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Survival Comparison Amongst Commonly Used Frontline Regimens in Patients Age 70 Years and Older with Acute Myeloid Leukemia (AML): A Single-Institution Study of Over 600 Patients
Optimal frontline therapy for elderly patients with AML remains controversial. In this large, single-institution retrospective cohort study of AML patients over age 70, we present survival analysis and comparison amongst a variety of commonly used regimens. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Varun Dhulipala, Martine Extermann, Najla Al Ali, Jongphil Kim, Marina Sehovic, Tea Reljic, Benjamin Djulbegovic, Jeffrey Lancet Source Type: research

Outcome of Allogeneic Hematopoietic Stem Cell Transplant in Therapy Related Myeloid Neoplasms: Comparative Study with a De Novo Myeloid Neoplasms Group
Therapy related myeloid neoplasms (t-MN) are associated with worse prognosis, resulting in a more complex therapeutic approach and a lack of an accepted standard therapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Oscar Ferre Bermejo, Estefania P érez, Oriana López-Godino, José María Bastida, Luis García-Martín, Felix López-Cadenas, Nerea Arratibel, Monica Baile, Alvaro Veiga, Dolores Caballero, Monica Cabrero Source Type: research

Relevance of Molecular Monitoring of Transcript Level in RUNX1-RUNX1T1 AML
Molecular breakpoint level fluctuations monitoring during AML treatment and subsequent follow-up may have role in prognosis and improve treatment decisions. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Larisa Girshova, Ekaterina Ovsyannikova, Konstantin Bogdanov, Sergey Kuzin, Andrey Zaritskey Source Type: research

Mutant NPM1 MRD and FLT3-ITD Status are Independent Prognostic Factors for the Risk of Relapse in AML Patients
Recent studies reported the prognostic relevance of measurable residual disease (MRD) after induction chemotherapy in AML patients with mutated NPM1 (mNPM1mrd). However, the predictive value of FLT3-internal tandem duplication (ITD) status at diagnosis in the context of mNPM1mrd remains controversial. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Tim Grob, Rosa Meijer, Fran çois Kavelaars, Mario Bargetzi, Carlos Graux, Markus Manz, Thomas Pabst, Jakob Passweg, Marie-Christiane Vekemans, Gert Ossenkoppele, Bob Löwenberg, Peter Valk, Mojca Jongen-Lavrencic Source Type: research

Up-Regulation of Regulatory T Cells, CD200 and TIM3 Expression in Acute Myeloid Leukemia (AML)
AML cells could evade immune control with AML microenvironment is immunosuppressive and anti-apoptotic favoring the survival of malignant hematopoietic cells. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Asmaa Zahran, Mona Sayed, Mostafa Mohammed Saleh Source Type: research

Prognostic Value of Regulatory T Cells, CD200 and TIM3 Expression in Acute Myeloid Leukemia (AML)
AML employ a number of immune evasion mechanisms which inhibit the generation or functional execution of anti-tumor immune responses that could contribute to disease resistance. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Asmaa Zahran, Mona Sayed, Mostafa Mohammed Saleh Source Type: research

5-year Experience of Oral Deferasirox (Exjade) Use Prior to Transplantation in Patients with Iron Overload that Underwent Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT): Retrospective Analysis of a Single Center from Turkey
Iron overload (IO) is considered an important cause of mortality and morbidity in patients who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). Iron chelation is critical in patients with IO prior to transplantation. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Serdar Sivgin, Esra Yildizhan, Neslihan Sanli, Leylagul Kaynar, Gokmen Zararsiz, Bulent Eser, Mustafa Cetin, Ali Unal Source Type: research

Dynamics of Molecular Response in AML Patients with NPM1 and FLT3 Mutations Undergoing Allogeneic Stem Cell Transplant
Concomitant NPM1 and FLT3 mutation occurs in 20% of AML patients. Molecular response and achievement of negative minimal residual disease (MRD) are strong predictors of long-term outcome. However, little is known about the dynamics of molecular response in NPM-1 and FLT-3 double positive mutations. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Rana Salem, Radwan Massoud, Rami Mahfouz, Ali Bazarbachi, Jean El Cheikh Source Type: research

