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high dose methotrexate

Hanne Kuitunen, Susanna Tokola, Topi Siniluoto, Matti Isokangas, Eila Sonkajärvi, Seppo Alahuhta, Taina Turpeenniemi-Hujanen, Esa Jantunen, Tapio Nousiainen, Kaija Vasala, Outi Kuittinen
Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation...
October 17, 2016: Journal of Neuro-oncology
A J Kivitz, S R Gutierrez-Ureña, J Poiley, M C Genovese, R Kristy, K Shay, X Wang, J P Garg, A Zubrzycka-Sienkiewicz
OBJECTIVE: To evaluate efficacy and safety of orally administered once-daily peficitinib in combination with methotrexate (MTX) in patients with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response to MTX. METHODS: In this multinational, phase IIb, randomized, double-blind, placebo-controlled, dose-ranging trial, patients with RA (N=378) were treated with peficitinib 25 mg, 50 mg, 100 mg, 150 mg + MTX, or matching placebo + MTX once daily for 12 weeks (NCT01554696)...
October 16, 2016: Arthritis & Rheumatology
Yueqin Han, Yanping Zhu, Jinshen Wang, Yanqin Han, Daogang Qin, Qiaozhi Yang, Xiaojing Sun, Lijun Chen
OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E)...
August 2016: Iranian Journal of Basic Medical Sciences
R Fleischmann, P J Mease, S Schwartzman, L-J Hwang, K Soma, C A Connell, L Takiya, E Bananis
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis investigated the effect of methotrexate (MTX) dose on the efficacy of tofacitinib in patients with RA. ORAL Scan (NCT00847613) was a 2-year, randomized, Phase 3 trial evaluating tofacitinib in MTX-inadequate responder (IR) patients with RA. Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo, with low (≤12.5 mg/week), moderate (>12.5 to <17.5 mg/week), or high (≥17...
October 12, 2016: Clinical Rheumatology
Yao Wang, Ping Huang, Minxi Hu, Wei Huang, Xinyuan Zhu, Deyue Yan
The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effectively. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio...
October 10, 2016: Bioconjugate Chemistry
Kentaro Inui, Tatsuya Koike
Strategies in rheumatoid arthritis (RA) based on 'treat to target' aim to control disease activity, minimize structural damage, and promote longer life. Several disease-modifying antirheumatic drugs (DMARDs) have been shown to be effective including biological DMARDs (bDMARDs). Treatment guidelines and recommendations for RA have also been published. According to those guidelines, conventional synthetic DMARDs (csDMARDs), as monotherapy or combination therapy, should be used in DMARD-naïve patients, irrespective of the addition of glucocorticoids (GCs)...
October 2016: Therapeutic Advances in Musculoskeletal Disease
Ankur Jain, Alka Khadwal, Gaurav Prakash, Nalini Gupta, Subhash Varma, Pankaj Malhotra
Testicular involvement in a case of acute lymphoblastic leukemia (ALL) is well reported, but occurrence of "isolated" malignant hydrocele is extremely uncommon. We herein report a case of a 22-year-old man who presented to our hematology clinic with fever and easy fatiguability of 2 weeks' duration. Examination revealed pallor, cervical lymphadenopathy, and bilateral scrotal swellings. He was diagnosed as a case of Philadelphia-positive ALL (B-cell type) based on peripheral smear, bone marrow examination, and flow cytometry of the marrow aspirate...
2016: Clinical Medicine Insights. Pathology
S Huang, L Jin, J Yang, Y L Duan, M Zhang, C J Zhou, Y H Zhang
Objective: To analyze the clinical features and outcomes of Burkitt lymphoma with testicular involvement and study the efficiency of high dose methotrexate (HD-MTX: 5-8g/m(2)) in those patients without radiation therapy. Method: Retrospective analysis was conducted in 16 Burkitt's lymphoma cases with testicular lymphoma involvement between Jan 2009 and Dec 2014. We followed the BCH-NHL-2009 protocol, modified from FAB LMB 89 combined with rituximab. All patients were enrolled in high-risk group (treated by Group C protocol)...
September 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Kenneth Carekin Kalunian, Mimi Kim, Xianhong Xie, Amrutha Baskaran, Rossi Paola Daly, Joan Tenenbaum Merrill
OBJECTIVE: Most clinical trials for systemic lupus erythematosus (SLE) study the efficacy and safety of investigational agents added to variable background immunosuppressants, which has resulted in high response rates in patients treated with placebo plus standard of care (SOC) plus rescue measures. This project compared the impact of different SOC treatments and disease variables on the outcomes of SLE trials. MATERIAL AND METHODS: Data were obtained from 981 patients receiving only SOC treatments in three nephritis and three general SLE trials to compare response and flare rates on the basis of the British Isles Lupus Assessment Group (BILAG) index, a measure common to all trials...
March 2016: Eur J Rheumatol
Jill J Hall, Monika Bolina, Trish Chatterley, Fakhreddin Jamali
OBJECTIVE: To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians. DATA SOURCES: A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs...
October 3, 2016: Annals of Pharmacotherapy
Aditi Khandelwal, Martina A Trinkaus, Hassan Ghaffar, Serge Jothy, Marc B Goldstein
BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare cause of proteinuria characterized by organized microtubular deposits in the glomerulus. ITG has been associated with underlying lymphoproliferative disorders and any renal impairment may be reversible with treatment of the concomitant hematologic malignancy. This case is the first reported in literature where diffuse large B cell lymphoma developed two years following the initial ITG diagnosis. CASE PRESENTATION: A 55-year-old woman with a history of well-controlled diabetes mellitus and thalassemia trait presented with proteinuria (830 mg/day) in 2010...
