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high dose methotrexate in acute leukemia

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https://www.readbyqxmd.com/read/29922939/a-decrease-in-vitamin-d-levels-is-associated-with-methotrexate-induced-oral-mucositis-in-children-with-acute-lymphoblastic-leukemia
#1
N Oosterom, N F Dirks, S G Heil, R de Jonge, W J E Tissing, R Pieters, M M van den Heuvel-Eibrink, A C Heijboer, S M F Pluijm
PURPOSE: Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL...
June 19, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29911750/use-of-mthfr-c677t-polymorphism-and-plasma-pharmacokinetics-to-predict-methotrexate-toxicity-in-patients-with-acute-lymphoblastic-leukemia
#2
Lobna Ben Mahmoud, Moez Mdhaffar, Rim Frikha, Hanen Ghozzi, Ahmed Hakim, Zouheir Sahnoun, Moez Elloumi, Khaled Zeghal
BACKGROUND: Methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy, but it is associated with serious toxicities in a considerable number of patients. OBJECTIVES: The aim of the current study was to determine which variables were associated with MTX toxicity in children, adolescents and young adults with ALL. MATERIAL AND METHODS: In this prospective study, 35 patients with newly diagnosed ALL, treated according to the 58951 European Organization for Research and Treatment of Cancer - Children's Leukemia Group (EORTC-CLG) protocol, were prospectively enrolled...
June 18, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29790971/brain-activity-associated-with-attention-deficits-following-chemotherapy-for-childhood-acute-lymphoblastic-leukemia
#3
Slim Fellah, Yin T Cheung, Matthew A Scoggins, Ping Zou, Noah D Sabin, Ching-Hon Pui, Leslie L Robison, Melissa M Hudson, Robert J Ogg, Kevin R Krull
Background: The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. Methods: Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection...
May 21, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29768710/improving-the-safety-of-high-dose-methotrexate-for-children-with-hematologic-cancers-in-settings-without-access-to-mtx-levels-using-extended-hydration-and-additional-leucovorin
#4
Kalthi Vaishnavi, Deepak Bansal, Amita Trehan, Richa Jain, Savita Verma Attri
BACKGROUND: A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. METHODS: The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively...
May 16, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29759551/genomics-and-pharmacogenomics-of-pediatric-acute-lymphoblastic-leukemia
#5
REVIEW
Chuan Wu, Wei Li
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29672292/identification-of-risk-factors-in-high-dose-methotrexate-induced-acute-kidney-injury-in-childhood-acute-lymphoblastic-leukemia
#6
Dao-Hai Cheng, Hua Lu, Tao-Tao Liu, Xiao-Qin Zou, Hui-Mei Pang
AIMS: Although high-dose methotrexate (HDMTX) is an effective means for the treatment of acute lymphoblastic leukemia (ALL), the development of renal dysfunction remains a significant management challenge. This study aimed to identify the key factors in HDMTX-induced acute kidney injury (AKI) in childhood ALL. METHODS: We retrospectively analyzed the clinical data in 1,329 courses of HDMTX treatment in 336 Chinese ALL children at the First Affiliated Hospital of Guangxi Medical University from September 2012 to November 2016...
April 19, 2018: Chemotherapy
https://www.readbyqxmd.com/read/29596541/association-of-cerebrospinal-fluid-biomarkers-of-central-nervous-system-injury-with-neurocognitive-and-brain-imaging-outcomes-in-children-receiving-chemotherapy-for-acute-lymphoblastic-leukemia
#7
Yin Ting Cheung, Raja B Khan, Wei Liu, Tara M Brinkman, Michelle N Edelmann, Wilburn E Reddick, Deqing Pei, Angela Panoskaltsis-Mortari, Deokumar Srivastava, Cheng Cheng, Leslie L Robison, Melissa M Hudson, Ching-Hon Pui, Kevin R Krull
Importance: Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only. Objective: To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms. Design, Setting, and Participants: This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol...
March 29, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29484542/evolution-of-neurocognitive-function-in-long-term-survivors-of-childhood-acute-lymphoblastic-leukemia-treated-with-chemotherapy-only
#8
Wei Liu, Yin Ting Cheung, Heather M Conklin, Lisa M Jacola, DeoKumar Srivastava, Vikki G Nolan, Hongmei Zhang, James G Gurney, I-Chan Huang, Leslie L Robison, Ching-Hon Pui, Melissa M Hudson, Kevin R Krull
PURPOSE: The purpose of this study was to determine the evolution of neurocognitive problems from therapy completion to long-term follow-up in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. METHODS: We evaluated whether attention problems observed at therapy completion evolve into long-term executive dysfunction in 158 survivors treated on a single institution protocol. Treatment data (high-dose intravenous methotrexate exposure [serum concentration] and triple intrathecal chemotherapy injections) were collected...