Outcomes of Relapsed Core Binding Factor Acute Myeloid Leukemia: an MD Anderson Experience
CBF-AML, which accounts for ∼20% of AML, is defined by presence of t(8;21)(q22;q22) [t(8;21)] and inv(16)(p13q22) or t(16;16)(p13;q22) [inv(16)]. Although CBF-AML is considered a favorable cytogenetic subset, many patients experience relapse, and it is critical to identify features that can predict patient outcomes after rel apse. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Maliha Khan, Jorge Cortes, Wei Qiao, Mohanad Alzubaidi, Sherry Pierce, Rebacca Slack, Farhad Ravandi, Hagop Kantarjian, Gautam Borthakur Source Type: research

ARV-825, a BRD4 Inhibitor, Leads to Sustained Degradation of BRD4 with Broad Activity Against Acute Myeloid Leukemia and Overcomes Stroma Mediated Resistance by Modulating Chemokine Receptor, Cell Adhesion and Metabolic Targets
BRD4, a member of the bromodomain and extra terminal domain (BET) family, is critical in the assembly of a ‘super enhancer complex’ driving expression of oncogenes MYC, SOX2 and NF-KB and anti-apoptotic proteins e.g. Bcl-2 and BCL-XL and validated target in AML therapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Sujan Piya, Philip Lorenzi, Teresa McQueen, Eric Davis, Yimin Qian, Michael Andreeff, Gautam Borthakur Source Type: research

Gemtuzumab Ozogamicin Produces Durable Responses in Variant Acute Promyelocytic Leukemia with t(11;17)
We present two patients with t(11;17) APL successfully treated with GO. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Asha Balakrishnan, Kendra Sweet, Rami Komrokji, David Sallman, Eric Padron, Alan List, Jeffrey Lancet Source Type: research

Impact of Persistent Somatic Mutations on Day 14 After Induction Chemotherapy for Acute Myeloid Leukemia
Residual AML on D14 after induction typically warrants re-induction. This decision is based on D14 cellularity and blast count, yet many with aplastic D14 marrows fail to achieve CR. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Kendra Sweet, Mohammad Hussaini, Jeffrey Lancet, Rami Komrokji, Alan List, Lynn Moscinski, Jinming Song, Eric Padron Source Type: research

Andrographolide Pre-treatment Enhances the Anti-tumor Activity of Topotecan on Acute Myeloid Leukemia Cells In Vitro
Topotecan (TP) is an anticancer drug currently being used in the treatment of several cancer types including leukemia. However, due to its dose-limiting cytotoxicity, combination treatments have been investigated to achieve better outcome with less side effects. Andrographolide (AG) is a plant-derived compound that was reported to induce apoptosis and autophagy in acute myeloid leukemia cell lines. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Sandra Rizk, Sarah Abi Raad, Achraf Jardaly, Annalise Zouein, Paola Ghanem, Mohammad Hodroj Source Type: research

The Importance of CD200 in Differential Diagnosis of Chronic Lymphocytic Leukemia (CLL) and Possible Role of CD200 in Existence of Infection Complications
CLL is common hematological malignancy among Armenian population. 62 patients with the suspect of lymphoid neoplasm were admitted to Hematology Center of Armenia during last 2 years. The diagnosis was based on morphological, immunophenotyping, cytogenetic and FISH methods. All CLL cases had different clinical courses which were depend on clinical stage and accompanying infection complications. 32 of these patients had infection complications mainly in form of recurrent pneumonia. As the clinical features and phenotype of CLL are very similar to Mantle cell Lymphoma (MCL), CD200 was added to standard immunophenotyping panel...
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Aline Aywaz, Anna Sevoyan, Smbat Daghbashyan Source Type: research

