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https://www.readbyqxmd.com/read/28818952/enasidenib-approved-for-aml-but-best-uses-unclear
#1
(no author information available yet)
The FDA approved the targeted therapy enasidenib for patients with refractory or relapsed acute myeloid leukemia with mutant IDH2 The drug produces remissions in some patients and may reduce the need for blood transfusions, although researchers acknowledge that the FDA's approval came with less supporting evidence than usual.
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28814980/cooperative-effect-of-chidamide-and-chemotherapeutic-drugs-induce-apoptosis-by-dna-damage-accumulation-and-repair-defects-in-acute-myeloid-leukemia-stem-and-progenitor-cells
#2
Yin Li, Yan Wang, Yong Zhou, Jie Li, Kai Chen, Leisi Zhang, Manman Deng, Suqi Deng, Peng Li, Bing Xu
BACKGROUND: Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which becomes the root of drug resistance and leukemia recurrence. A new strategy to eliminate LSCs in acute myeloid leukemia (AML) is therefore urgently needed. RESULTS: We report that a low-dose chidamide, a novel orally active benzamide-type histone deacetylase (HDAC) inhibitor, which selectively targets HDACs 1, 2, 3, and 10, could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine) in CD34(+)CD38(-) KG1α cells, CD34(+)CD38(-) Kasumi cells, and primary refractory or relapsed AML CD34(+) cells, reflected by the inhibition of cell proliferation, induction of apoptosis, and increase of cell cycle arrest in vitro...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28810561/cytotoxic-t-lymphocytes-promote-cytarabine-induced-acute-myeloid-leukemia-cell-apoptosis-via-inhibiting-bcl-2-expression
#3
Rui Deng, Fang-Yi Fan, Hai Yi, Li Fu, Yan Zeng, Yi Wang, Xiao-Juan Miao, Yan-Rong Shuai, Guang-Cui He, Yi Su
Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell-specific cytotoxic T lymphocytes (CTLs) in vitro and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte-depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3(+)CD8(+) CTLs through immune stimulation...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#4
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28804680/treatment-of-older-patients-with-acute-myeloid-leukemia-aml-revised-canadian-consensus-guidelines
#5
REVIEW
Joseph M Brandwein, Nancy Zhu, Rajat Kumar, Brian Leber, Mitchell Sabloff, Irwindeep Sandhu, Jeannine Kassis, Harold J Olney, Mohamed Elemary, Andre C Schuh
The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT)...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28804660/large-granular-lymphocytic-leukemia-a-report-of-response-to-rituximab
#6
Uroosa Ibrahim, Sara Parylo, Shiksha Kedia, Shafinaz Hussein, Jean Paul Atallah
Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28802867/novel-single-cell-technologies-in-acute-myeloid-leukemia-research
#7
REVIEW
Soumyasri Das Gupta, Zohar Sachs
Acute myeloid leukemia (AML) is a lethal malignancy because patients who initially respond to chemotherapy eventually relapse with treatment refractory disease. Relapse is caused by leukemia stem cells (LSCs) that reestablish the disease through self-renewal. Self-renewal is the ability of a stem cell to produce copies of itself and give rise to progeny cells. Therefore, therapeutic strategies eradicating LSCs are essential to prevent relapse and achieve long-term remission in AML. AML is a heterogeneous disease both at phenotypic and genotypic levels, and this heterogeneity extends to LSCs...
July 25, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28799432/targeted-therapies-in-acute-myeloid-leukemia-a-focus-on-flt-3-inhibitors-and-abt199
#8
Kiran Naqvi, Marina Konopleva, Farhad Ravandi
Acute myeloid leukemia (AML) remains a therapeutic challenge. Despite ongoing research, the standard therapy for AML has not changed significantly in the past four decades. With the identification of cytogenetic and molecular abnormalities, several promising therapeutic agents are currently being investigated. FLT3 mutation is a well-recognized target seen in 30% of the cytogenetically normal AML. More recently, the BCL2 family of anti-apoptotic proteins have also generated great interest as a therapeutic target...
