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high dose methotrexate

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https://www.readbyqxmd.com/read/28076839/chemotherapy-can-induce-weight-normalization-of-morbidly-obese-mice-despite-undiminished-ingestion-of-high-fat-diet
#1
Cheryl E Myers, Dominique B Hoelzinger, Tiffany N Truong, Lindsey A Chew, Arpita Myles, Leena Chaudhuri, Jan B Egan, Jun Liu, Sandra J Gendler, Peter A Cohen
Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074235/long-term-brain-structural-magnetic-resonance-imaging-and-cognitive-functioning-in-children-treated-for-acute-lymphoblastic-leukemia-with-high-dose-methotrexate-chemotherapy-alone-or-combined-with-cns-radiotherapy-at-reduced-total-dose-to-12%C3%A2-gy
#2
Olga Zając-Spychała, Mikołaj A Pawlak, Katarzyna Karmelita-Katulska, Jakub Pilarczyk, Katarzyna Derwich, Jacek Wachowiak
INTRODUCTION: The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. METHODS: Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment...
January 10, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28070711/immune-suppression-during-preclinical-drug-development-mitigates-immunogenicity-mediated-impact-on-therapeutic-exposure
#3
Jonathan Herskovitz, Josiah Ryman, Theingi Thway, Stephanie Lee, Lei Zhou, Narendra Chirmule, Bernd Meibohm, Vibha Jawa
In the clinical setting, anti-drug antibodies (ADA) against biotherapeutics can influence patient safety and interfere with product efficacy. High immunogenicity has been addressed in clinic by concomitant immune suppression, such as co-administration of methotrexate with enzyme replacement therapy (ERT) and combination tacrolimus/sirolimus treatment for prophylaxis against organ transplant rejection. This study investigates the use of such immune suppressants in mitigating ADA responses to a fully human monoclonal antibody (mAb1) in preclinical animal studies...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28060115/hepatotoxicity-during-maintenance-therapy-and-prognosis-in-children-with-acute-lymphoblastic-leukemia
#4
Maria S Ebbesen, Ulrikka Nygaard, Susanne Rosthøj, Ditte Sørensen, Jacob Nersting, Kim Vettenranta, Finn Wesenberg, Jon Kristinsson, Arja Harila-Saari, Kjeld Schmiegelow
Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine aminotransferases (ALAT) levels and relapse rate. We included 385 patients enrolled in the NOPHO ALL-92 protocol. Data on ALAT levels, 6 MP and MTX doses, cytotoxic MTX/6 MP metabolites, and thiopurine methyltransferase (TPMT) activity were prospectively registered...
January 5, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28035316/primary-pediatric-mid-brain-lymphoma-report-of-a-rare-pediatric-tumor-in-a-rare-location
#5
Rony Benson, Supriya Mallick, Suvendu Purkait, Vaishali Suri, K P Haresh, Subhash Gupta, Dayanand Sharma, Pramod Kumar Julka, Goura Kishore Rath
Primary central nervous system lymphoma (PCNSL) is a rare disease in pediatric age group. A thirteen-year-old male child presented with complaints of headache for six months, vomiting and diplopia for three days. Magnetic resonance imaging of the brain showed a single lesion of 1.7 cm × 1.6 cm × 1.6 cm in the mid brain and tectum. He underwent a gross total resection of the tumor. The histopathological evaluation revealed B cell high grade non Hodgkin lymphoma. The patient was treated with High dose methotrexate and cranio spinal radiation...