Stimulation of the B-Cell Receptor (BCR) Induces Tyrosine Phosphorylation of STAT3 via NF- κB Dependent Mechanism
Whereas in CLL cells phosphorylation of STAT3 on serine 727 residues is constitutive, phosphorylation of STAT3 on tyrosine 705 residues is inducible. However, IL-6 induces tyrosine pSTAT3 phosphorylation within 15 minutes and IgM induces pSTAT3 within 2 to 4h. Like STAT3, the transcription factor NF- κB is constitutively activate in CLL cells. Because IL-6 is an NF-κB-target we wondered whether prolonged stimulation with IgM antibodies induces tyrosine pSTAT3 via NF-κB-mediated induction of IL-6 in CLL cells. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Uri Rozovski, David Harris, Ping Li, Zhiming Liu, Alessandra Ferrajoli, Burger Jan, Philip Thompson, William Wierda, Preetesh Jain, Michael Keating, Zeev Estrov Source Type: research

A 51 Year Old Man with Hypogammaglobulinemia Secondary to Chronic Lymphocytic Leukemia Receiving fSCIG in the Home Setting
We present a man with hypogammaglobulinemia secondary to CLL who received monthly fSCIG replacement treatments. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Michelle Greer, Leslie Vaughan, Elissa Ritt Source Type: research

Update on Efficacy and Tolerability of Ofatumumab as Front-Line Treatment for Patients with CLL that are Elderly and Have Severe Co-Morbidities and/or Other Malignancies
Elderly individuals with chronic lymphocytic leukemia (CLL) often present with multiple comorbidities and other cancers. Current therapy for these patients is largely based on targeted agents and/or monoclonal antibodies without chemotherapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Lorenzo Falchi, Candida Vitale, Maria Ciccone, Christina Hinojosa, Michael Keating, Naveen Pemmaraju, William Wierda, Gautham Borthakur, Jan Burger, Alessandra Ferrajoli Source Type: research

The CXCR4 Downstream Signaling Pathways in Chronic Lymphocytic Leukemia: a Target to Reverse Microenvironment Protection
Chronic lymphocytic leukemia (CLL) cells are protected from spontaneous and fludarabine-induced cell death by tumor microenvironment through the CXCL12/CXCR4 axis. The binding of CXCR4 to CXCL12 activates Ras/ERK1-2/Akt and RhoA-dependent signalling pathways. We have recently described the activation of Ras/ERK1-2 and RhoA/RhoA kinase signalling, the upregulation of the pro-survival factor Akt, and the increase in the activity of the transcription factor HIF-1 α in CLL cells co-cultured with stromal cells (SC). (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Candida Vitale, Valentina Griggio, Maria Todaro, Chiara Riganti, Iris Chiara Salaroglio, Chiara Salvetti, Micol Rigoni, Myriam Foglietta, Barbara Castella, Mario Bocacdoro, Massimo Massaia, Marta Coscia Source Type: research

Genetic Landscape and Gene Expression Profile of Chronic Lymphocytic Leukemia Patients with Ultra-Stable Disease
Chronic lymphocytic leukemia (CLL) shows a highly heterogeneous clinical course. Characterizing ultra-stable (US) CLL might help in elucidating the bases of CLL stability/progression. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Ilaria Del Giudice, Sara Raponi, Marilisa Marinelli, Jiguang Wang, Luciana Cafforio, Caterina Ilari, Monica Messina, Silvia Bonina, Simona Tavolaro, Mykola Bordyuh, Francesca Romana Mauro, Sabina Chiaretti, Davide Rossi, Gianluca Gaidano, Anna Guarini, Ra Source Type: research

Outcomes with Ibrutinib by Line of Therapy in Patients with CLL: Analyses from Phase 3 Data
Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the US FDA for the treatment of patients with CLL/small lymphocytic lymphoma, and allows for treatment without chemotherapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Nishitha Reddy, Susan O'Brien, John Byrd, Peter Hillmen, Steven Coutre, Jennifer Brown, Paul Barr, Jacqueline Barrientos, Stephen Devereux, Tadeusz Robak, Thomas Kipps, Alessandra Tedeschi, Florence Cymbalista, Paolo Ghia, Stephen Chang, Joi Ninomoto, Dan Source Type: research

