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https://www.readbyqxmd.com/read/28721010/antiglioma-effects-of-cytarabine-on-leptomeningeal-metastasis-of-high-grade-glioma-by-targeting-the-pi3k-akt-mtor-pathway
#1
Kai-Hong Zhao, Can Zhang, Yue Bai, Yan Li, Xun Kang, Jian-Xin Chen, Kun Yao, Tao Jiang, Xiao-Song Zhong, Wen-Bin Li
Leptomeningeal metastasis (LM) of high-grade glioma is a highly lethal disease requiring new effective therapeutic measures. For both de novo or relapsed glioma with LM, intrathecal cytarabine chemotherapy is not frequently used for first-line and relapse protocols. We encountered a clinical case demonstrating effective application of cytarabine in high-grade glioma with LM, prompting us to explore the effects of cytarabine on malignant glioma and molecular mechanisms of such effects through in vivo and in vitro experiments...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28718728/a-phase-i-ii-randomized-trial-of-clofarabine-or-fludarabine-added-to-idarubicin-and-cytarabine-for-adults-with-relapsed-or-refractory-acute-myeloid-leukemia
#2
Nicholas J Short, Hagop Kantarjian, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M Kadia, William G Wierda, Courtney D DiNardo, Mark Brandt, Susan M O'Brien, Jorge E Cortes, Elias Jabbour
The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m(2) was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28717763/burkitt-s-lymphoma-and-b-cell-lymphoma-unclassifiable-with-features-intermediate-between-diffuse-large-b-cell-lymphoma-and-burkitt-s-lymphoma-in-patients-with-hiv-outcomes-in-a-south-african-public-hospital
#3
Gerhard Sissolak, Matthew Seftel, Thomas S Uldrick, Tonya M Esterhuizen, Nooroudien Mohamed, Danie Kotze
PURPOSE: Burkitt's lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. METHODS: We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28711923/acute-myeloid-leukemia-cells-require-6-phosphogluconate-dehydrogenase-for-cell-growth-and-nadph-dependent-metabolic-reprogramming
#4
Haymanti Bhanot, Ellen L Weisberg, Mamatha M Reddy, Atsushi Nonami, Donna Neuberg, Richard M Stone, Klaus Podar, Ravi Salgia, James D Griffin, Martin Sattler
Acute myeloid leukemia (AML) cells are highly dependent on glycolytic pathways to generate metabolic energy and support cell growth, hinting at specific, targetable vulnerabilities as potential novel targets for drug development. Elevated levels of NADPH, a central metabolic factor involved in redox reactions, are common in myeloid leukemia cells, but the significance or biochemical basis underlying this increase is unknown. Using a small molecule analog that efficiently inhibits NADPH-producing enzymes, we found that AML cells require NADPH homeostasis for cell growth...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708931/a-randomized-phase-2-study-of-idarubicin-and-cytarabine-with-clofarabine-or-fludarabine-in-patients-with-newly-diagnosed-acute-myeloid-leukemia
#5
Elias Jabbour, Nicholas J Short, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M Kadia, William G Wierda, Courtney D DiNardo, Mark Brandt, Susan M O'Brien, Jorge E Cortes, Hagop Kantarjian
BACKGROUND: Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS: Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients)...
July 14, 2017: Cancer
https://www.readbyqxmd.com/read/28703077/acute-myeloid-leukemia-during-pregnancy-a-systematic-review-and-meta-analysis
#6
Netanel A Horowitz, Israel Henig, Oryan Henig, Noam Benyamini, Liat Vidal, Irit Avivi
Data regarding clinical characteristics, therapy, maternal and fetal outcomes of pregnancy-associated acute myeloid leukemia (PA-AML) are limited. This study (including 138 cases published between 1955 and 2013) provides comprehensive assessment of these clinical parameters and may serve as a platform for developing management recommendations. Most patients (58%) received anthracycline-cytarabine-based regimens (ACBRs), which were associated with significantly increased complete remission (CR: 91%). Yet, the maternal overall survival (OS: ∼30%) was relatively low, probably reflecting reduced application of risk-adapted consolidation and allogeneic stem cell transplantation (allo-SCT)...
