenian Population
Primary chemotherapy drug resistance is a one of the major issues of medical hematology-oncology affecting about 20% of all patients. In Armenia, clinical data suggest that the rate of primary resistance depends on the disease and treatment type and varies in the range of 10-30%. One of the mechanisms of resistance is a drug inactivation mediated by metabolizing enzymes and it has been known that the variability of those genes contributes to the response to drugs and treatment efficacy. In Armenia a number of drugs are used for treatment acute and chronic hematology-oncological diseases, such as doxorubicin and vincristine...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Arsen Arakelyan, Yervand Hakobyan, Ani Melkonyan Source Type: research

Investigating the Mechanisms of Methotrexate Neurotoxicity in Patients With Childhood Leukemia and Long-Term Survivors
Adverse neurological events are common (4-20%) during treatment for pediatric acute lymphoblastic leukaemia (ALL) and include seizures, stroke like syndrome and leukoencephalopathy. In addition, chronic neurotoxicity is emerging as a worrying late effect of treatment with long-term survivors experiencing decreased executive function, processing speed and memory function. Survivors are also at increased risk of experiencing learning difficulties, social withdrawal issues and inattention hyperactivity disorders. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Victoria Forster, Jane Carr-Wilkinson, Deborah Tweddle, Sirintra Nakjang, Sanaa Choufani, Rosanna Weksberg, Frederik van Delft Source Type: research

Outcome of Neutropenic Fever in Hospitalized Cancer Patients During a One-Year Follow-up: A Single Center Experience
Febrile neutropenia is a relatively frequent event among cancer patients treated with chemotherapy. Since these patients lack the appropriate immunologic response, early recognition and empiric treatment is crucial. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Riwa Sakr, Marcel Massoud, Wafaa Greige, Nathalie Bteich, Layale Rached, Fadi Nasr, Elie Akoury, Fouad Kerbage, Georges Chahine Source Type: research

Development of a Prognostic System to Predict the Response to Treatment of Neutropenic Fever in Patients With Hematological Malignancies
Predicting the response to treatment for NF is critical in patients with hematological malignancy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Hamdy Zawam, Ahmad Selim, Rasha Salama, Nivin Hanna, Wael Edessa Source Type: research

Hematogones as a Prognostic Indicator in Allogeneic Hematopoietic Stem Cell Transplantation: Single Center Experience
Allogenic hematopoietic stem cell transplantation (aHSCT) is the treatment of choice for young severe aplastic anemia (SAA). Hematogones (HGs), reflect regeneration of bonemarrow post-chemotherapy and post-HSCT;a biomarker to predict aHSCT outcome. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Mai Aly, Douaa Sayed, Esam Elbeih, Rafaat Abdel Fattah, Refat Naseer, Reem Elagooz, Almetwaly M. Sultan, Nahla El-Sharkawy, Reda Z. Mahfouz Source Type: research

Allogeneic Hematopoietic Stem Cell Transplant in Elderly Patients Using Reduce Intensity Conditioning Regimen: A Single Centre Experience
Allogeneic stem cell transplantation (SCT) remains a cornerstone in the treatment strategy of most hematologic malignancies. Previously, age and comorbidities were considered limiting factors. With the introduction of reduced intensity conditioning regimens (RIC) and the understanding of donor immune function, allogeneic SCT in adults aged more than 60 years gained its place. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Riwa Sakr, Sylvain Pilorge, Stephane Debotton, Claude Chahine, Tereza Coman, David Ghez, Alina Danu, Micol Jean-Baptiste, Florence Pasquier, Vincent Ribrag, Christophe Willekens, Eric Solary, Jean-Henri Bourhis, Cristina Castilla-Llorente Source Type: research

Slow Lymphocyte Reconstitution After Autologous Stem Cell Transplantation is Associated with Increased Apoptosis Rate of CD8 Cells and Predicts Adverse Clinical Outcome
We noticed that in patients undergoing autologous stem cell transplantation (ASCT), the post-transplant lymphocyte counts fluctuated significantly during the first post-transplant weeks and wondered what is the clinical significance of this observation, and what dictates the lymphocyte counts overtime. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Uri Rozovski, Boris Tartakovsky, Shani Frank, Alexey Fourman, Eti Zigman-Hofman, Moshe Yeshurun, Svetlana Trestman, Ella Naparstek Source Type: research