Characteristics and Outcomes in Women and Men in the Connect ® CLL Registry
Previous studies prior to BCR-targeted agents suggest that women with chronic lymphocytic leukemia (CLL) have a more indolent clinical course, better responses to treatment, and improved survival than men. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Spencer Bachow, Chadi Nabhan, Anthony Mato, Christopher Flowers, Neil Kay, David Grinblatt, Matthew Davids, Mark Weiss, Kristen Sullivan, E. Dawn Flick, Pavel Kiselev, Shriya Bhushan, Arlene Swern, Jeff Sharman, Nicole Lamanna Source Type: research

A Phase 1 Clinical Trial of Cirmtuzumab, a First-in-Class ROR1 Inhibiting Antibody, for the Treatment of Patients with Relapsed or Refractory CLL: Interim Analysis
Malignant cells --but not normal cells-- from patients with chronic lymphocytic leukemia (CLL) and other cancers, have high expression of the oncoembryonic protein ROR1 (Receptor tyrosine kinase-like Orphan Receptor 1). Activation of ROR1 on CLL cells induces proliferation and migration via activation of downstream targets, including RhoA, Rac1, and Akt. Cirmtuzumab (UC-961) is a first-in-class monoclonal antibody designed to inhibit ROR1 signaling. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Michael Choi, Catriona Jamieson, George Widhopf, Jian Yu, Januario Castro, Reilly Kidwell, Hongying Li, Tiffany Juarez, Susette Gorak, Emily Pittman, Charlene Gutierrez, Laura Rassenti, Karen Messer, Charles Prussak, Thomas Kipps Source Type: research

Phase 3 Study of Ibrutinib versus Chlorambucil in Patients ≥65 Years with Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Alkylating agent chlorambucil has been commonly used for older patients with CLL/SLL, but novel therapies are needed. Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by US FDA for patients with CLL/SLL and allows for treatment without chemotherapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Jan Burger, Alessandra Tedeschi, Paul Barr, Tadeusz Robak, Carolyn Owen, Paolo Ghia, Osnat Bairey, Peter Hillmen, Nancy Bartlett, Jianyong Li, David Simpson, Sebastian Grosicki, Stephen Devereux, Helen McCarthy, Steven Coutre, Hang Quach, Gianluca Gaidano Source Type: research

Analysis of Quality of Life and Well-being from the Randomized Phase 3 Study of Ibrutinib Versus Chlorambucil in Older Patients with Treatment-na ïve CLL (RESONATE-2TM)
CLL is a disease primarily of older patients for whom quality of life (QOL) is an important consideration. Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the US FDA for the treatment of patients with CLL/small lymphocytic lymphoma and allows for treatment without chemotherapy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Thomas Kipps, Paolo Ghia, Alessandra Tedeschi, Paul Barr, Tadeusz Robak, Carolyn Owen, Osnat Bairey, Peter Hillmen, Nancy Bartlett, Jianyong Li, David Simpson, Sebastian Grosicki, Stephen Deverux, Helen McCarthy, Steven Coutre, Fritz Offner, Carol Moreno, Source Type: research

Prospective Evaluation of Safety and Efficacy of BR Regimen in Previously Untreated CLL Patients
Recently CLL10 trial showed remarkable efficacy and tolerability of BR regimen in highly selected previously untreated CLL patients. The way BR performs in “real-world” settings has not been evaluated in prospective manner. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Elena Stadnik, Vladimir Strugov, Tatyana Andreeva, Yulia Virts, Natalya Ilyina, Yulia Mirolubova, Pavel Butylin, Andrey Zaritskey Source Type: research

Targeting Ibrutinib-Resistant BTK-C481S Mutation with ARQ 531, a Reversible Non-Covalent Inhibitor of BTK
BTK, a key mediator of BCR signaling is a major target for ibrutinib. The acquired BTK-C481S mutation and oncogenic activation of PI3K/AKT signaling represent important resistant mechanisms. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Sudharshan Eathiraj, Ronald Savage, Yi Yu, Brian Schwartz, Jennifer Woyach, Amy Johnson, Sean Reiff, Giovanni Abbadessa Source Type: research

