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high dose methotrexate in acute leukemia

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https://www.readbyqxmd.com/read/28423235/hepatic-sinusoidal-obstruction-syndrome-during-maintenance-therapy-of-childhood-acute-lymphoblastic-leukemia-is-associated-with-continuous-asparaginase-therapy-and-mercaptopurine-metabolites
#1
Linea Natalie Toksvang, Silvia De Pietri, Stine N Nielsen, Jacob Nersting, Birgitte K Albertsen, Peder S Wehner, Steen Rosthøj, Päivi M Lähteenmäki, Daniel Nilsson, Tove A Nystad, Kathrine Grell, Thomas L Frandsen, Kjeld Schmiegelow
BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy...
April 19, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28413626/non-infectious-chemotherapy-associated-acute-toxicities-during-childhood-acute-lymphoblastic-leukemia-therapy
#2
REVIEW
Kjeld Schmiegelow, Klaus Müller, Signe Sloth Mogensen, Pernille Rudebeck Mogensen, Benjamin Ole Wolthers, Ulrik Kristoffer Stoltze, Ruta Tuckuviene, Thomas Frandsen
During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia...
2017: F1000Research
https://www.readbyqxmd.com/read/28338384/methotrexate-induced-neurotoxicity-in-hispanic-adolescents-with-high-risk-acute-leukemia-a-case-series
#3
Lisa Giordano, Oyinade Akinyede, Nidhi Bhatt, Dipti Dighe, Asneha Iqbal
Intrathecal methotrexate (IT MTX) and high-dose intravenous methotrexate (HD MTX) are important components of treatment in high-risk acute leukemia. We describe five Hispanic adolescents with high-risk acute leukemia at our institution who experienced MTX-induced neurotoxicity. All patients were eventually rechallenged with MTX. Two of the five patients had a second episode of neurotoxicity, but all patients recovered. Further studies should be performed to determine whether Hispanic patients are more susceptible to MTX neurotoxicity...
March 24, 2017: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/28285295/repeated-episodes-of-leukoencephalopathy-after-high-dose-methotrexate-in-a-child-with-acute-lymphoblastic-leukemia
#4
Teng-Fu Tsao, Yu-Hua Chao
No abstract text is available yet for this article.
February 15, 2017: Indian Pediatrics
https://www.readbyqxmd.com/read/28096535/genetics-of-ancestry-specific-risk-for-relapse-in-acute-lymphoblastic-leukemia
#5
S E Karol, E Larsen, C Cheng, X Cao, W Yang, L B Ramsey, C A Fernandez, J R McCorkle, S W Paugh, R J Autry, E Lopez-Lopez, B Diouf, S Jeha, C-H Pui, E A Raetz, N J Winick, W L Carroll, S P Hunger, M L Loh, M Devidas, W E Evans, J J Yang, M V Relling
The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single-nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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
#6
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...
February 2017: Neuroradiology
https://www.readbyqxmd.com/read/28060115/hepatotoxicity-during-maintenance-therapy-and-prognosis-in-children-with-acute-lymphoblastic-leukemia
#7
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...
April 2017: Journal of Pediatric Hematology/oncology
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
#8
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
#9
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/27941778/cytogenetics-and-outcome-of-allogeneic-transplantation-in-first-remission-of-acute-myeloid-leukemia-the-french-pediatric-experience
#10
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...
April 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27822085/danish-childhood-cancer-registry
#11
REVIEW
Henrik Schrøder, Catherine Rechnitzer, Peder Skov Wehner, Steen Rosthøj, Jens Kjølseth Møller, Birgitte Lausen, Gitte Petersen, Mette Nørgaard
AIM OF DATABASE: The overall aim is to monitor the quality of childhood cancer care in Denmark; to register late effects of treatment; to analyze complications of permanent central venous catheters (CVCs); to study blood stream infections in children with cancer; and to study acute toxicity of high-dose methotrexate infusions in children with leukemia. STUDY POPULATION: All children below 15 years of age at diagnosis living in Denmark diagnosed after January 1, 1985 according to the International Classification of Diseases 10, including diagnoses DC00-DD48...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27784356/-clinicopathologic-characteristics-and-outcome-of-isolated-ovarian-relapse-in-adolescent-with-acute-lymphoblastic-leukemia
#12
Ya-Ping Yu, Ping Song, Jian-Gang Mei, Zhi-Ming An, Xiao-Gang Zhou, Feng Li, Li-Ping Wang, Yu-Mei Tang, Yong-Ping Zhai
OBJECTIVE: To investigate the clinicopathologic characteristics,diagnosis and treatment of isolated ovarian relapse of acute lymphoblastic leukemia(ALL). METHODS: A 16-year-old girl presented with complaints of bone and joint pain. The peripheral blood and bone marrow(BM) smears showed 32% and 72% blasts, respectively, which were myeloperoxidase-negative. The blasts were positive for HLA-DR, TdT, CD10, CD19, CD22 and cCD79a and negative for CD34, CD5, CD7, CD13, CD33, CD56 and MPO detected by flow cytometry...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27721665/cytopathological-diagnosis-of-an-unusual-cause-of-malignant-hydrocele
#13
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
https://www.readbyqxmd.com/read/27668914/evaluation-and-management-of-acute-onset-hemiparesis-in-an-adolescent-with-leukemia
#14
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
https://www.readbyqxmd.com/read/27399166/influence-of-adora2a-gene-polymorphism-on-leukoencephalopathy-risk-in-mtx-treated-pediatric-patients-affected-by-hematological-malignancies
#15
Shin-Ichi Tsujimoto, Masakatsu Yanagimachi, Reo Tanoshima, Kevin Y Urayama, Fumiko Tanaka, Noriko Aida, Hiroaki Goto, Shuichi Ito
BACKGROUND: Methotrexate (MTX) can lead to neurotoxicity and asymptomatic leukoencephalopathy. However, the mechanism of MTX-related leukoencephalopathy is obscure. MTX and its metabolites inhibit 5-aminoimidazole-4-carboxamide ribonucleotide formiltransferase (ATIC) and promote adenosine release. Recently, it has been reported that adenosine and its receptor are related to certain central nervous system diseases. We investigated whether adenosine pathway gene polymorphisms and clinical factors were related to MTX-related leukoencephalopathy in pediatric patients affected by hematological malignancies...