February 27, 2018: Journal of Cancer Survivorship: Research and Practice
https://www.readbyqxmd.com/read/29424258/anti-leukemic-treatment-induced-neurotoxicity-in-long-term-survivors-of-childhood-acute-lymphoblastic-leukemia-impact-of-reduced-central-nervous-system-radiotherapy-and-intermediate-to-high-dose-methotrexate
#9
Olga Zając-Spychała, Mikolaj Pawlak, Katarzyna Karmelita-Katulska, Jakub Pilarczyk, Katarzyna Jończyk-Potoczna, Agnieszka Przepióra, Katarzyna Derwich, Jacek Wachowiak
The aim of the study was to evaluate the long-term neurodevelopmental consequences of currently applied acute lymphoblastic leukemia (ALL) therapy containing chemotherapy alone or combined with 12 Gy radiotherapy. Seventy-nine children aged 6.3-21.7 years diagnosed with ALL and treated according to ALL IC-BFM 2002 have been studied. The control group consisted of 23 children newly diagnosed with ALL. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between three therapeutic schemes and patients prior to treatment...
February 9, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29412158/allogeneic-hematopoietic-stem-cell-transplantation-for-gata2-deficiency-using-a-busulfan-based-regimen
#10
Mark Parta, Nirali N Shah, Kristin Baird, Hind Rafei, Katherine R Calvo, Thomas Hughes, Kristen Cole, Meg Kenyon, Bazetta Blacklock Schuver, Jennifer Cuellar-Rodriguez, Christa S Zerbe, Steven M Holland, Dennis D Hickstein
Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients...
February 3, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29383863/effectiveness-of-modified-hyper-cvad-chemotherapy-regimen-in-the-treatment-of-adult-acute-lymphoblastic-leukemia-a-retrospective-experience
#11
Hasan Jalaeikhoo, Mohsen Rajaeinejad, Manoutchehr Keyhani, Mohammad Zokaasadi, Mohammad Mehdi Dehghani Firoozabadi
Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long-term survival. The hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper-CVAD protocol...
March 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29328996/acute-and-sub-acute-neurological-toxicity-in-children-treated-for-acute-lymphoblastic-leukemia
#12
REVIEW
Natalia C Millan, Analía Pastrana, Myriam R Guitter, Pedro A Zubizarreta, María S Monges, María S Felice
Eighty percent of children with acute lymphoblastic leukemia (ALL) survive with current treatments. Neurotoxicity is an infrequent adverse event. We describe clinical presentations of neurological toxicity, phases of treatment when these adverse events were more frequent and patients ́ outcome. From January-1995 to December-2015, 1379 ALL cases were admitted. Neurotoxicity was diagnosed in 49 patients (3.6%) and classified according to neurological syndromes. Medical records, laboratory-tests and images were reviewed...
February 2018: Leukemia Research
https://www.readbyqxmd.com/read/29286562/isolated-late-testicular-relapse-of-b-cell-acute-lymphoblastic-leukemia-treated-with-intensive-systemic-chemotherapy-and-response-based-testicular-radiation-a-children-s-oncology-group-study
#13
Julio C Barredo, Caroline Hastings, Xiamin Lu, Meenakshi Devidas, Yichen Chen, Daniel Armstrong, Naomi Winick, Brent Lee Wood, Rochelle Yanofsky, Mignon Loh, Julie M Gastier-Foster, Dean Thomas Jorstad, Robert Marcus, Kim Ritchey, William L Carrol, Stephen P Hunger
BACKGROUND: The incidence of isolated testicular relapse (ITR) of acute lymphoblastic leukemia (ALL) has decreased with contemporary treatment strategies, but outcomes are suboptimal with a 58% 5-year overall survival (OS). This study aimed to improve outcome in patients with ITR of B-cell ALL (B-ALL) occurring after 18 months of first clinical remission using intensive systemic chemotherapy and to decrease long-term sequelae by limiting use of testicular radiation. PROCEDURE: Forty patients in first ITR of B-ALL were enrolled...