July 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28699673/combined-intravitreal-methotrexate-and-immunochemotherapy-followed-by-reduced-dose-whole-brain-radiotherapy-for-newly-diagnosed-b-cell-primary-intraocular-lymphoma
#7
Toshikatu Kaburaki, Kazuki Taoka, Junko Matsuda, Hideomi Yamashita, Izuru Matsuda, Hideki Tsuji, Rie Tanaka, Kumi Nakazaki, Fumihiko Nakamura, Kohei Kamiya, Mineo Kurokawa, Kuni Ohtomo, Makoto Aihara
Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy...
July 12, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28696028/pretransplant-functional-imaging-and-outcome-in-pediatric-patients-with-relapsed-refractory-hodgkin-lymphoma-undergoing-autologous-transplantation
#8
Nmazuo W Ozuah, Hisham M Dahmoush, Frederick D Grant, Leslie E Lehmann, Ann S LaCasce, Amy L Billett, Steven P Margossian
BACKGROUND: Pretransplant functional imaging (FI), particularly a negative positron emission tomography (PET), is a strong predictor of outcome in adults with relapsed or refractory Hodgkin lymphoma (HL), but data in pediatrics are limited. METHODS: The medical records of 49 consecutive pediatric patients, who received autologous transplant at a single institution, were retrospectively analyzed. All patients had either gallium or PET scan before transplant and were conditioned with carmustine, etoposide, cytarabine, and melphalan (BEAM)...
July 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28694633/facial-diplegia-as-initial-manifestation-of-acute-myelomonocytic-leukemia-with-isolated-trisomy-47-xy-11-14-46-xy-6
#9
Josef Finsterer, Michael Panny
Bilateral peripheral facial palsy (facial diplegia) has been repeatedly reported as a neurologic manifestation of acute myeloid leukemia but has not been reported as the initial clinical manifestation of myelomonocytic leukemia. A 71-year-old male developed left-sided peripheral facial palsy being interpreted and treated as Bell's palsy. C-reactive protein (CRP) and leukocyte count 4 days later were 2.5 mg/l and 16 G/l, respectively. Steroids were ineffective. Seven days after onset, he developed right-sided peripheral facial palsy...
July 2017: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/28693140/acute-myeloid-leukemia-with-t-3-21-q26-2-q22-developing-following-low-dose-methotrexate-therapy-for-rheumatoid-arthritis-and-expressing-two-aml1-mds1-evi1-fusion-proteins-a-case-report
#10
Keisuke Tanaka, Gaku Oshikawa, Hiroki Akiyama, Shinya Ishida, Toshikage Nagao, Masahide Yamamoto, Osamu Miura
The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)-ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687420/hepatic-adverse-event-profile-of-inotuzumab-ozogamicin-in-adult-patients-with-relapsed-or-refractory-acute-lymphoblastic-leukaemia-results-from-the-open-label-randomised-phase-3-ino-vate-study
#11
Hagop M Kantarjian, Daniel J DeAngelo, Anjali S Advani, Matthias Stelljes, Partow Kebriaei, Ryan D Cassaday, Akil A Merchant, Naohito Fujishima, Toshiki Uchida, Maria Calbacho, Anna A Ejduk, Susan M O'Brien, Elias J Jabbour, Hui Zhang, Barbara J Sleight, Erik R Vandendries, David I Marks
BACKGROUND: The INO-VATE study demonstrated efficacy and safety of inotuzumab ozogamicin versus standard care in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Here, we report the frequency of, and potential risk factors for, hepatotoxicity in patients in this trial and after treatment and subsequent haemopoietic stem-cell transplantation (HSCT). METHODS: In this open-label, phase 3, multicentre, international study, adults with relapsed or refractory, CD22-positive, Philadelphia chromosome (Ph)-positive or Ph-negative B-cell acute lymphoblastic leukaemia who were due to receive first or second salvage treatment were randomly assigned (1:1) via an interactive voice response system to receive inotuzumab ozogamicin (starting dose 1·8 mg/m(2) per cycle [0·8 mg/m(2) on day 1; 0·5 mg/m(2) on days 8 and 15 of a 21-28 day cycle for ≤6 cycles]) or standard care (either fludarabine plus cytarabine plus granulocyte colony-stimulating factor, mitoxantrone plus cytarabine, or high-dose cytarabine)...