Phase I trial: CD19-Targeted CAR T-Cells in Patients with Residual CLL Following Initial Purine Analog-Based Therapy
Autologous T-cells genetically modified to express CD19-targeted 19-28z chimeric antigen receptors (CARs) induce clinically meaningful responses in a subset of patients with relapsed/refractory CLL. Greater disease burden at CAR T-cell infusion may limit efficacy. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Mark Geyer, Jae Park, Isabelle Rivi ère, Brigitte Senechal, Meier Hsu, Xiuyan Wang, Terence Purdon, Michel Sadelain, Renier Brentjens Source Type: research

A Dendritic Cell-Based Vaccine for CLL in Mice: Targeting the CDR3 Domain of B Cell Receptor
Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of mature B-cells in peripheral blood and lymphoid organs. 30% of patients can express BcR with structural similarity in the heavy chain complementarity-determining region 3 (BcR stereotypy). Several stereotyped subsets exist, each defined by a unique HCDR3 motif. Patients belonging to the same subset display similar clinical features. We preliminarily showed that synthetic peptides designed on the consensus sequence of stereotyped HCDR3 were immunogenic in vitro. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Alessandra Rovida, Tania Veliz Rodriguez, Francesca Gorini, Lydia Scarf ò, Cristina Maccalli, Paolo Dellabona, Paolo Ghia Source Type: research

Inhibition OF USP7 Induces Selective Cancer Cell Death in Chronic Lymphocytic Leukemia
CLL is a lymphoproliferative disorder with indolent clinical course. Beside standard chemoimmunotherapy, higher risk subgroups -namely those harboring TP53 mutations or deletions of the short arm of chromosome 17 (del17p)- may benefit from newer targeted drugs which act downstream of the B cell receptor. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Giovanna Carr à, Cristina Panuzzo, Davide Torti, Guido Parvis, Sabrina Crivellaro, Marco Volante, Deborah Morena, Marcello Lingua, Mara Brancaccio, Angelo Guerrasio, Pier Paolo Pandolfi, Giuseppe Saglio, Riccardo Taulli, Alessandro Morotti Source Type: research

Non-Oncogene Addiction to BRD in CLL: from JQ1 Response to Resistence
Despite significant advances in the molecular characterization of Chronic Lymphocytic Leukemia (CLL), CLL remains basically incurable and patients generally relapse after an initial response to standard care treatments, principally consisting in immuno-chemotherapy regimens. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Giovanna Carr à, Sabrina Crivellaro, Cristina Panuzzo, Deborah Morena, Marcello Lingua, Giuseppe Saglio, Riccardo Taulli, Alessandro Morotti Source Type: research

Venetoclax Plus Rituximab can Achieve Durable Treatment-Free Remission in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia
Venetoclax (VEN) is a selective, potent, orally bioavailable BCL-2 inhibitor. VEN in combination with rituximab (R) is being assessed in an ongoing Phase 1b study. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Michael Choi, Danielle Brander, Andrew W. Roberts, John F. Seymour, Thomas J. Kipps, Jacqueline C. Barrientos, Matthew S. Davids, Mary Ann Anderson, Constantine Tam, Betty Prine, Carmen Cornejo, Ming Zhu, Leanne Lash, Su Young Kim, Shuo Ma Source Type: research

Cross-Study Multivariable Analysis of the Impact of Adding Rituximab to Venetoclax on the Depth and Durability of Response in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia
Venetoclax (VEN) is a selective, potent, orally bioavailable BCL-2 inhibitor that induced high overall response rates (ORR, 79%) and complete responses (CR, 20%) in a first-in-human dose escalation study (M12-175) in patients with relapsed/refractory (R/R) CLL. The addition of monthly rituximab (R; months 1 –6) in combination with VEN is being evaluated in an ongoing phase 1b dose-escalation study (M13-365) and as of 28 Oct 2015, the observed ORR is 86% and the CR rate is 47%. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Constantine Tam, Andrew W. Roberts, Shuo Ma, Danielle Brander, Thomas J. Kipps, Jacqueline C. Barrientos, Matthew S. Davids, Mary Ann Anderson, Michael Choi, Leanne Lash, Maria Verdugo, Su Young Kim, Ming Zhu, John F. Seymour Source Type: research

