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Pediatric Acute Lymphoblastic Leukemia

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https://www.readbyqxmd.com/read/29455107/helios-expression-in-regulatory-t-cells-promotes-immunosuppression-angiogenesis-and-the-growth-of-leukemia-cells-in-pediatric-acute-lymphoblastic-leukemia
#1
Xue Li, Dong Li, Xiaoyang Huang, Panpan Zhou, Qing Shi, Bing Zhang, Xiuli Ju
Regulatory T cells (Tregs) characterized by the transcription factor forkhead box P3 (FoxP3) are crucial for maintaining immune tolerance and preventing autoimmunity. However, FoxP3 does not function alone and Helios is considered a potential candidate for defining Treg subsets. In this study, we investigated the expression and function of Helios for identifying Tregs in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that patients with pre-B ALL had a higher percentage of Helios+ FoxP3+ CD4+ Tregs...
February 14, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29450465/pediatric-inspired-treatment-regimens-for-adolescents-and-young-adults-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia-a-review
#2
Stuart E Siegel, Wendy Stock, Rebecca H Johnson, Anjali Advani, Lori Muffly, Dan Douer, Damon Reed, Mark Lewis, David R Freyer, Bijal Shah, Selina Luger, Brandon Hayes-Lattin, Jerry J Jaboin, Peter F Coccia, Daniel J DeAngelo, Nita Seibel, Archie Bleyer
Importance: The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL...
February 15, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29449434/msh6-haploinsufficiency-at-relapse-contributes-to-the-development-of-thiopurine-resistance-in-pediatric-b-lymphoblastic-leukemia
#3
Nikki A Evensen, P Pallavi Madhusoodhan, Julia Meyer, Jason Saliba, Ashfiyah Chowdhury, David J Araten, Jacob Nersting, Teena Bhatla, Tiffaney L Vincent, David Teachey, Stephen P Hunger, Jun Yang, Kjeld Schmiegelow, William L Carroll
Survival of children with relapsed acute lymphoblastic leukemia is poor and understanding mechanisms underlying resistance is essential in developing new therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA Mismatch Repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance or leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29442287/recent-developments-in-adolescent-and-young-adult-aya-acute-lymphoblastic-leukemia
#4
REVIEW
Victor M Orellana-Noia, Michael G Douvas
PURPOSE OF REVIEW: Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years...
February 14, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29438132/successful-combination-therapy-of-liposomal-amphotericin-b-and-caspofungin-for-disseminated-fusariosis-in-a-pediatric-patient-with-acute-lymphoblastic-leukemia
#5
Suguru Uemura, Akihiro Tamura, Nobuyuki Yamamoto, Atsuro Saito, Sayaka Nakamura, Takahiro Fujiwara, Teppei Tahara, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Daiichiro Hasegawa, Yasunori Muraosa, Katsuhiko Kamei, Yoshiyuki Kosaka
Disseminated fusariosis is a fatal infection in immunocompromised hosts. However, the optimal antifungal treatment for disseminated fusariosis has not yet been established. We report a case of disseminated fusariosis after chemotherapy for acute lymphoblastic leukemia, presenting with multiple skin, lung, and kidney lesions and cerebrospinal fluid invasion. The combination therapy of liposomal amphotericin B and caspofungin resolved disseminated fusariosis successfully.
February 12, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29438091/a-phase-i-dose-escalation-study-of-clofarabine-in-patients-with-relapsed-or-refractory-low-grade-or-intermediate-grade-b-cell-or-t-cell-lymphoma
#6
Francine Marie Foss, Terri Parker
LESSONS LEARNED: Clofarabine can be active in relapsed and refractory lymphoid malignancies on a weekly dosing schedule.Responses were seen in patients with T-cell lymphomas, including cutaneous T-cell lymphoma, but not in patients with aggressive B-cell lymphomas. BACKGROUND: Clofarabine is a second-generation purine nucleoside analog currently approved for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. In adults, clofarabine has been investigated in several phase I and II trials as a single agent and in combination for relapsed or refractory acute leukemia...