September 29, 2016: BMC Nephrology
Mihad Ibrahim, Rana Sabouni, Ghaleb A Husseini
Cancer is the uncontrolled growth of cells in the body and is considered as one of the major causes of death globally. There are several cytotoxic chemotherapeutic agents used to treat cancer including methotrexate, 5-fluorouracil, cisplatin, tamoxifen, doxorubicin and others. Although billions of dollars have been spent on cancer research to develop these chemotherapies, it still remains a major illness for mankind partly due to the shortcomings of these therapies. These shortcomings include low targeting specificity, severe side effects (due to high doses) and poor pharmacokinetics...
September 26, 2016: Current Medicinal Chemistry
Andrea Becciolini, Martina Biggioggero, Ennio Giulio Favalli
OBJECTIVE: In a real-life setting, to analyse retrospectively the effects of different methotrexate regimens on etanercept efficacy during the first year of treatment for rheumatoid arthritis (RA). METHODS: Demographic characteristics, clinical parameters and treatment data from patients with RA receiving the first-line biological disease-modifying antirheumatic drug, etanercept, as monotherapy or in combination with methotrexate were analysed at baseline and after 6 and 12 months...
September 2016: Journal of International Medical Research
Krishnan N Subrahmanian, Young H Shim, Mona D Shah, Brandon H Tran, Alexandra M Stevens, Andrea T Cruz
Emergency departments (EDs) are alert to the possibility of stroke and the need for early interventions to improve long-term clinical outcomes. However, new-onset hemiparesis in pediatric patients with leukemia may be due to a number of different etiologies, including most common side effects from chemotherapeutic agents. We present a case of a 15-year-old boy with pre-B acute lymphoblastic leukemia on chemotherapy, having recently received a high-dose methotrexate infusion in addition to intrathecal methotrexate therapy, who presented to our ED with acute right-sided hemiparesis...
September 23, 2016: Pediatric Emergency Care
Joel Correa da Rosa, Jaehwan Kim, Suyan Tian, Lewis E Tomalin, James G Krueger, Mayte Suárez-Fariñas
There is an 'assessment gap' between the moment patient treatment-response is biologically determined and when response can actually be determined clinically. Patients' biochemical profiles are a major determinant of clinical outcome for a given treatment. It is therefore feasible that molecular-level patient information could be used to decrease the assessment gap. Due to clinically accessible biopsies, high-quality molecular data for psoriasis patients is widely available. Psoriasis is therefore an excellent disease for testing the prospect of predicting treatment outcome from molecular data...
September 22, 2016: Journal of Investigative Dermatology
Mario Abinun, Jonathan P Lane, Mark Wood, Mark Friswell, Terence J Flood, Helen E Foster
Severe infections are emerging as major risk factors for death among children with juvenile idiopathic arthritis (JIA). In particular, children with refractory JIA treated with long-term, multiple, and often combined immunosuppressive and antiinflammatory agents, including the new biological disease-modifying antirheumatic drugs (DMARDs), are at increased risk for severe infections and death. We investigated 4 persons with JIA who died during 1994-2013, three of overwhelming central venous catheter-related bacterial sepsis caused by coagulase-negative Staphylococus or α-hemolytic Streptococcus infection and 1 of disseminated adenovirus and Epstein-Barr virus infection)...
October 2016: Emerging Infectious Diseases
Talha Munir, Mark J Bishton, Ian Carter, Andrew McMillan, Simon O'Connor, Vishakha Sovani, Andrew P Haynes, Christopher P Fox
INTRODUCTION: Large granular lymphocyte (LGL) leukemia is a rare chronic lymphoproliferative disorder, with few large series reported to date. Series using stringent diagnostic criteria incorporating bone marrow biopsy (BMB), immunophenotyping, and T-cell receptor rearrangements are even scarcer. PATIENTS AND METHODS: The present study was a single-center series of 39 patients with LGL leukemia diagnosed using immunohistochemical analysis of BMB samples and flow cytometric and molecular data...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
Yueqin Han, Yanping Zhu, Jinshen Wang, Yanqin Han, Daogang Qin, Qiaozhi Yang, Xiaojing Sun, Lijun Chen
OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E)...
July 2016: Iranian Journal of Basic Medical Sciences
Fabian Speth, Johannes-Peter Haas, Claas H Hinze
BACKGROUND: High-dose intravenous immune globulins (IVIg) are frequently used in refractory juvenile dermatomyositis (JDM) but are often poorly tolerated. High-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins (fSCIg) allow the administration of much higher doses of immune globulins than conventional subcutaneous immune globulin therapy and may be an alternative to IVIg. The safety and efficacy of fSCIg therapy in JDM is unknown. CASE PRESENTATION: In this retrospective case series, five patients with steroid-refractory severe JDM were treated with high-dose fSCIg due to IVIg adverse effects (severe headaches, nausea, vomiting, difficult venous access)...
2016: Pediatric Rheumatology Online Journal
H Rachadi, K Bouayad, S Chiheb
: Juvenile dermatomyositis (JDM) is a rare disease, with a mean age of onset of 7 years. We report a case of JDM in a 13-month-old infant. OBSERVATION: A 13-month-old infant presented with an edema of the upper lip, 4 days after receiving amoxicillin-clavulanate. The patient was treated with betamethasone and an antihistamine. Progression was marked by the appearance of a white edema of the periorbital area and the upper lip, with purpuric lesions, aphthoid ulcerations, and a drooping head...
October 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
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