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Acute Lymphoblastic leukemia in adults

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https://www.readbyqxmd.com/read/28436558/adverse-effects-of-pegaspargase-in-pediatric-patients-receiving-doses-greater-than-3-750%C3%A2-iu
#1
Rachel Lebovic, Natalie Pearce, Laura Lacey, James Xenakis, Cassidy B Faircloth, Patrick Thompson
BACKGROUND: Increased toxicities have been identified with higher doses of pegaspargase (PEG-ASP) in adults. This has led to routine use of a dose cap of 3,750 IU for adult acute lymphoblastic leukemia (ALL) patients in most institutions. In pediatric ALL patients, PEG-ASP is not capped. There is concern at our institution that larger doses may result in increased rates of adverse effects and that increased monitoring may be warranted in pediatric patients receiving doses greater than 3,750 IU...
April 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28428987/microarray-profiling-and-co-expression-network-analysis-of-the-lncrnas-and-mrnas-associated-with-acute-leukemia-in-adults
#2
Hui Cheng, Chong Mei Huang, Yang Wang, Xiao Xia Hu, Xiao Qian Xu, Xian Min Song, Gu Sheng Tang, Li Chen, Jian Min Yang
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis...
April 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28419558/age-but-not-philadelphia-positivity-impairs-outcome-in-older-elderly-patients-with-acute-lymphoblastic-leukemia-in-sweden
#3
Piotr Kozlowski, Emma Lennmyr, Lucia Ahlberg, Per Bernell, Erik Hulegårdh, Holger Karbach, Karin Karlsson, Beata Tomaszewska-Toporska, Maria Åström, Heléne Hallböök
OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. METHODS: Using Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85 years, diagnosed with ALL 2005-2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype...
April 18, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28419486/population-pharmacokinetic-analysis-of-bortezomib-in-pediatric-leukemia-patients-model-based-support-for-body-surface-area-based-dosing-over-the-2-to-16-year-age-range
#4
Michael J Hanley, Diane R Mould, Timothy J Taylor, Neeraj Gupta, Kaveri Suryanarayan, Rachel Neuwirth, Dixie-Lee Esseltine, Terzah M Horton, Richard Aplenc, Todd A Alonzo, Xiaomin Lu, Ashley Milton, Karthik Venkatakrishnan
This population analysis described the pharmacokinetics of bortezomib after twice-weekly, repeat-dose, intravenous administration in pediatric patients participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981) trial in de novo acute myelogenous leukemia. The sources of variability in the pharmacokinetic parameters were characterized and quantified to support dosing recommendations. Patients received intravenous bortezomib 1...
April 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28415593/cysteine-and-glycine-rich-protein-2-csrp2-transcript-levels-correlate-with-leukemia-relapse-and-leukemia-free-survival-in-adults-with-b-cell-acute-lymphoblastic-leukemia-and-normal-cytogenetics
#5
Shu-Juan Wang, Ping-Zhang Wang, Robert Peter Gale, Ya-Zhen Qin, Yan-Rong Liu, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Hui Zhang, Bin Jiang, Lan-Ping Xu, Xiao-Jun Huang, Kai-Yan Liu, Guo-Rui Ruan
Relapse is the major cause of treatment-failure in adults with B-cell acute lymphoblastic leukemia (ALL) achieving complete remission after induction chemotherapy. Greater precision identifying persons likely to relapse is important. We did bio-informatics analyses of transcriptomic data to identify mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate genes for validation 7 of which proved significantly-associated with B-cell ALL. We next focused on function and clinical correlations of the cysteine and glycine-rich protein 2 (CSRP2)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413717/advances-of-cd19-directed-chimeric-antigen-receptor-modified-t-cells-in-refractory-relapsed-acute-lymphoblastic-leukemia
#6
REVIEW
Guoqing Wei, Lijuan Ding, Jiasheng Wang, Yongxian Hu, He Huang
Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28412288/adult-t-type-lymphoblastic-lymphoma-treatment-advances-and-prognostic-indicators
#7
REVIEW
Stéphane Lepretre, Carlos Graux, Aurore Touzart, Elizabeth Macintyre, Nicolas Boissel
T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor T cells that occurs mostly in adolescents and young adults. In this review, we describe the treatment of adult T-LBL with a focus on recent advances using pediatric-inspired acute lymphoblastic leukemia regimens, which have greatly improved outcome. We also discuss the development of prognostic indicators for T-LBL, especially oncogenetic factors, that can identify patients at higher risk of relapse and should help further extend T-LBL patient survival...