December 16, 2016: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28017209/high-dose-methotrexate-with-leucovorin-rescue-for-monumentally-severe-cns-inflammatory-syndromes
#6
Shin C Beh, Eric Kildebeck, Ram Narayan, Allen Desena, Doug Schell, Elizabeth S Rowe, Vernon Rowe, Dennis Burns, Louis Whitworth, Teresa C Frohman, Benjamin Greenberg, Elliot M Frohman
BACKGROUND: At sufficiently high doses, methotrexate (HDMTX) achieves substantial CNS penetration, whereas other tissues can be rescued from the effects of HDMTX by leucovorin rescue (LR), which does not penetrate the blood-brain barrier. OBJECTIVES: To report on the efficacy and safety of HDMTX with LR (HDMTX-LR), in the treatment of acute demyelinating inflammatory CNS syndromes refractory to conventional immunotherapy. METHODS: We performed a retrospective chart review of 12 patients treated (6 multiple sclerosis [MS], 4 neuromyelitis optica [NMO], and 2 Sjogren's syndrome myelopathy [SSM]) with HDMTX-LR after failing to improve, or exhibiting worsening following conventional immunotherapy...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28012564/an-intensified-dosing-schedule-of-subcutaneous-methotrexate-in-patients-with-moderate-to-severe-plaque-type-psoriasis-metop-a-52-week-multicentre-randomised-double-blind-placebo-controlled-phase-3-trial
#7
Richard B Warren, Ulrich Mrowietz, Ralph von Kiedrowski, Johannes Niesmann, Dagmar Wilsmann-Theis, Kamran Ghoreschi, Ina Zschocke, Thomas M Falk, Norbert Blödorn-Schlicht, Kristian Reich
BACKGROUND: Methotrexate is one of the most commonly used systemic drugs for the treatment of moderate to severe psoriasis; however, high-quality evidence for its use is sparse and limited to use of oral dosing. We aimed to assess the effect of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis. METHODS: We did this prospective, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (METOP) at 16 sites in Germany, France, the Netherlands, and the UK...
December 21, 2016: Lancet
https://www.readbyqxmd.com/read/28004435/biopsy-proven-case-of-epstein-barr-virus-ebv-associated-vasculitis-of-the-central-nervous-system
#8
Kohei Kano 鹿野耕平, Takayuki Katayama, Shiori Takeguchi, Asuka Asanome, Kae Takahashi, Tsukasa Saito, Jun Sawada, Masato Saito, Ryogo Anei, Kyousuke Kamada, Naoyuki Miyokawa, Hiroshi Nishihara, Naoyuki Hasebe
A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative...
December 22, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27992656/meta-regression-of-a-dose-response-relationship-of-methotrexate-in-mono-and-combination-therapy-in-dmard-naive-early-rheumatoid-arthritis-patients
#9
S A Bergstra, C F Allaart, T Stijnen, Rbm Landewé
OBJECTIVE: To investigate a possible short term dose-response relationship of initial treatment with methotrexate in monotherapy and combination therapy in recent onset rheumatoid arthritis (RA) patients. METHODS: A systematic literature search was performed on trials and cohorts including early, Disease Modifying Antirheumatic Drugs (DMARD) naive RA patients, treated with methotrexate, with data on clinical results within 6 months from treatment start. Cohen's effect sizes were calculated for the HAQ, ESR/CRP and/or DAS/DAS28 in 4 treatment groups: methotrexate monotherapy, or methotrexate in combination with synthetic (cs)DMARDs, biologic (b)DMARDs or glucocorticoids...
December 19, 2016: Arthritis Care & Research
https://www.readbyqxmd.com/read/27992063/rb-but-not-r-hcvad-is-a-feasible-induction-regimen-prior-to-auto-hct-in-frontline-mcl-results-of-swog-study-s1106
#10
Robert W Chen, Hongli Li, Steven H Bernstein, Samir Kahwash, Lisa M Rimsza, Stephen J Forman, Louis Constine, Thomas C Shea, Amanda F Cashen, Kristie A Blum, Timothy S Fenske, Paul M Barr, Tycel Phillips, Michael Leblanc, Richard I Fisher, Bruce D Cheson, Sonali M Smith, Malek Faham, Jennifer Wilkins, John P Leonard, Brad S Kahl, Jonathan W Friedberg
Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto-HCT) is effective for younger patients with mantle cell lymphoma (MCL). However, the optimal induction regimen is widely debated. The Southwestern Oncology Group S1106 trial was designed to assess rituximab plus hyperCVAD/MTX/ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) (RH) versus rituximab plus bendamustine (RB) in a randomized phase II trial to select a pre-transplant induction regimen for future development...