August 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#9
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28794069/phase-i-study-of-the-anti-cd22-immunotoxin-moxetumomab-pasudotox-for-childhood-acute-lymphoblastic-leukemia
#10
Alan S Wayne, Nirali N Shah, Deepa Bhojwani, Lewis B Silverman, James A Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J Kreitman, Mark C Lanasa, Ira Pastan
Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter, phase I study was conducted to determine the maximum tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (n=55). Moxetumomab pasudotox was administered as a 30-minute intravenous infusion at doses of 5 to 50 µg/kg every other day (QOD) for six (Cohorts A and B) or 10 (Cohort C) doses, on 21-day cycles...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28792686/viral-surveillance-using-pcr-during-treatment-of-aml-and-all
#11
Stephanie B Dixon, Adam Lane, Maureen M O'Brien, Karen C Burns, Jennifer L Mangino, Erin H Breese, Michael J Absalon, John P Perentesis, Christine L Phillips
BACKGROUND: While viral surveillance of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus using PCR is routine in patients undergoing hematopoetic stem cell transplant and solid organ transplant, the utility in the nontransplant pediatric leukemia population is unknown. Our institution screens patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) for viral DNAemia by PCR as part of clinical care. PROCEDURE: This retrospective chart review included patients treated for newly diagnosed or relapsed AML or ALL between April 2010 and September 2014...
August 9, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28790849/immunotargeting-relapsed-or-refractory-precursor-b-cell-acute-lymphoblastic-leukemia-role-of-blinatumomab
#12
REVIEW
Manon Queudeville, Rupert Handgretinger, Martin Ebinger
Patients with refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) have a dismal prognosis of around 5% long-term survival when treated with cytotoxic chemotherapy and allogenic stem cell transplantation. T-cell immunobased strategies open up new therapeutic perspectives. Blinatumomab is the first of a new class of antibody constructs that was labeled bispecific T-cell engager (BiTE): it consists of two single chain variable fragment connected with a flexible linker, one side binding CD3, the other CD19...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790105/value-of-cytogenetic-abnormalities-in-adults-with-ph-negative-b-cell-precursor-acute-lymphoblastic-leukemia
#13
Marina Lafage-Pochitaloff, Laurence Baranger, Mathilde Hunault, Wendy Cuccuini, Christine Lefebvre, Audrey Bidet, Isabelle Tigaud, Virginie Eclache, Eric Delabesse, Chrystèle Bilhou-Nabéra, Christine Terré, Elise Chapiro, Nathalie Gachard, Marie-Joelle Mozziconacci, Geneviève Ameye, Sarah Porter, Nathalie Grardel, Marie C Béné, Yves Chalandon, Carlos Graux, Françoise Huguet, Véronique Lhéritier, Norbert Ifrah, Hervé Dombret
Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified GRAALL-2003/2005 trials. Combined data from karyotype, DNA index, FISH and/or PCR screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in ten exclusive primary cytogenetic subgroups and in secondary subgroups including complex and monosomal karyotypes...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#14
REVIEW
Michael Hallek
DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28780145/what-is-the-role-of-chemotherapy-in-patients-with-chronic-lymphocytic-leukemia
#15
REVIEW
Bruce D Cheson
The current standard treatment for patients with chronic lymphocytic leukemia who require therapy is chemoimmunotherapy. However, the availability of an increasing number of targeted agents and combination warrants a reassessment of that approach. The high rate of durable responses with ibrutinib in relapsed refractory patients has established its role in this setting; however, because of its impressive efficacy as initial treatment, it should be considered as part of the algorithm in appropriate patients. There is virtually no role for chemotherapy in the relapsed or refractory setting, but, instead, consideration of active agents including idelalisib plus rituximab, or, particularly venetoclax...