July 4, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28684410/novel-mitochondrial-mechanisms-of-cytarabine-resistance-in-primary-aml-cells
#12
Aaron D Schimmer
Farge and colleagues describe a novel in vivo approach to identify and study primary acute myeloid leukemia (AML) cells that persist in the marrow after chemotherapy. They discovered that AML cells that persist in the mouse marrow after treatment with cytarabine have increased oxidative phosphorylation and that inhibiting oxidative phosphorylation can restore sensitivity to cytarabine. Cancer Discov; 7(7); 670-2. ©2017 AACR.See related article by Farge et al., p. 716.
July 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28682767/in-vitro-effects-of-purine-and-pyrimidine-analogues-on-leishmania-donovani-and-leishmania-infantum-promastigotes-and-intracellular-amastigotes
#13
Samira Azzouz, Philippe Lawton
Inhibition of parasite metabolic pathways is a rationale for new chemotherapeutic strategies. The pyrimidine and purine salvage pathways are thus targets against Leishmania donovani and L. infantum, causative agents of visceral human leishmaniasis and canine leishmaniosis. The antiproliferative effect of the pyrimidine analogues Cytarabine and 5-fluorouracil and of the purine analogues Azathioprine and 6-mercaptopurine was evaluated in vitro on the promastigote and the intracellular amastigote stages of the parasite...
September 26, 2017: Acta Parasitologica
https://www.readbyqxmd.com/read/28679736/cytarabine-dose-in-the-consolidation-treatment-of-aml-a-systematic-review-and-meta-analysis
#14
Kinkini N Magina, Gudrun Pregartner, Armin Zebisch, Albert Wölfler, Peter Neumeister, Hildegard T Greinix, Andrea Berghold, Heinz Sill
No abstract text is available yet for this article.
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28672876/novel-thiazolo-5-4-b-phenothiazine-derivatives-synthesis-structural-characterization-and-in-vitro-evaluation-of-antiproliferative-activity-against-human-leukaemia
#15
Balazs Brem, Emese Gal, Luiza Găină, Luminiţa Silaghi-Dumitrescu, Eva Fischer-Fodor, Ciprian Ionuţ Tomuleasa, Adriana Grozav, Valentin Zaharia, Lorena Filip, Castelia Cristea
The molecular frame of the reported series of new polyheterocyclic compounds was intended to combine the potent phenothiazine and benzothiazole pharmacophoric units. The synthetic strategy applied was based on oxidative cyclization of N-(phenothiazin-3-yl)-thioamides and it was validated by the preparation of new 2-alkyl- and 2-aryl-thiazolo[5,4-b]phenothiazine derivatives. Optical properties of the series were experimentally emphasized by UV-Vis absorption/emission spectroscopy and structural features were theoretically modelled using density functional theory (DFT)...
June 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28668386/rituximab-dose-dense-chemotherapy-with-or-without-high-dose-chemotherapy-plus-autologous-stem-cell-transplantation-in-high-risk-diffuse-large-b-cell-lymphoma-dlcl04-final-results-of-a-multicentre-open-label-randomised-controlled-phase-3-study
#16
Annalisa Chiappella, Maurizio Martelli, Emanuele Angelucci, Ercole Brusamolino, Andrea Evangelista, Angelo Michele Carella, Caterina Stelitano, Giuseppe Rossi, Monica Balzarotti, Francesco Merli, Gianluca Gaidano, Vincenzo Pavone, Luigi Rigacci, Francesco Zaja, Alfonso D'Arco, Nicola Cascavilla, Eleonora Russo, Alessia Castellino, Manuel Gotti, Angela Giovanna Congiu, Maria Giuseppina Cabras, Alessandra Tucci, Claudio Agostinelli, Giovannino Ciccone, Stefano A Pileri, Umberto Vitolo
BACKGROUND: The prognosis of young patients with diffuse large B-cell lymphoma at high risk (age-adjusted International Prognostic Index [aa-IPI] score 2 or 3) treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is poor. The aim of this study was to investigate the possible benefit of intensification with high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment in these patients. METHODS: We did a multicentre, open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design to compare, at two different R-CHOP dose levels, a full course of rituximab-dose-dense chemotherapy (no transplantation group) versus an abbreviated course of rituximab-dose-dense chemotherapy followed by consolidation with R-MAD (rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone) and high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) plus autologous stem-cell transplantation (transplantation group) in young patients (18-65 years) with untreated high-risk diffuse large B-cell lymphoma (aa-IPI score 2-3)...
