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high dose methotrexate in acute leukemia

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
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
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
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
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
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
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
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
Burcu Yazıcıoğlu, Zühre Kaya, Sezen Güntekin Ergün, Ferda Perçin, Ülker Koçak, İdil Yenicesu, Türkiz Gürsel
OBJECTIVE: High-dose methotrexate (HD-MTX) is widely used in the consolidation phase of childhood acute lymphoblastic leukemia (ALL), but the roles that polymorphisms in folate-related genes (FRG) play in HD-MTX toxicity and prognosis in children with ALL are not well known. The aims of this study were to i) investigate the frequencies of polymorphisms in the genes for thymidilate synthase (TS), methionine synthase reductase (MTRR), and methylene tetrahydrofolate reductase (MTHFR) in Turkish children with ALL, and ii) assess for associations between these polymorphisms and HD-MTX-related toxicity and leukemia prognosis in this patient group...
April 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Maurizio Lucchesi, Milena Guidi, Carla Fonte, Silvia Farina, Patrizio Fiorini, Claudio Favre, Maurizio de Martino, Iacopo Sardi
PURPOSE: In infants aged less than 12 months, there are few data on pharmacokinetics of high-dose methotrexate (MTX) for brain tumors at the dose of 8 g/m(2). Consolidated knowledges are present only with the dose of 5 g/m(2) in acute lymphoblastic leukemia. METHODS: We collected data on 8 infants at the time of their first treatment with high-dose MTX, 8 g/m(2), to evaluate the pharmacokinetic profile. All children had a dose adjustment with a weight-based prescription (1 m(2) = 30 kg)...
April 2016: Cancer Chemotherapy and Pharmacology
Tetsuya Kaneko, Takashi Fujioka, Yosuke Suzuki, Yuhki Sato, Hiroki Itoh
BACKGROUND: High-dose methotrexate (HDMTX) is used in the treatment of certain malignancies, including leptomeningeal metastases, systemic non-Hodgkin lymphoma, acute lymphoblastic leukemia, and osteosarcoma. High circulating levels of methotrexate can cause severe myelosuppression. The present study aimed to examine the differences in plasma MTX concentrations measured by two immunoassay systems currently available in the Japanese market, a TDX/FLX analyzer and a TBA-25FR analyzer. METHODS: A total of 69 plasma samples from 16 patients were assayed by a fluorescence polarization immunoassay technique using a TDx/FLx analyzer (Abbott Diagnostics, Chicago, Illinois, U...
2016: Journal of Pharmaceutical Health Care and Sciences
Rosy Dabas, Rachelle Lee, Maria Theresa Servito, Poonam Dharmani-Khan, Monica Modi, Tiffany van Slyke, Joanne Luider, Caylib Durand, Loree Larratt, Joseph Brandwein, Don Morris, Andrew Daly, Faisal M Khan, Jan Storek
In contrast to cyclosporine or methotrexate, rabbit antithymocyte globulin (ATG) used for graft-versus-host disease (GVHD) prophylaxis with myeloablative conditioning does not increase the risk of relapse after hematopoietic cell transplantation. The reason for this is unknown. We hypothesized that ATG at concentrations achieved with our standard ATG dose of 4.5 mg/kg exerts antileukemic activity. We measured ATG-induced killing of leukemic blasts via complement-dependent cytotoxicity (CDC) and via complement-independent cytotoxicity (CIC) in marrow or blood from 36 patients with newly diagnosed acute leukemia...
May 2016: Biology of Blood and Marrow Transplantation
Priya Tiwari, M K Thomas, Subha Pathania, Deepa Dhawan, Y K Gupta, Sreenivas Vishnubhatla, Sameer Bakhshi
Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours...
2015: Pediatric Hematology and Oncology
Shinichi Kako, Yu Akahoshi, Naonori Harada, Hirofumi Nakano, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Ryoko Yamasaki, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Junji Nishida, Yoshinobu Kanda
The effects of intensive regimens and the roles of drugs used might differ between T- and B-lineage acute lymphoblastic leukemia (ALL). We performed a literature search for clinical studies published from January 1998 to March 2013. Studies were eligible for inclusion in the analyses if they included more than 80 patients with adult ALL who were treated with a uniform regimen and compared T- and B-lineage ALL. Studies that included only adolescent or elderly patients were excluded. We identified 11 clinical studies, which included a total of 381 and 1366 patients with T- and B-lineage ALL, respectively, and performed meta-analyses using the selected studies...