April 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28410228/identification-of-a-novel-functional-jak1-s646p-mutation-in-acute-lymphoblastic-leukemia
#8
Qian Li, Botao Li, Liangding Hu, Hongmei Ning, Min Jiang, Danhong Wang, Tingting Liu, Bin Zhang, Hu Chen
The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching 90%, while the prognosis of adults remains poor due to the limited therapeutic approaches. In order to identify new targets for ALL, we performed whole-exome sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two cases exhibited A639G and P960S mutations separately. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#9
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#10
REVIEW
Hanna Karvonen, Wilhelmiina Niininen, Astrid Murumägi, Daniela Ungureanu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28406385/retrospective-chart-review-of-hospitalizations-and-costs-associated-with-the-treatment-of-adults-with-philadelphia-negative-b-cell-relapsed-or-refractory-acute-lymphoblastic-leukemia-in-belgium
#11
Johan Maertens, Carlos Graux, Dimitri Breems, Violaine Havelange, Sebastian Wittnebel, Daniëlle Strens, Caroline Hoefkens
OBJECTIVES: To quantify hospitalizations and costs among adults with Philadelphia-negative relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) who received current salvage chemotherapies in Belgium. METHODS: A retrospective chart review identified patients aged ≥18 years and hospitalized between 2005 and 2015 for Ph-negative R/R B-cell ALL. Data were collected from the index date (first diagnosis of R/R ALL) until death or loss to follow-up...
April 13, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28405496/il-12-il-15-and-il-18-pre-activated-nk-cells-target-resistant-t-cell-acute-lymphoblastic-leukemia-and-delay-leukemia-development-in-vivo
#12
Margherita Boieri, Aina Ulvmoen, Amanda Sudworth, Clare Lendrem, Matthew Collin, Anne M Dickinson, Lise Kveberg, Marit Inngjerdingen
NK cells have shown promise in therapy of hematological cancers, in particular against acute myeloid leukemia. In contrast, the more NK cell-resistant acute lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies, and we hypothesized that pre-activation of NK cells could overcome this resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL) perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401483/molecular-profiling-of-gene-copy-number-abnormalities-in-key-regulatory-genes-in-high-risk-b-lineage-acute-lymphoblastic-leukemia-frequency-and-their-association-with-clinicopathological-findings-in-indian-patients
#13
Prerana Bhandari, Firoz Ahmad, Bibhu Ranjan Das
Genes related to key cellular pathways are frequently altered in B cell ALL and are associated with poor survival especially in high-risk (HR) subgroups. We examined gene copy number abnormalities (CNA) in 101 Indian HR B cell ALL patients and their correlation with clinicopathological features by multiplex ligation-dependent probe amplification. Overall, CNA were detected in 59 (59%) cases, with 26, 10 and 23% of cases harboring 1, 2 or +3 CNA. CNA were more prevalent in BCR-ABL1 (60%), pediatric (64%) and high WCC (WBC count) (63%) patients...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28401103/characterization-of-clonal-immunoglobulin-heavy-igh-v-d-j-gene-rearrangements-and-the-complementarity-determining-region-in-south-indian-patients-with-precursor-b-cell-acute-lymphoblastic-leukemia
#14
Natarajan Sudhakar, Thangarajan Rajkumar, Kamalalayam Raghavan Rajalekshmy, Nirmala Karunakaran Nancy
BACKGROUND: This study characterized clonal IG heavy V-D-J (IGH) gene rearrangements in South Indian patients with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) and identified age-related predominance in VDJ rearrangements. METHODS: IGH rearrangements were studied in 50 precursor B-ALL cases (common ALL=37, pre-B ALL=10, pro-B ALL=3) by polymerase chain reaction (PCR) heteroduplex analysis. Twenty randomly selected clonal IGH rearrangement sequences were analyzed using the IMGT/V-QUEST tool...