Igvh Somatic Mutation Profile in Splenic Lymphomas: Opportunities for Differential Diagnosis
Splenic Lymphomas are rare diseases often misdiagnosed as hairy cell leukemia (HCL), splenic diffuse red pulp lymphoma (SDRPL) and splenic marginal zone lymphoma (SMZL). Criteria for differential diagnosis of these diseases are still controversial and require further elaboration. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Hunan Julhakyan, Bella Biderman, Lyubov Al-Radi, Igor Yakutik, Svetlana Korzhova, Alla Kovrigina, Andrey Sudarikov, Valeriy Savchenko Source Type: research

Eltrombopag and Cyclosporine as First-Line Therapy in Patients with Severe Acquired Aplastic Anemia: A Two-part, 5-year, Single-Arm, Multicenter, Open-label, Phase 2 Trial (SOAR)
Eltrombopag (EPAG), a thrombopoietin receptor agonist (TPO-RA), has shown promising results in severe aplastic anemia (SAA), as a single agent in immunosuppressive therapy (IST)-refractory patients and in treatment-na ïve patients when combined with horse antithymocyte globulin (hATG) and cyclosporine (CsA). hATG is unavailable in most parts of the world and is associated with increased toxicity, especially in patients aged>60 years. Moreover, ∼1/3rd of patients after ATG/CsA are considered refractory. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Phillip Scheinberg, Joan Maier, Ozlem Ocak Arikan, Carlo Finelli, Junho Jang Source Type: research

Sequential Regimen with Thiotepa, Cyclophosphamide, Etoposide, Fludarabine and Busulfan in Allogeneic Stem Cell Transplantation for the Treatment of Relapsed and Refractory Hematological Malignancies
Relapsed / refractory leukemia and lymphoma (R/R, L/L) patients have a very poor prognosis despite all the well-known therapeutic strategies. Sequential conditioning followed by allogeneic stem cell transplantation (allo-SCT) provides an efficient disease control in those high risk patients. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Haidar El Darsa, Radwan Massoud, Ammar Zahreddine, Ali Bazarbachi, Jean El-Cheikh Source Type: research

Repertoire of IgVH Genes in Splenic Marginal Zone Lymphoma Complicated with Autoimmune Hemolytic Anemia
Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoma frequently associated with monoclonal gammopathy and autoimmune disorders. Therefore, whereas it is well known that the prevalence of autoimmune hemolytic anemia (AIHA) is highest in the more advanced stages of the disease and may depend on the type of treatment administered. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Hunan Julhakyan, Bella Biderman, Nina Tsvetaeva, Lyubov Al-Radi, Tatyana Moiseeva, Tatyana Savenko, Elena Gribanova, Anait Melikyan, Andrey Sudarikov, Valeriy Savchenko Source Type: research

MGMT Promoter Methylation as an Epigenetic Biomarker for the Estimation of Chemosensitivity towards the Alkylating Agents Based Chemotherapies
The repair enzyme MGMT is recognized as having a provocative clinical relevance linked with cancerogenesis mechanisms and also with the chemosensitivity to particular oncological treatments including alkylating agents. Therefore, the analytical methods designed for the function of the gene encoding MGMT are actually developed in order to respond to specific needs, regarding diagnosis and predictive or prognostic approaches of treatments. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Natalia Cucu, V. Constantinescu, Lilia Matei, Mihaela Dragomir, Silvia Aposteanu, D. Coriu, Rodica Talmaci Source Type: research

The Opportunistic Pathogen Corynebacterium bovis Augments Leukemia Patient Derived Xenograft Engraftment: A Cautionary Tale
Chronic Myelomonocytic Leukemia (CMML) is a lethal hematopoietic malignancy with no available cell line, primary culture cells, or murine models that fully recapitulate the disease. We have recently reported that the NSG-S mouse model, which expresses human interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and stem cell factor (SCF) uniquely support the hematopoietic engraftment of human Chronic Myelomonocytic Leukemia (CMML) resulting in a humanized model that fully recapitulates the human condition (REF). (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Alexis Vedder, Emily Miedel, Natalie Ragland, Robert Engleman, Maria Balasis, Christopher Letson, Eric Padron Source Type: research

