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high dose methotrexate in acute leukemia

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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
#1
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
#2
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 includes 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients...
February 2, 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
#3
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...
January 31, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29328996/acute-and-sub-acute-neurological-toxicity-in-children-treated-for-acute-lymphoblastic-leukemia
#4
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
#5
Julio C Barredo, Caroline Hastings, Xiamin Lu, F 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...
December 29, 2017: 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
#6
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...
December 23, 2017: 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
#7
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...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29146215/-acute-methotrexate-related-neurotoxicity-and-pseudo-stroke-syndrome
#8
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"...
November 13, 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
#9
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)...
November 16, 2017: 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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/29046900/us-intergroup-study-of-chemotherapy-plus-dasatinib-and-allogeneic-stem-cell-transplant-in-philadelphia-chromosome-positive-all
#13
Farhad Ravandi, Megan Othus, Susan M O'Brien, Stephen J Forman, Chul S Ha, Jeffrey Y C Wong, Martin S Tallman, Elisabeth Paietta, Janis Racevskis, Geoffrey L Uy, Mary Horowitz, Naoko Takebe, Richard Little, Uma Borate, Partow Kebriaei, Laura Kingsbury, Hagop M Kantarjian, Jerald P Radich, Harry P Erba, Frederick R Appelbaum
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100...
December 27, 2016: Blood Advances
https://www.readbyqxmd.com/read/29031010/evaluation-of-aprepitant-for-acute-chemotherapy-induced-nausea-and-vomiting-in-children-and-adolescents-with-acute-lymphoblastic-leukemia-receiving-high-dose-methotrexate
#14
Femi Felix-Ukwu, Kate Reichert, M Brooke Bernhardt, Eric S Schafer, Amanda Berger
BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) negatively impacts patients' quality of life. The emetogenicity of high-dose methotrexate in children and adolescents with cancer is incompletely characterized. At our institution, a number of patients with acute lymphoblastic leukemia (ALL) have received aprepitant with courses of high-dose methotrexate after poor CINV control with prior courses. PROCEDURE: We conducted a retrospective cohort analysis on patients with ALL who received methotrexate 5 g/m(2) /dose with and without concomitant aprepitant at Texas...
October 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28914260/high-dose-methotrexate-therapy-significantly-improved-survival-of-adult-acute-lymphoblastic-leukemia-a-phase-iii-study-by-jalsg
#15
T Sakura, F Hayakawa, I Sugiura, T Murayama, K Imai, N Usui, S Fujisawa, T Yamauchi, T Yujiri, K Kakihana, Y Ito, H Kanamori, Y Ueda, Y Miyata, M Kurokawa, N Asou, K Ohnishi, S Ohtake, Y Kobayashi, K Matsuo, H Kiyoi, Y Miyazaki, T Naoe
High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Philadelphia chromosome (Ph)-negative ALL patients aged between 25 and 64 years of age were enrolled...
September 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28774365/-neurocognitive-function-of-children-with-acute-lymphoblastic-leukemia-and-long-term-disease-free-survival-and-related-influencing-factors
#16
Xiao-Yan Fu, Xiao-Tian Xie, Yan Zhao
OBJECTIVE: To investigate the neurocognitive function of children with acute lymphoblastic leukemia (ALL) and long-term disease-free survival and related influencing factors. METHODS: A total of 40 ALL children with long-term disease-free survival were enrolled as study group, and 40 healthy children were enrolled as control group. The Chinese Wechsler Intelligence Scale for Children (C-WISC), continuous performance test (CPT), and Stroop test software were used for the evaluation of all children...
August 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28767288/arsenic-trioxide-consolidation-allows-anthracycline-dose-reduction-for-pediatric-patients-with-acute-promyelocytic-leukemia-report-from-the-children-s-oncology-group-phase-iii-historically-controlled-trial-aaml0631
#17
MULTICENTER STUDY
Matthew A Kutny, Todd A Alonzo, Robert B Gerbing, Yi-Cheng Wang, Susana C Raimondi, Betsy A Hirsch, Cecilia H Fu, Soheil Meshinchi, Alan S Gamis, James H Feusner, John J Gregory
Purpose The Children's Oncology Group AAML0631 trial for newly diagnosed pediatric acute promyelocytic leukemia (APL) was a phase III historically controlled trial to determine the survival of patients receiving arsenic trioxide (ATO) consolidation and reduced doses of anthracyclines. Patients and Methods Patients age 2 to 21 years with de novo APL confirmed by PML-RARα polymerase chain reaction were stratified as standard risk (SR) or high risk (HR) on the basis of diagnostic WBC count. All patients received all-trans retinoic acid (ATRA) during induction, each consolidation course, and maintenance...
September 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28697831/-adverse-effects-of-high-dose-methotrexate-therapy
#18
Qing Sun, Yao Xie, Wei-Hong Zhao, Ying Hua, Peng-Hui Wu, Shuo Li, Xin-Tian Lu
OBJECTIVE: To investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment. METHODS: A retrospective analysis was performed for the clinical data of 120 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent 601 times of HDMTX therapy. The adverse effects of various systems were analyzed according to the WHO criteria for the classification of adverse effects of anticancer drugs...
July 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28693140/acute-myeloid-leukemia-with-t-3-21-q26-2-q22-developing-following-low-dose-methotrexate-therapy-for-rheumatoid-arthritis-and-expressing-two-aml1-mds1-evi1-fusion-proteins-a-case-report
#19
Keisuke Tanaka, Gaku Oshikawa, Hiroki Akiyama, Shinya Ishida, Toshikage Nagao, Masahide Yamamoto, Osamu Miura
The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)-ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28671857/neurocognitive-functioning-of-children-treated-for-high-risk-b-acute-lymphoblastic-leukemia-randomly-assigned-to-different-methotrexate-and-corticosteroid-treatment-strategies-a-report-from-the-children-s-oncology-group
#20
RANDOMIZED CONTROLLED TRIAL
Kristina K Hardy, Leanne Embry, John A Kairalla, Shanjun Helian, Meenakshi Devidas, Daniel Armstrong, Stephen Hunger, William L Carroll, Eric Larsen, Elizabeth A Raetz, Mignon L Loh, Wenjian Yang, Mary V Relling, Robert B Noll, Naomi Winick
Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue...
August 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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