Ventricular Arrhythmias and Sudden Death in Patients Taking Ibrutinib
Ibrutinib is a small molecule BTK inhibitor that has become a first- or second-line therapy for many patients with CLL and mantle cell lymphoma, but causes atrial fibrillation in approximately 6-9% of patients. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Benjamin Lampson, Lijian Yu, Jacqueline Barrientos, Eric Jacobsen, Versha Banerji, Jeffrey Jones, Kerry Savage, Renata Walewska, Javid Moslehi, Jennifer Brown Source Type: research

From Human Genetic to Mouse Model: SF3B1 Mutation and its Impact on Chronic Lymphocytic Leukemia
Large-scale sequencing studies using primary samples have identified SF3B1 as among the most frequently mutated genes in chronic lymphocytic leukemia (CLL). These mutations localize to a restricted gene region, with more than 50% at the K700E site. They co-occur at high frequency with ATM mutations and deletion of chromosome 11, whose minimally deleted region contains ATM. While SF3B1 mutations have been associated with adverse clinical outcome in CLL, mechanistic understanding of its role in the oncogenic phenotype is lacking. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Lili Wang, Angela Brooks, Rutendo Gambe, Jean Fan, Jing Sun, Sarah Hergert, Youzhong Wan, Donna Neuberg, Peter Kharchenko, Matthew Meyerson, Mark Fleming, Benjamin Ebert, Catherine Wu Source Type: research

Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in General Community: a Single-Center Experience
Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug which has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Naveed Ali, Syed Imran Mustafa Jafri, Faizan Malik, Mark Sundermeyer, Peter Pickens Source Type: research

Imatinib Mesylate as First-line Therapy in Patients with Chronic Myeloid Leukemia Philadelphia + (CML-PH+) in Accelerated Phase (AP), Comparison with Chronic Phase. A Long Term Retrospective Study
Accelerated phase (AP), is a progression state of CML. Treatment options varies; however in our institution, Imatinib Mesylate [(IM) Glivec ® Novartis, Mexico] is the only first line treatment avilable and the long-term outcome information is scarce in comparation with Chronic Phase (CP) CML (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Berenice Vicente-Hernandez, Rafael Hurtado-Monroy, Diego Sarre-Alvarez, Pablo Vargas-Viveros, Montserrat Rojas, Carlos Best, Judith Cruz-Vazquez, Myrna Candelaria-Hernandez Tags: Chronic Myelogenous Leukemia Source Type: research

Microsatellite Instability in Chronic Myeloid Leukemia Using D17S261 and D3S643 Markers- a Pilot Study in Western India
This study highlights the possibility of co-existence of microsatellite instability and chromosomal instability in samples with CML confirmed by t(9;22). (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Trupti Patel, Manali Chakraborty, Priyanjali Bhattacharya Source Type: research

Real-Life Discontinuation of TKIS
About 60% patients with CML in deep persistent molecular remission (MR4, MR4.5 or MR5), relapse after TKI discontinuation. Here we reported our real-life single center experience. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Debora Luzi Source Type: research

RT-qPCR and RT-Digital PCR: a Comparison of Different Platforms for the Evaluation of Residual Disease in Chronic Myeloid Leukaemia
Tyrosine Kinase Inhibitors (TKIs) are part of the successful clinical management of patients with Chronic Myeloid Leukaemia (CML). However, optimal clinical management of CML requires a robust, standardized laboratory assay used at key clinical milestones to ensure a successful outcome for patients on TKIs. Quantitative monitoring of %BCR-ABL1IS by reverse transcription quantitative PCR (RT-qPCR) is the gold standard strategy for evaluating patient repose to therapy and classification into prognostic subgroups. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Mary Alikian, Alexandra Whale, Susanna Akiki, Kim Piechocki, Celia Torrado, Thet Myint, Simon Cowen, Michael Griffiths, Jane Apperley, Helen White, Jim F. Huggett, Letizia Foroni Source Type: research