February 7, 2018: Oncologist
https://www.readbyqxmd.com/read/29434778/application-of-gata-3-gene-marker-in-the-detection-of-hematologic-disorders-in-children
#7
Fenghua Wang, Lili Bie
The aim of the present study was to investigate the use of GATA-3 markers in the detection of hematologic disorders in children. In total, 35 pediatric patients diagnosed with blood disease and treated in Henan Red Cross Blood Center from January 2014 to June 2015 were selected for the observation group. Another 32 healthy children were selected for the control group. The differences in the GATA-3 mRNA expression levels between the control and observation groups were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR)...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29431566/levocarnitine-for-asparaginase-induced-hepatic-injury-a-multi-institutional-case-series-and-review-of-the-literature
#8
Rachael R Schulte, Manasi V Madiwale, Allyson Flower, Jessica Hochberg, Michael J Burke, Jennifer L McNeer, Adam DuVall, Archie Bleyer
Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy...
February 12, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29429058/immunosuppressive-monocytes-cd14-hla-dr-low-increase-in-childhood-precursor-b-cell-acute-lymphoblastic-leukemia-after-induction-chemotherapy
#9
D S Lima, R P G Lemes, D M Matos
In tumor microenvironment, immunosuppression is a common event and results from the inhibition of activated immune cells and generation of cells with immunosuppressive capacity, as some subtypes of monocytes. The aim of this study was to evaluate the presence of immunosuppressive CD14 + /HLA-DR low/- monocytes in pediatric patients with the diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) and, moreover, verify whether the chemotherapeutic treatment has any effect on these cells. Peripheral blood (PB) and bone marrow (BM) samples were collected from 15 untreated pediatric patients...
February 10, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29426774/does-ciprofloxacin-prophylaxis-during-chemotherapy-induce-intestinal-microflora-resistance-to-ceftazidime-in-children-with-cancer
#10
Wanutsanun Tunyapanit, Sureerat Chelae, Kamolwish Laoprasopwattana
To determine the susceptibility and minimal inhibitory concentrations (MIC) of ceftazidime, the commonly used empirical antibiotic in patients with febrile neutropenia, in Escherichia coli and Klebsiella pneumoniae isolated from the intestinal microflora of pediatric patients with cancer, who received ciprofloxacin prophylaxis during chemotherapy, children younger than 18 years with acute lymphoblastic leukemia or lymphoma scheduled to undergo chemotherapy were randomized to receive oral ciprofloxacin 20 mg/kg/day or placebo from the beginning of their chemotherapy...
February 6, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29419426/heterozygous-carriers-of-germline-c-657_661del5-founder-mutation-in-nbn-gene-are-at-risk-of-central-nervous-system-relapse-of-b-cell-precursor-acute-lymphoblastic-leukemia
#11
Bartlomiej Tomasik, Agata Pastorczak, Wojciech Fendler, Marcin Bartlomiejczyk, Marcin Braun, Marcin Mycko, Joanna Madzio, Ewa Polakowska, Edyta Ulińska, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Wanda Badowska, Bernarda Kazanowska, Tomasz Szczepański, Jan Styczyński, Nina Irga-Jaworska, Wojciech Młynarski
No abstract text is available yet for this article.
February 1, 2018: Haematologica
https://www.readbyqxmd.com/read/29418064/acute-lymphoblastic-leukemia-and-lymphoblastic-lymphoma-in-adolescents-and-young-adults
#12
REVIEW
Jennifer L McNeer, Archie Bleyer
Compared to younger and older age groups, the incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) has increased more in the adolescent and young adult (AYA) population, the cause of which is unknown. As of the last decade, only half of the AYA patients with these diseases were surviving 10 years. Strong evidence exists that favors "pediatric" treatment regimens for AYAs compared to "adult" treatment regimens in terms of survival rates, hospitalization time, toxicities, late effects, and quality of life both during and after treatment...
February 8, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29416770/hprt1-activity-loss-is-associated-with-resistance-to-thiopurine-in-all
#13
Fan Yang, Houshun Fang, Dan Wang, Yao Chen, Yonggong Zhai, Bin-Bing S Zhou, Hui Li
Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Thiopurine is a widely used drug in the maintaining treatment of ALL. After a period of chemotherapy, 20% of pediatric patients and over 50% of adult patients will relapse. To investigate the mechanisms of drug resistance in vitro, we established the thiopurine resistant cell lines Reh-6MPR (6-MP Resistant cell) and Reh-6TGR (6-TG Resistant cell) by stepwise selection of the ALL cell line Reh...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415942/-initial-presentation-of-lymphoblastic-crisis-in-a-pediatric-chronic-myelogenous-leukemia-patient
#14
Kosuke Akiyama, Shohei Yamamoto, Yumiko Sugishita, Ryota Kaneko, Naoko Okamoto, Masaya Koganesawa, Sachio Fujita, Ryosuke Matsuno, Daisuke Toyama, Keiichi Isoyama
A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29415326/proportion-of-pediatric-acute-lymphoblastic-leukemia-patients-who-continue-hospital-visits
#15
Naoko Maeda, Akiko Saito, Akiko Kada, Toshihiko Imamura, Akira Hayakawa, Keizo Horibe, Atsushi Sato
BACKGROUND: Long-term follow-up in adulthood after childhood cancer therapy is particularly important because of the risk of late effects, and information on the rate of continuing hospital visits by childhood cancer survivors (CCSs) is also important for the planning of studies on the risk of late effects. METHODS: The rate of continuing hospital visits ("long-term follow-up") in 1,252 cases registered in the multicenter Japan Association of Childhood Leukemia Study on Acute Lymphoblastic Leukemia (JACLS ALL-02) was investigated using data from its electronic data capture (EDC) system, including case number, date of diagnosis, date of therapy completion, date of birth, sex, survival or death, date of death, date of last outcome confirmation, and facility code...