December 19, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27990383/biologics-use-in-indian-psoriasis-patients
#11
Murlidhar Rajagopalan, Asit Mital
The biologics currently in use for psoriasis in India are etanercept, infliximab and recently introduced itolizumab and secukinumab. Biosimilars, expected to play a significant role in psoriasis management in future, have also been available for the last few years. Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfill the eligibility criteria. The decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits...
November 2016: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/27987364/effect-of-the-polymorphism-of-folylpolyglutamate-synthetase-on-treatment-of-high-dose-methotrexate-in-pediatric-patients-with-acute-lymphocytic-leukemia
#12
Zhen Huang, Hong-Fei Tong, Yuan Li, Jiang-Chao Qian, Ju-Xiang Wang, Zhe Wang, Ji-Chen Ruan
BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. MATERIAL AND METHODS 57 ALL patients and 31 age and sex-matched children (control) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of the genotype of FPGS rs1544105 and high-performance liquid chromatography for measurement of MTX plasma concentration after 24-h and 44-h treatment...
December 17, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27966809/delayed-elimination-of-high-dose-methotrexate-and-use-of-carboxypeptidase-g2-in-pediatric-patients-during-treatment-for-acute-lymphoblastic-leukemia
#13
Thommy Svahn, Karin Mellgren, Arja Harila-Saari, Ann Åsberg, Jukka Kanerva, Ólafur Jónsson, Goda Vaitkeviciene, Torben Stamm Mikkelssen, Kjeld Schmiegelow, Jesper Heldrup
BACKGROUND: Carboxypeptidase G2 (CPDG2 ) can be used as rescue treatment in cases of delayed methotrexate elimination (DME) and Mtx-induced nephrotoxicity. PROCEDURE: Between July 2008 and December 2014, all children (1.0-17.9 years) in the Nordic countries diagnosed with Philadelphia chromosome negative acute lymphoblastic leukemia (ALL) were treated according to the Nordic Organization for Pediatric Hematology and Oncology (NOPHO) ALL 2008 protocol, including administration of six to eight high-dose (5 g/m(2) /24 hr) Mtx (HDMtx) courses...
December 14, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27964706/low-dose-methotrexate-ld-mtx-in-rheumatology-practice-a-most-widely-misunderstood-drug
#14
Anand N Malaviya
Methotrexate (MTX) was synthesised as a folate antagonist for use in treating childhood leukaemia in 1940s. Gubner and colleagues in 1953 used several log-order lower doses of MTX that mimicked the anti-inflammatory properties of cortisone. They used it successfully in treating rheumatoid arthritis (RA). Their work was however overlooked because the Nobel Prize winning drug cortisone held sway in those days. With increasing awareness of the adverse effects of cortisone, interest was rekindled in discovering 'steroid-sparing' drugs...
2016: Current Rheumatology Reviews
https://www.readbyqxmd.com/read/27941778/cytogenetics-and-outcome-of-allogeneic-transplantation-in-first-remission-of-acute-myeloid-leukemia-the-french-pediatric-experience
#15
A-L Alloin, G Leverger, J-H Dalle, C Galambrun, Y Bertrand, A Baruchel, A Auvrignon, V Gandemer, C Ragu, A Loundou, C Bilhou-Nabera, M Lafage-Pochitaloff, N Dastugue, B Nelken, C Jubert, F Rialland, G Plat, C Pochon, J-P Vannier, P-S Rohrlich, J Kanold, P Lutz, A Sirvent, C Oudin, W Cuccuini, G Michel
We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced...