4-Year Results from the Pivotal Phase 2 PACE Trial: Efficacy and Safety in Heavily Pretreated Leukemia Patients
Ponatinib, an approved tyrosine kinase inhibitor, is potently active against native and resistant BCR-ABL, including BCR-ABL1T315I. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Jorge Cortes, Javier Pinilla-Ibarz, Philipp le Coutre, Ronald Paquette, Charles Chuah, Franck Nicolini, Jane Apperley, H. Jean Khoury, Moshe Talpaz, Michele Baccarani, Stephanie Lustgarten, Frank G. Haluska, Fran çois Guilhot, Michael W. Deininger, Andre Source Type: research

A Chart Review of Lower Dosing of Ponatinib in Patients with Chronic Myeloid Leukemia (CML): Preliminary Findings
Ponatinib is approved for adults with refractory CML or Ph+ ALL and those with the T315I mutation. Recommended starting dose is 45 mg/day. Post hoc dose-response analyses from the registrational PACE trial suggest lower doses may mitigate safety risk while maintaining response; outcomes with lower doses have not been evaluated in clinical practice. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Michael Mauro, Lisa McGarry, Ani Inguilizian, Ruth du Moulin, Hui Huang Source Type: research

The PACE Clinical Trial vs The Real-World: Comparison of Ponatinib Prescribing and Duration of Therapy in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients
The efficacy of ponatinib in refractory CP-CML was demonstrated in the pivotal phase 2 PACE trial (NCT01207440). Introduced in the US in December 2012, ponatinib was reintroduced in January 2014 after an 11-week withdrawal to review data on arterial occlusive events, revise US prescribing information, and institute a REMS program. In the US, ponatinib is exclusively distributed by Biologics, Inc., a specialty pharmacy that has maintained prescribing data since Jan 2014. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Michael Mauro, Lisa McGarry, Mo Yang, Stephanie Lustgarten, Hui Huang Source Type: research

Ponatinib versus Bosutinib in 3rd-Line Chronic Phase - Chronic Myeloid Leukemia (CP-CML): Indirect Comparison of Efficacy Using Iterative Proportional Fitting
Open-label trials of ponatinib (PACE, NCT01207440) and bosutinib (NCT00261846; published by Khoury 2012) in third-line patients with CP-CML suggest that ponatinib is more efficacious than bosutinib in this setting, but clinical and reimbursement decisions call for data from head-to-head trials. As such studies are unlikely, we indirectly compared efficacy in the two trials using Iterative Proportional Fitting (IPF) to adjust for differences in baseline characteristics. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Lisa McGarry, Mo Yang, Silvia Chiroli, Stephanie Lustgarten, David Dorer Source Type: research

The OPTIC Study: a Multi-Center, Randomized Phase 2 Trial with Response-Based Dose Reduction to Evaluate Three Starting Doses of Ponatinib
The initial approval of ponatinib (45 mg daily), a potent BCR-ABL tyrosine kinase inhibitor (TKI), for treatment of patients with refractory chronic myeloid leukemia (CML) or Philadelphia-positive acute lymphoblastic leukemia was based on the pivotal PACE trial (NCT01207440). Longer follow-up of PACE revealed a higher cumulative incidence of arterial occlusive events than originally reported at the time of approval. Modeling the data from PACE suggests that there is a dose-effect relationship with both adverse events (AEs) and response rates, and that lower doses may mitigate cardiovascular risk while maintaining efficacy....
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Valentin Garc ía Gutierrez, Jorge Cortes, Michael Deininger, Maria Baer, Vamsi Kota, Luke Akard, Charles Chuah, Agnes Guerci-Bresler, Juan Luis Steegmann, Juan-Carlos Hernández Boluda, Stephanie Lustgarten, Frank Haluska, Heinrich Farin Source Type: research

Detection of BCR-ABL Kinase Domain Mutations in Chronic Myeloid Leukemia Patients
The patient with chronic myeloid leukemia (CML) is treated successfully with tirosin kinase inhibitors (TKIs). Worldwide there are a 20 to 30% of patients, who have resistance to the treatment. The first cause of TKIs resistance is the presence of BCR-ABL kinase domain mutations. In Guatemalan population of around 35% of CML, patients are resistant to TKIs. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Nancy Escobar, Mariana Herrera, Luisa Rosales, Silvana Torselli, Julio Caceres, Mauricio Villegas, Mariela Guerra, Nely Marroquin, Claudia Osorio, Vanessa Zamora, Darwin Alvarez, Luis Alvarez, Claudia Carranza Source Type: research