June 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28666261/chemosensitivity-directed-therapy-compared-to-dacarbazine-in-chemo-naive-advanced-metastatic-melanoma-a-multicenter-randomized-phase-3-decog-trial
#17
Selma Ugurel, Carmen Loquai, Patrick Terheyden, Dirk Schadendorf, Erika Richtig, Jochen Utikal, Ralf Gutzmer, Knuth Rass, Cord Sunderkötter, Annette Stein, Michael Fluck, Martin Kaatz, Uwe Trefzer, Katharina Kähler, Rudolf Stadler, Carola Berking, Christoph Höller, Laura Kerschke, Lutz Edler, Annette Kopp-Schneider, Jürgen C Becker
Chemotherapy still plays an important role in metastatic melanoma, particularly for patients who are not suitable or have no access to highly efficacious new therapies. Pre-therapeutic chemosensitivity testing might be useful to identify optimal chemotherapy regimens for individual patients. This multicenter randomized phase-3 trial was aimed to test for superiority of chemosensitivity-directed combination chemotherapy compared to standard dacarbazine monochemotherapy, and to demonstrate the chemosensitivity test result as prognostic in metastatic melanoma...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28665999/analysis-of-the-role-of-intratecal-liposomal-cytarabine-in-the-prophylaxis-and-treatment-of-central-nervous-system-lymphomatosis-the-balearic-lymphoma-group-experience
#18
Marta García-Recio, Antonia Cladera, Leyre Bento, Julia Dominguez, Silvia Ruiz de Gracia, Francesca Sartori, Raquel Del Campo, Lucia García, Carmen Ballester, Jordi Gines, Joan Bargay, Antonia Sampol, Antonio Gutiérrez
Central nervous system (CNS) lymphomatosis is a fatal complication of aggressive non-Hodgkin lymphoma (NHL). In lymphoblastic or Burkitt lymphoma, without specific CNS prophylaxis the risk of CNS relapse is 20-30%. DLBCL has a lower risk of relapse (around 5%) but several factors increase its incidence. There is no consensus or trials to conclude which is the best CNS prophylaxis. Best results seem to be associated with the use of intravenous (iv) high-dose methotrexate (HDMTX) but with a significant toxicity...
2017: PloS One
https://www.readbyqxmd.com/read/28665351/specific-depletion-of-leukemic-stem-cells-can-micrornas-make-the-difference
#19
REVIEW
Tania Martiáñez Canales, David C de Leeuw, Eline Vermue, Gert J Ossenkoppele, Linda Smit
For over 40 years the standard treatment for acute myeloid leukemia (AML) patients has been a combination of chemotherapy consisting of cytarabine and an anthracycline such as daunorubicin. This standard treatment results in complete remission (CR) in the majority of AML patients. However, despite these high CR rates, only 30-40% (<60 years) and 10-20% (>60 years) of patients survive five years after diagnosis. The main cause of this treatment failure is insufficient eradication of a subpopulation of chemotherapy resistant leukemic cells with stem cell-like properties, often referred to as "leukemic stem cells" (LSCs)...
June 30, 2017: Cancers
https://www.readbyqxmd.com/read/28658145/central-hypothyroidism-in-a-pediatric-case-of-primary-acute-monoblastic-leukemia-with-central-nervous-system-infiltration-a-case-report
#20
Yuya Sato, Satomi Koyama, Shigeko Kuwashima, Masaya Kato, Mayuko Okuya, Keitaro Fukushima, Hidemitsu Kurosawa, Osamu Arisaka
RATIONALE: Central nervous system (CNS) leukemia is a frequent diagnosis in pediatric acute myeloblastic leukemia (AML) and includes neural symptoms. However, CNS leukemia is rarely associated with central hypsothyroidism. PATIENT CONCERNS AND DIAGNOSES: A 2-year-old female with AML with MLL rearrangement presented with CNS infiltration. Laboratory tests suggested the presence of central hypothyroidism (thyroid-stimulating hormone [TSH]: 0.48 mIU/ml, normal range 0...
June 2017: Medicine (Baltimore)
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