January 2016: Annals of Hematology
M Guren Dolu, A Canbolat Ayhan, M Erguven, C Timur, A Yoruk, S Ozdemir
AIM: Aim of the study was to assess bone metabolism disturbances in children with acute lymphoblastic leukemia following cessation of chemotherapy. For this purpose we measured bone mineral density (BMD) and evaluated bone metabolism markers. METHODS: Seventy-five patients (37 female, 38 males, mean age 10.77±3.80 years) were included. Lumbar spine BMD was measured by dual energy X-ray absorptiometry and serum calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone and 25OH vitamin D levels were analyzed...
October 2015: Minerva Pediatrica
Yuan-dong Li, Yan Li, Ning-sheng Liang, Fan Yang, Zhi-peng Kuang
A simple, rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method has been developed for the determination of methotrexate in human serum. After deproteinization of the serum with 40% silver nitrate solution, methotrexate and internal standard (IS) were separated on a reversed-phase column with a mobile phase consisting of 10mM sodium phosphate buffer (pH6.40)-methanol (78:22%, v/v) and ultraviolet detection at 310nm. The linearity is evaluated by a calibration curve in the concentration range of 0...
October 1, 2015: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Farhad Ravandi, Susan M O'Brien, Jorge E Cortes, Deborah M Thomas, Rebecca Garris, Stefan Faderl, Jan A Burger, Michael E Rytting, Alessandra Ferrajoli, William G Wierda, Srdan Verstovsek, Richard Champlin, Partow Kebriaei, Deborah A McCue, Xuelin Huang, Elias Jabbour, Guillermo Garcia-Manero, Zeev Estrov, Hagop M Kantarjian
BACKGROUND: The long-term efficacy of a combination of chemotherapy and dasatinib in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is not well established. METHODS: Patients received dasatinib with 8 cycles of alternating hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and high-dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine, and prednisone for 2 years, which was followed by dasatinib indefinitely...
December 1, 2015: Cancer
Véronique Minard-Colin, Laurence Brugières, Alfred Reiter, Mitchell S Cairo, Thomas G Gross, Wilhelm Woessmann, Birgit Burkhardt, John T Sandlund, Denise Williams, Marta Pillon, Keizo Horibe, Anne Auperin, Marie-Cécile Le Deley, Martin Zimmerman, Sherrie L Perkins, Martine Raphael, Laurence Lamant, Wolfram Klapper, Lara Mussolin, Hélène A Poirel, Elizabeth Macintyre, Christine Damm-Welk, Angelo Rosolen, Catherine Patte
Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate...
September 20, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Seham M Ragab, Eman A Badr
BACKGROUND/OBJECTIVES: Fetuin-A is a multifunctional protein with its urine level was considered as a marker of acute kidney injury. We investigated the serum and urine fetuin-A in acute lymphoblastic leukemia (ALL) children during and after high-dose methotrexate (HDMTX). METHODS: Twenty-two ALL children and 20 matched healthy controls were included. Liver transaminases, serum creatinine, estimated glomular filtration rate (eGFR), creatinine clearance (CrCl), serum β2 microglobulin (B2M), and serum and urine fetuin-A levels were assayed pre and 4 months after the consolidation...
March 2016: Hematology (Amsterdam, Netherlands)
Ye Meng, Ying Zhang, Mei Liu, Yong Kun Huang, Jun Zhang, Qin Yao, Ya Ling Zhao, Jing Jing Xiong
BACKGROUND AND AIM: The incidence of acute lymphoblastic leukemia (ALL) is highest in childhood malignant tumor in China. The high-dose methotrexate (HDMTX) treatment is very effective in ALL, and it can improve event-free survival rate. However, while executing the anti-tumor effect, it produces highly toxic effects on rapidly dividing cells which are normal. It seems probable that the HDMTX treatment injures intestinal mucosal barrier. The changes of intestinal mucosal barrier can be evaluated through measuring the level of plasma endotoxin and diamine oxidase (DAO)...
2016: Anti-cancer Agents in Medicinal Chemistry
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