November 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27384857/successful-high-dose-dexamethasone-treatment-of-acquired-pure-red-cell-aplasia-following-abo-major-mismatched-allogeneic-hematopoietic-stem-cell-transplantation
#16
REVIEW
Yuki Hiroshima, Yousuke Shiono, Ikuko Suzuki, Masakazu Yamamoto, Yuichi Kato, Katsushi Tajima, Takeo Kato
A 46-year-old man was diagnosed with acute myelomonocytic leukemia involving inv(16)(p13.1q22) in August 2007. He received a human leukocyte antigen-identical, ABO major-mismatched (donor: A, recipient: O) bone marrow transplantation from an unrelated donor in June 2009. Cyclosporin A (CsA) and short-course methotrexate were used for graft versus host disease prophylaxis. Although granulocyte and platelet engraftment were achieved, the patient exhibited persistent anemia and was dependent on red blood cell (RBC) transfusions...
June 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27249385/pharmacokinetik-population-of-methotrexate-in-tunisian-population-with-acute-lymphoblastic-leukemia
#17
Nadia Jebabli, Emna Gaïes, Hanen El Jebari, Rim Charfi, Mohamed Lakhal, Anis Klouz, Issam Salouage, Sameh Trabelsi
BACKGROUND: The use of high dose of MTX in the treatment of the leukemia is actually better controlled by renal preparation, control of plasma concentrations and administration of folinic acid. However, High dose MTX has been proven to cause substantial toxicity and have high intra-and inter-patient variability. Population pharmacokinetic analysis is a useful tool for identification of sources of pharmacokinetic variability during anticancer drug development and can aid the design of alternative dosing regimens to enhance their efficacy and safety...
December 2015: La Tunisie Médicale
https://www.readbyqxmd.com/read/27168705/effect-of-folate-status-and-methylenetetrahydrofolate-reductase-genotypes-on-the-complications-and-outcome-of-high-dose-methotrexate-chemotherapy-in-north-indian-children-with-acute-lymphoblastic-leukemia
#18
Nirmalya Roy Moulik, Archana Kumar, Suraksha Agrawal, Abbas Ali Mahdi, Ashutosh Kumar
PURPOSE: The genes of the folate metabolic pathway have been associated with toxicities during high dose methotrexate therapy for childhood ALL, however, the importance of intrinsic folate status in this regard is unclear. METHODS: In the present study the effect of precourse folate levels and MTHFR genotypes on the complications during high dose methotrexate chemotherapy in children with ALL were examined. RESULTS: Twenty-one children were studied...
April 2016: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/27121472/dasatinib-and-low-intensity-chemotherapy-in-elderly-patients-with-philadelphia-chromosome-positive-all
#19
Philippe Rousselot, Marie Magdelaine Coudé, Nicola Gokbuget, Carlo Gambacorti Passerini, Sandrine Hayette, Jean-Michel Cayuela, Françoise Huguet, Thibaut Leguay, Patrice Chevallier, Celia Salanoubat, Caroline Bonmati, Magda Alexis, Mathilde Hunault, Sylvie Glaisner, Philippe Agape, Christian Berthou, Eric Jourdan, José Fernandes, Laurent Sutton, Anne Banos, Oumedaly Reman, Bruno Lioure, Xavier Thomas, Norbert Ifrah, Marina Lafage-Pochitaloff, Anne Bornand, Laure Morisset, Valérie Robin, Heike Pfeifer, Andre Delannoy, Josep Ribera, Renato Bassan, Marc Delord, Dieter Hoelzer, Herve Dombret, Oliver G Ottmann
Prognosis of Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph(+) ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction...
August 11, 2016: Blood
https://www.readbyqxmd.com/read/27114587/dexamethasone-and-high-dose-methotrexate-improve-outcome-for-children-and-young-adults-with-high-risk-b-acute-lymphoblastic-leukemia-a-report-from-children-s-oncology-group-study-aall0232
#20
Eric C Larsen, Meenakshi Devidas, Si Chen, Wanda L Salzer, Elizabeth A Raetz, Mignon L Loh, Leonard A Mattano, Catherine Cole, Alisa Eicher, Maureen Haugan, Mark Sorenson, Nyla A Heerema, Andrew A Carroll, Julie M Gastier-Foster, Michael J Borowitz, Brent L Wood, Cheryl L Willman, Naomi J Winick, Stephen P Hunger, William L Carroll
PURPOSE: Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children's Oncology Group study AALL0232 tested two interventions to improve survival. PATIENTS AND METHODS: Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1...
July 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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