OPTIC-2L: a Superiority Trial of Two Lower Doses of Ponatinib Versus Standard Dose Nilotinib in Second-Line Chronic Phase CML
Up to half of chronic-phase chronic myeloid leukemia (CP-CML) patients with first-line tyrosine kinase inhibitor (TKI) imatinib treatment become resistant or intolerant. A sizable portion of patients (38-49%) do not achieve major cytogenetic response (MCyR) with second-line treatment with dasatinib, nilotinib, or bosutinib. None of these agents have activity against all known kinase domain mutations and all are refractory to the T315I mutation. Ponatinib (45 mg daily), a potent pan-BCR-ABL TKI, demonstrated strong efficacy among a small cohort of second-line CP-CML patients, including those with the T315I mutation, in the ...
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Jeffrey Lipton, Andreas Hochhaus, Angelo Carella, Marianne Severinsen, Peter te Boekhorst, Antonio Almeida, Charles Chuah, Violaine Havelange, Gabriela Baerlocher, Stephanie Lustgarten, Heinrich Farin, Frank Haluska Source Type: research

Impact of Landmark Responses on 3-Year Outcomes in CP-CML Patients in the Ponatinib PACE Trial
Ponatinib is a potent oral tyrosine kinase inhibitor (TKI) approved for patients with refractory CML/Ph+ ALL, or with T315I. In first- and second-line settings with other TKIs, landmark responses have been correlated with positive long-term outcomes; data are limited for heavily pretreated populations. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Moshe Talpaz, Martin M üller, Michele Baccarani, Michael Deininger, François Guilhot, Andreas Hochhaus, Timothy Hughes, Neil Shah, Stephanie Lustgarten, Victor Rivera, Tim Clackson, Frank Haluska, Jorge Cortes Source Type: research

Dropled Digital PCR May Have a Prognostic Value for Predicting Relapse after Imatinib Discontinuation
Nowadays it is possible to safely discontinue imatinib but it is still not clear which patient (pt) will relapse. High sensitivity techniques like droplet digital (dd) PCR may help to discriminate pts who still present a significant amount of disease despite being in MR4 by standard RT-PCR. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Carmen Fava, Marta Varotto, Paola Berchialla, Enrico Gottardi, Filomena Daraio, Roberta Lorenzatti, Emilia Giugliano, Davide Barberio, Alessandra Iurlo, Ester Orlandi, Patrizia Pregno, Dario Ferrero, Giovanna Rege-Cambrin, Giuseppe Saglio Source Type: research

Rapid Achievement of MR4.5 after Switching from Imatinib to Nilotinib in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Preliminary Results from ENESTgoal
ENESTgoal is an ongoing phase 2 study of treatment-free remission (TFR) after second-line nilotinib in patients who achieved major molecular response (MMR) but not MR4.5 on imatinib. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Ellen Ritchie, Michael Deininger, Harry Erba, Michael Savona, Carole Paley, Ilva Dautaj, Michael Mauro Source Type: research

Inhibition of B-Catenin and Bcr-Abl Tyrosine Kinase Synergistically Targets Blast Crisis CML Cells and Stem/Progenitor Cells In Vitro and In Vivo
Bcr-Abl tyrosine kinase inhibitors (TKIs) have revolutionized CML treatment. However, these agents have limited activity against blast crisis (BC) CML, and are unable to eliminate leukemia stem cells. Interestingly, β-catenin, required for the maintenance of CML stem cells is constitutively activated in BC CML, which reputedly drives BC self-renewal capacity. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - August 26, 2016 Category: Hematology Authors: Bing Carter, Hongsheng Zhou, Po Mak, Hong Mu, Duncan Mak, Zhihong Zeng, Jorge Cortes, Michael Andreeff Source Type: research