July 12, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28775119/incidence-and-management-of-toxicity-associated-with-ibrutinib-and-idelalisib-a-practical-approach
#16
Iris de Weerdt, Suzanne M Koopmans, Arnon P Kater, Michel van Gelder
The use of novel B cell receptor signaling inhibitors results in high response rates and long progression-free survival in patients with indolent B cell malignancies, such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and Waldenstroms macroglobulinemia. Ibrutinib, the first-in-class inhibitor or Bruton's tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ have recently been approved for several indolent B cell malignancies. These drugs especially foresee in previously unmet needs for patients with relapsed or refractory disease, high-risk cytogenetic or molecular abnormalities or with comorbidities...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28771903/fludarabine-cytarabine-g-csf-and-idarubicin-for-children-with-relapsed-aml
#17
Hideki Nakayama, Daisuke Tomizawa, Shiro Tanaka, Shotaro Iwamoto, Akira Shimada, Akiko M Saito, Yuka Yamashita, Hiroshi Moritake, Kiminori Terui, Takashi Taga, Hidemasa Matsuo, Yoshiyuki Kosaka, Katsuyoshi Koh, Hajime Hosoi, Hidemitsu Kurosawa, Keiichi Isoyama, Keizo Horibe, Shuki Mizutani, Souichi Adachi
BACKGROUND: The combination of fludarabine (Flu), high dose cytarabine (Ara-C) and granulocyte-colony stimulating factor (G-CSF) called "FLAG" with anthracyclines has become a standard chemotherapy for refractory acute myeloid leukemia (AML) in European children and adults. To clarify the efficacy and the safety of FLAG-idarubicin (IDA) for children prospectively, we planned a multicenter phase II study (AML-R11) by Japanese Pediatric Leukemia/Lymphoma Study Group. METHODS: Patients with AML at the age between 2 and 20 years old, who had the first bone marrow (BM) relapse or induction failure, were enrolled...
August 3, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28768111/providing-pediatric-palliative-care-education-using-problem-based-learning
#18
Karen Moody, Marlene McHugh, Rebecca Baker, Hillel Cohen, Priya Pinto, Stephanie Deutsch, Ruth O Santizo, Miriam Schechter, James Fausto, Pablo Joo
BACKGROUND: The Institute of Medicine and the American Academy of Pediatrics has called for improvement in education and training of pediatricians in pediatric palliative care (PPC). Given the shortage of PPC physicians and the immediate need for PPC medical education, this study reports the outcomes of a problem-based learning (PBL) module facilitated by academic general and subspecialty pediatric faculty (non-PPC specialists) to third year medical students. Objectives/Setting: To test the effectiveness of a PPC-PBL module on third year medical students' and pediatric faculty's declarative knowledge, attitudes toward, perceived exposure, and self-assessed competency in PPC objectives...
August 2, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28765140/clinical-development-of-car-t-cells-challenges-and-opportunities-in-translating-innovative-treatment-concepts
#19
REVIEW
Jessica Hartmann, Martina Schüßler-Lenz, Attilio Bondanza, Christian J Buchholz
Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities...
August 1, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28762313/adoptive-immunotherapy-for-b-cell-malignancies-using-cd19-targeted-chimeric-antigen-receptor-t-cells-a-systematic-review-of-efficacy-and-safety
#20
Lu Hao, Tongtong Li, Lung-Ji Chang, Xiaochuan Chen
BACKGROUND: Adoptive infusion of chimeric antigen receptor transduced T-cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results. OBJECTIVE: In this report, we performed a meta-analysis to evaluate the efficacy and side effects of CAR-T on relapsed B-cell malignancies, including leukemia and lymphoma. METHODS: Clinical studies investigating efficacy and safety of CAR-T in acute and chronic lymphocytic leukemia and lymphoma were identified by searching PubMed and EMBASE...
August 1, 2017: Current Medicinal Chemistry
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