May 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29274118/cost-comparison-by-treatment-arm-and-center-level-variations-in-cost-and-inpatient-days-on-the-phase-iii-high-risk-b-acute-lymphoblastic-leukemia-trial-aall0232
#14
Amanda M DiNofia, Alix E Seif, Meenakshi Devidas, Yimei Li, Matthew Hall, Yuan-Shung V Huang, Viviane Cahen, Stephen P Hunger, Naomi J Winick, William L Carroll, Brian T Fisher, Eric C Larsen, Richard Aplenc
The Children's Oncology Group (COG) develops and implements multi-institutional clinical trials with the primary goal of assessing the efficacy and safety profile of treatment regimens for various pediatric cancers. However, the monetary costs of treatment regimens are not measured. AALL0232 was a COG randomized phase III trial for children with acute lymphoblastic leukemia that found that dexamethasone (DEX) was a more effective glucocorticoid than prednisone (PRED) in patients younger than 10 years, but PRED was equally effective and less toxic in older patients...
January 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29210328/dna-variants-in-dhfr-gene-and-response-to-treatment-in-children-with-childhood-b-all-revisited-in-aieop-bfm-protocol
#15
Francesco Ceppi, Vincent Gagné, Laurance Douyon, Camille J Quintin, Antonella Colombini, Rosanna Parasole, Barbara Buldini, Giuseppe Basso, Valentino Conter, Giovanni Cazzaniga, Maja Krajinovic
AIM: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. METHODS: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome...
January 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29146215/-acute-methotrexate-related-neurotoxicity-and-pseudo-stroke-syndrome
#16
V Deneux, N Leboucq, L Saumet, S Haouy, T Akbaraly, N Sirvent
Treatment of acute lymphoblastic leukemia requires high-dose systemic and/or intrathecal methotrexate to prevent and/or treat central nervous system disorders. Acute neurotoxicity of methotrexate, of unknown etiopathogenesis, is characterized by the polymorphism of clinical manifestations, responsible for a potentially harmful diagnostic delay in these immunosuppressed patients. We describe five episodes of transient acute leukoencephalopathy mimicking a stroke, reported in the literature as "pseudo-stroke syndrome"...
December 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29143423/treatment-and-biology-of-pediatric-acute-lymphoblastic-leukemia
#17
REVIEW
Motohiro Kato, Atsushi Manabe
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In the past ALL was intractable but now the survival probability is as high as 80-90%. Improved supportive care, treatment stratification based on relapse risk, biological features of leukemic cells, and optimization of treatment regimens by nationwide and international collaboration have contributed to this dramatic improvement. While including traditional risk factors (e.g. age and leukocyte count at diagnosis), the treatment has been modified based on biological characteristics (aneuploidy and translocation) and treatment response (assessed by minimal residual disease)...
January 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29120974/plasma-7-hydroxymethotrexate-levels-versus-methotrexate-to-predict-delayed-elimination-in-children-receiving-high-dose-methotrexate
#18
Nicolas Fabresse, Bénédicte Devictor, Christel Pissier, Hervé Chambost, Bruno Lacarelle, Gérard Michel, Caroline Solas
BACKGROUND: The aim of this study was to investigate the correlation between 7-hydroxymethotrexate (7-OHMTX) and creatinine and to evaluate the predictive value of 7-OHMTX levels on delayed elimination at 24 and 48 hours. In addition, differences in methotrexate (MTX), 7-OHMTX levels, and MTX metabolism using the ratio MTX/7-OHMTX were determined according to age. METHODS: The authors included a total of 106 cycles, corresponding to 33 patients (mean age: 9.8 years, range: 2-18 years) suffering from acute lymphoblastic leukemia, non-Hodgkin lymphoma and osteosarcoma and receiving high-dose MTX (HD-MTX)...
February 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29050116/-correlation-study-of-blood-drug-concentration-and-nephrotoxicity-on-high-dose-methotrexate-therapy-in-suggestion-of-diagnosis-and-treatment-of-childhood-acute-lymphoblastic-leukemia-in-the-4th-revised-edition
#19
D H Cheng, H Lu, X Q Zou
Objective: To explore the influence of the 4th revised treatment recommendations in childhood acute lymphoblastic leukemia (ALL) on high dose methotrexate(HD-MTX)-induced nephrotoxicity and MTX blood concentrations. Method: The clinical data from 330 ALL children who received 1 242 courses of HD-MTX therapies from September 2012 to November 2016 was collected. The courses were divided into two groups based on the chemotherapies: original scheme group was treated with the 3rd revised regimen, and new scheme group was treated with the 4th revised regimen...
October 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29047158/hyper-cvad-plus-nelarabine-in-newly-diagnosed-adult-t-cell-acute-lymphoblastic-leukemia-and-t-lymphoblastic-lymphoma
#20
Yasmin Abaza, Hagop M Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days...
January 2018: American Journal of Hematology
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