February 7, 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/29408328/ribociclib-a-cdk4-cdk6-kinase-inhibitor-enhances-glucocorticoid-sensitivity-in-b-acute-lymphoblastic-leukemia-b-all
#16
Roberta Bortolozzi, Elena Mattiuzzo, Luca Trentin, Benedetta Accordi, Giuseppe Basso, Giampietro Viola
Dysregulation of the cyclin D1-CDK4/CDK6 complex is frequently observed in almost all human cancer and contributes to aberrant cell proliferation and consequent tumorigenesis. Although many reports described the importance of CDK4/CDK6 in different set of human tumors, only few studies have been performed on leukemia. By gene expression analysis performed in a cohort of childhood patients affected by B-acute lymphoblastic leukemia (B-ALL) we found that both CDK4 and CDK6 are highly expressed. Moreover, Reverse Phase Protein Array (RPPA) analysis showed that cyclin D1 levels are higher in patients undergoing relapse...
February 3, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29407587/high-frequency-of-intermediate-and-poor-risk-copy-number-abnormalities-in-pediatric-cohort-of-b-all-correlate-with-high-mrd-post-induction
#17
Minu Singh, Prateek Bhatia, Amita Trehan, Neelam Varma, Manupdesh Singh Sachdeva, Deepak Bansal, Richa Jain, Shano Naseem
Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29407583/pegaspargase-related-high-grade-hepatotoxicity-in-a-pediatric-inspired-adult-acute-lymphoblastic-leukemia-regimen-does-not-predict-recurrent-hepatotoxicity-with-subsequent-doses
#18
Patrick W Burke, Ibrahim Aldoss, Matthew A Lunning, Sean M Devlin, Martin S Tallman, Vinod Pullarkat, Ann M Mohrbacher, Dan Douer
Pediatric acute lymphoblastic leukemia (ALL) regimens, including higher cumulative asparaginase doses, have been investigated in adult ALL to improve outcomes. Preliminary results are promising, but hepatotoxicity rates with long-acting pegaspargase are greater in adults than children. However, adult pegaspargase-related hepatotoxicity is not as clearly defined despite being the commonest adult toxicity. We studied the frequency and characteristics of high-grade pegaspargase-related hepatotoxicity in newly diagnosed adults on a pediatric-inspired regimen that included six planned pegaspargase doses, 2000 IU/m2/dose intravenously, with doses given at least four weeks apart and not discontinued or dose-reduced for previous hepatotoxicity...
January 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29401102/acquired-hypofibrinogenemia-before-asparaginase-exposure-during-induction-therapy-for-pediatric-acute-lymphoblastic-leukemia-a-report-of-2-cases-and-review-of-the-literature
#19
Sunil S Raikar, James Felker, Kavita N Patel, Glen Lew, Robert F Sidonio
Coagulopathy in pediatric leukemia patients is typically associated with acute promyelocytic leukemia or after asparaginase use in acute lymphoblastic leukemia. Rarely seen in acute lymphoblastic leukemia, we report 2 patients who presented with normal coagulation markers, but subsequently developed severe hypofibrinogenemia and bleeding in induction before administration of asparaginase. In both cases, cryoprecipitate was administered as initial treatment for bleeding associated with the hypofibrinogenemia...
February 2, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29398803/therapy-related-aml-mds-following-treatment-for-childhood-cancer-experience-from-a-tertiary-care-centre-in-north-india
#20
Chintan Vyas, Sandeep Jain, Gauri Kapoor
Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P = 0.26] with 6390 patient years of follow up...
January 2018: Indian Journal of Hematology & Blood Transfusion
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