December 12, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27941209/-subcutaneous-methotrexate-in-psoriasis-and-psoriatic-arthritis-treatment
#16
Aneta Szczerkowska-Dobosz
Methotrexate (MTX) plays a crucial role in the treatment of moderate-to-severe psoriasis. Thanks to numerous long-term observations and control clinical studies its safety and efficacy profile is well-established. Oral route of administration is the most common but data indicate the benefits of subcutaneous injections of MTX. Recent studies have revealed that bioavailability of oral MTX show interindividual differencies and decreases with the dose. In many cases to control disease activity MTX exceeding 15 mg/week is needed...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/27930548/primary-central-nervous-system-alk-positive-anaplastic-large-cell-lymphoma-in-an-adult-a-rare-case-report
#17
Xiaoqin Dong, Jun Li, Na Huo, Yan Wang, Zhao Wu, Xiaohong Lin, Hong Zhao
RATIONALE: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin lymphoma. It mostly invades lymph nodes with extranodal involvement observed in the soft tissue, bone, and skin. PATIENT CONCERNS: We report a 34-year-old Chinese male patient who presented with headache, diplopia, and vomit. Cerebrospinal fluid (CSF) analysis via lumbar puncture showed elevated CSF pressure, elevated CSF protein concentrations, decreased CSF glucose and chloride concentration significantly, and pleocytosis of 68 to 350 × 10/L, in which lymphocytes and monocytes were predominant...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27924163/highly-effective-auger-electron-therapy-in-an-orthotopic-glioblastoma-xenograft-model-using-convection-enhanced-delivery
#18
Helge Thisgaard, Bo Halle, Charlotte Aaberg-Jessen, Birgitte Brinkmann Olsen, Anne Sofie Nautrup Therkelsen, Johan Hygum Dam, Niels Langkjær, Sune Munthe, Kjell Någren, Poul Flemming Høilund-Carlsen, Bjarne Winther Kristensen
Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [(125)I]5-Iodo-2'-deoxyuridine ((125)I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED)...
2016: Theranostics
https://www.readbyqxmd.com/read/27908307/evolution-of-imaging-findings-laboratory-and-functional-parameters-in-rheumatoid-arthritis-patients-after-one-year-of-treatment-with-anti-tnf-%C3%AE-agents
#19
Efstathios E Detorakis, Eleftherios Magkanas, Ismini Lasithiotaki, Prodromos Sidiropoulos, Dimitrios T Boumpas, Nicholas Gourtsoyiannis, Katerina Antoniou, Maria Raissaki
OBJECTIVES: To investigate the efficacy and safety of anti-TNF-α agent treatment compared to non-biologic DMARDs in rheumatoid arthritis patients. METHODS: 82 consecutive patients, 29 males, 53 females, aged 42-79, diagnosed with RA and suitable for anti-TNF-α treatment composed two study groups: 42 with pre-existing rheumatoid arthritis-related interstitial lung disease (RA-ILD) and 40 without RA-ILD. Respective control groups consisted of 44 patients with pre-existing RA-ILD and 44 patients without RA-ILD, treated with non-biologic DMARDs...
October 27, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27888882/the-challenge-of-primary-central-nervous-system-lymphoma
#20
REVIEW
Julia Carnevale, James L Rubenstein
Primary central nervous system (CNS) lymphoma is a challenging subtypes of aggressive non-Hodgkin lymphoma. Emerging clinical data suggest that optimized outcomes are achieved with dose-intensive CNS-penetrant chemotherapy and avoiding whole brain radiotherapy. Anti-CD20 antibody-based immunotherapy as a component of high-dose methotrexate-based induction programs may contribute to improved outcomes. An accumulation of insights into the molecular and cellular basis of disease pathogenesis is providing a foundation for the generation of molecular tools to facilitate diagnosis as well as a roadmap for integration of targeted therapy within the developing therapeutic armamentarium for this challenging brain tumor...
December 2016: Hematology/oncology Clinics of North America
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