March 2017: Blood Research
https://www.readbyqxmd.com/read/28401025/adult-acute-precursor-b-cell-lymphoblastic-leukemia-presenting-as-hypercalcemia-and-osteolytic-bone-lesions
#15
Nikki Charlotta Paul Granacher, Zwi N Berneman, Wilfried Schroyens, Ann L R Van de Velde, Anke Verlinden, Alain P A Gadisseur
BACKGROUND: Osteolytic bone lesions and hypercalcemia without peripheral blasts B-cell acute lymphoblastic leukemia (B-ALL) is reported in children but rarely seen in adults. CASE PRESENTATION: We describe the case of a 34-year old man presenting with hypercalcemia and symptomatic osteolytic bone lesions of vertebrae and ribs who was initially suspected as having a solid malignancy. Diagnostic work-up including peripheral blood examination, radiographic and nuclear studies could, however, not detect a primary tumor...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28396160/allogeneic-hematopoietic-cell-transplantation-hct-for-adult-t-cell-acute-lymphoblastic-leukemia-t-all
#16
Betty Ky Hamilton, Lisa Rybicki, Donna Abounader, Kehinde Adekola, Anjali Advani, Ibrahim Aldoss, Veronika Bachanova, Asad Bashey, Stacey Brown, Marcos DeLima, Steven Devine, Christopher R Flowers, Siddharth Ganguly, Madan Jagasia, Vanessa E Kennedy, Dennis Dong Hwan Kim, Joseph McGuirk, Vinod Pullarkat, Rizwan Romee, Karamjeet Sandhu, Melody Smith, Masumi Ueda, Auro Viswabandya, Khoan Vu, Sarah Wall, Simon B Zeichner, Miguel-Angel Perales, Navneet S Majhail
Allogeneic hematopoietic cell transplantation (HCT) is recommended for T-cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and in high risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multi-center retrospective cohort study using data from 208 adult patients transplanted from 2000-2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. Median age at HCT was 37 years and the majority of patients were transplanted in CR, using total body irradiation (TBI) based myeloablative conditioning regimens...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28395813/prognostic-effect-of-complex-karyotype-monosomal-karyotype-and-chromosome-17%C3%A2-abnormalities-in-b-cell-acute-lymphoblastic-leukemia
#17
Priya Khoral, Eshetu G Atenafu, Kenneth J Craddock, Aaron Schimmer, Hong Chang
BACKGROUND: The effect of monosomal karyotype (MK), complex karyotype (CK), and chromosome 17 abnormalities (abnl 17) on prognosis in B-cell acute lymphoid leukemia (B-ALL) has not yet been established. PATIENTS AND METHODS: We conducted a retrospective analysis of prognostic factors on 237 adult patients with B-ALL treated at our institution. RESULTS: Older age (older than 60 years), higher white blood cell count (> 30), and abnl 17 were associated with shorter overall survival in univariate analysis, but multivariable analysis only identified older age as an independent poor prognostic actor...
April 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28395443/-clinical-analysis-of-adult-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-with-p16-gene-deletion
#18
B L He, N Xu, Y L Li, C Y Pan, R Cao, L B Liao, C X Yin, Y Q Lan, Z Y Lu, J X Huang, H S Zhou, Q F Liu, X L Liu
Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph(+) ALL patients with p16 deletion. Results: Of 80 adult Ph(+) ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10(9)/L) and CD20 expression...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28385156/childhood-pre-b-cell-acute-lymphoblastic-leukemia-with-translocation-t-1-19-q21-1-p13-3-and-two-additional-chromosomal-aberrations-involving-chromosomes-1-6-and-13-a-case-report
#19
Abdulsamad Wafa, Manar As'sad, Thomas Liehr, Abdulmunim Aljapawe, Walid Al Achkar
BACKGROUND: The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20...
April 7, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28384176/sociodemographic-disparities-in-chemotherapy-and-hematopoietic-cell-transplantation-utilization-among-adult-acute-lymphoblastic-and-acute-myeloid-leukemia-patients
#20
Brice Jabo, John W Morgan, Maria Elena Martinez, Mark Ghamsary, Matthew J Wieduwilt
INTRODUCTION: Identifying sociodemographic disparities in chemotherapy and hematopoietic cell transplantation (HCT) utilization for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) may improve survival for underserved populations. In this study, we incorporate neighborhood socioeconomic status (nSES), marital status, and distance from transplant center with previously studied factors to provide a comprehensive analysis of sociodemographic factors influencing treatments for ALL and AML...
2017: PloS One
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