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Background/purpose: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear.Methods: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry.Results: MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively.Conclusion: In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1. [ABSTRACT FROM AUTHOR]

Intussusception is a common cause of abdominal pain in children. Although most cases are idiopathic, about 10% of cases have a pathologic lead point. Burkitt''s lymphoma is not a common etiology. Burkitt''s lymphoma might present primarily as intussusception in children but has rarely been associated with appendicitis. We report a case in which a 10-year-old obese boy who initially presented with acute appendicitis due to ileocolic intussusception with appendiceal invagination. He underwent one-trocar laparoscopy and antibiotic treatment. The symptoms recurred 10 days after discharge. Colonoscopy disclosed ileocecal Burkitt''s lymphoma as the pathological lead point. This case emphasizes the importance of the age of the patient and the anatomic location of the intussusception related to possible etiology, and hence the most appropriate surgical procedure. [Copyright &y& Elsevier]

Abstract: Minimal residual disease (MRD) in 56 children with acute lymphoblastic leukemia (ALL) was quantified simultaneously by flow cytometry and by RQ-PCR of WT1 transcripts. Six patients failed remission induction, all had detectable MRD by flow cytometry, and two had undetectable MRD by WT1 assay. Among 41 patients, who achieved remission and had overexpression of WT1 transcripts at diagnosis, the two techniques gave concordant MRD results in 26 and discordant MRD results in 15. Nine patients did not show overexpression of WT1 at diagnosis. Our results indicate that RQ-PCR measurements of WT1 may be of limited value for monitoring MRD in childhood ALL. [Copyright &y& Elsevier]

In the study, the novel fan-out wafer level packaging (FOWLP) technology is presented in which the through silicon via (TSV) array interposer layer is manufactured. Compared to conventional FOWLP technology, the present novel FOWLP technology has several advantages of better signal integrity, higher electrical performance, and easier customization. However, similar to the conventional FOWLP technology, the process-induced warpage resulted from the mismatch of the coefficient of thermal expansion (CTE) among the constituent materials is also an essential issue during the fan-out fabrication process, which is notably for successful process integration. This study proposes a comprehensive assessment of the process-induced warpage of the novel FOWLP during the fan-out fabrication process. A process-dependent simulation methodology is introduced, which integrates nonlinear finite element (FE) analysis incorporated with the element death-birth technique. The study starts from establishing a silicon interposer layer with TSV array, attachment of glass carrier, multiple redistribution layers (RDLs), and dielectric layers. The warpage evolution during the fan-out fabrication process is thoroughly evaluated according to the temperature loading profile. To demonstrate the effectiveness of the proposed theoretical model, the novel FOWLP test vehicle is manufactured for experimental measurement. Finally, the parametric study together with response surface methodology is further applied to provide guidelines for suppressing the warpage. Overall, the simulation modeling represents a feasible approach for predicting the process-induced warpage during the fan-out fabrication process. • A thorough investigation of the process-induced warpage of the novel FOWLP during fabrication process is performed. • The nonlinear finite element analysis with the element death-birth technique is used to assess the process-induced warpage. • The process-induced warpage is affected by the glass carrier CTE and Cu volume fraction in RDL. • Warpage of the novel FOWLP test vehicle is measured by the optical profilometry system using infrared interferometry. • The parametric study with response surface methodology is used to provide guidelines for suppressing the warpage. [ABSTRACT FROM AUTHOR]

With the improvement of the survival rates in children acute lymphoblastic leukemia (ALL), some children ALL survivors show impaired cognitive function. Methotrexate (MTX), an essential component in ALL treatment, has been reported to be related to neurologic sequelae and to increased oxidative stress through its interactions with enzymes in the folate pathway. Asymmetric dimethylarginine (ADMA) is the main endogenous inhibitor of nitric oxide synthase, and increased ADMA may result from increased oxidants. Melatonin is an antioxidant; however, its role in MTX neuropathy is not well studied. We developed a rat model mimicking child ALL treatment to explore peripheral and central homocysteine and ADMA regulation after MTX and found potential treatment choice. Preweaning male Sprague-Dawley rats were used in this study. Experiment 1 evaluated spatial performance in rats with intrathecal (IT) MTX, intraperitoneal (IP) MTX, or combined IT and IP MTX, protocols mimicking ALL treatment in children. Experiment 2 focused on rats with combined IT and IP MTX, evaluating spatial performance and plasma and dorsal hippocampal homocysteine and ADMA levels, their regulation, and the protective effect of melatonin. Combined IT and IP MTX treatment caused in spatial deficits in developing rats, and melatonin restored the spatial performance. Alterations in peripheral and central homocysteine and ADMA concentrations and their regulation were found and could be alleviated by melatonin treatment. Combined IP and IT MTX treatment caused spatial deficits in developing rats. Melatonin could restore spatial performance through alleviating the effects on the imbalance of oxidative stress. [ABSTRACT FROM AUTHOR]