JC Virus and Progressive Multifocal Leukoencephalopathy After Haplo-Identical T-Cell Replete Transplantation with Post-Infusion Cyclophosphamide Recipient
Progressive multifocal leukoencephalopathy (PML), caused by reactivation of the John Cunningham virus (JCV), almost exclusively in immunocompromised patients, is a rare usually fatal disease. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Rana Salem, Radwan Massouud, Souha kanj Sharara, Manal Hamdan, Rida Salman, Ali Bazarbachi, Jean El Cheikh Source Type: research

Diagnostic and Therapeutic Limitations and Delayed Diagnosis of Pediatric Hematologic Malignancies in Armenia: A Single-Institution Report
There is a significant survival gap for pediatric hematologic malignancies between developed and developing countries, and various diagnostic and therapeutic limitations contribute for that. Diagnosis delay of pediatric malignancies is a challenge not only in developing, but also developed world, and the data on this topic is limited. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Liana Safaryan, Lilit Sargsyan, Lusine Hakobyan, Samvel Iskanyan, Armen Avagyan, Davit Zohrabyan, Lilit Harutyunyan, Samvel Bardakchyan, Sergey Mkhitaryan, Ruzanna Papyan, Jemma Arakelyan, Liana Avetisyan, Hovhannes Vardevanyan, Armen Tananyan, Gevorg Tam Source Type: research

CAR-T Enhancement by Combined TCR Knockdown and the RIAD Peptide Addition
Chimeric antigen receptor (CAR) is a recombinant fusion protein comprised of an antibody-derived targeting fragment and signaling domains capable to activate T cells. Ongoing clinical trials have demonstrated the remarkable ability of CAR-modified T cells to eliminate B cell malignancies. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Alexey Petukhov, Vitalia Markova, Pavel Gershovich, Alexey Titov, Evgeny Smirnov, Ekaterina Zaikova, Dmitry Motorin, Elena Petersen, Alexandr Karabelskii, Roman Ivanov, Andrey Zaritskey Source Type: research

Non-Covalent Conjugation of Antibodies and Lentiviruses to Nanoparticles as a Potential Tool for Gene Therapy
The use of chimeric antigen receptors (CARs) as well as CAR modfied cells is a very promising and effective therapeutic approach in current oncohematology. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Alexey Petukhov, Konstantin Shevchenko, Alexandra Daks, Tatyana Leonova, Alexey Titov, Evgeny Smirnov, Ekaterina Zaikova, Elena Petersen, Dmitry Motorin, Andrey Zaritskey, Maxim Nikitin Source Type: research

Role of Ddx41 in the Stimulator of Interferon Genes (STING) Pathway
Recently, an inherited predisposition to hematologic malignancies has been described in patients with heterozygous germ-line mutations in the pattern-recognition receptor DEAD-box polypeptide 41 (DDX41). The co-occurrence of immune disorders, suggests these mutations may result in defective immunologic sensing. DDX41 has been implicated as a critical component of the Stimulator of Interferon Genes (STING) pathway, which is required for the induction of spontaneous anti-tumor immune responses. Knockdown of DDX41 in vitro results in abrogated response to STING agonists, but whether DDX41 mutations affect STING pathway activi...
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Emily Curran, Jacob Mattingly, Lucy Godley, Justin Kline Source Type: research

Quality of Life Predictors in Patients with Dyspnea
Uncontrolled dyspnea is terrifying for patients and has a negative effect on quality of life (QOL) (Gupta, Lis,& Grutsch, 2007). Fatigue (92%), dyspnea (63%), and pain (55%) have been reported as the three most prevalent symptoms for patients diagnosed with higher risk myelodysplastic syndromes (MDS) (Efficace et al., 2015). Dyspnea and associated symptoms in advanced cancer are not adequately treated due to limited research and understanding of the experience (Twaddle et al., 2007). (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Sara Tinsley, Mayra Lee, Brent Small, Susan McMillan, Rami Komrokji Source Type: research

Implementing a Febrile Neutropenia Protocol: 3-year Follow-up Results
Current Febrile neutropenia (FN) guidelines recommend empiric use of cefepime or meropenem, sometimes combined with Vancomycin. Recently meta-analyses suggest this strategy may actually increase mortality. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 1, 2017 Category: Hematology Authors: Leonardo Gomes Teixeira Leite, Clarissa Cavalin Silva, Lara Ladislau Alves, Lisiana Wachholz Szeneszi, Priscila Carolina Almeida Fontes Guerra, Debora Cristina Malvar das Chagas, Elias Hallack Atta, Juliane Garcez Musacchio, Isabela Touma, Igor Gomes Clau Source Type: research

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