Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: A retrospective intergroup study

Genetic abnormalities and early treatment response are the main prognostic factors in acute myeloid leukemia (AML). Acute megakaryoblastic leukemia (AMKL) is a rare subtype of AML. Deep sequencing has identified CBFA2T3/GLIS2 and NUP98/KDM5A as recurrent aberrations, occurring in similar frequencies as RBM15/MKL1 and KMT2A-rearrangements. We studied whether these cytogenetic aberrations can be used for risk group stratification. To assess frequencies and outcome parameters of recurrent cytogenetic aberrations in AMKL, samples and clinical data of patients treated by the Associazione Italiana Ematologia Oncologia Pediatrica, Berlin-Frankfurt-Munster Study Group, Children's Oncology Group, Dutch Childhood Oncology Group, and the Saint Louis Hôpital were collected, enabling us to screen 153 newly diagnosed pediatric AMKL cases for the aforementioned aberrations and to study their clinical characteristics and outcome. CBFA2T3/GLIS2 was identified in 16% of the cases; RBM15/MKL1, in 12%; NUP98/KDM5A and KMT2A rearrangements, in 9% each; and monosomy 7, in 6%. These aberrations were mutually exclusive. RBM15/MKL1-rearranged patients were significantly younger. No significant differences in sex and white blood cell count were found. NUP98/KDM5A, CBFA2T3/GLIS2, KMT2A-rearranged lesions and monosomy 7 (NCK-7) independently predicted a poor outcome, compared with RBM15/MKL1-rearranged patients and those with AMKL not carrying these molecular lesions. NCK-7-patients (n = 61) showed a 4-year probability of overall survival of 35 ± 6% vs 70 ± 5% in the RBM15/MKL1-other groups (n = 92, P < .0001) and 4-year probability of event-free survival of 33 ± 6% vs 62 ± 5% (P = .0013), the 4-year cumulative incidence of relapse being 42 ± 7% and 19 ± 4% (P = .003), respectively. We conclude that these genetic aberrations may be used for risk group stratification of pediatric AMKL and for treatment tailoring

Screening Tools Assessing Risk of Suicide and Self-Harm in Adult Offenders: A Systematic Review

This systematic review assessed the validity of screening instruments to identify the risk of suicide and self-harm behaviour in offenders. A search of 11 electronic databases and grey literature resulted in the inclusion of five studies. The five studies revealed four screening instruments, including the Suicide Checklist, the Suicide Probability Scale, Suicide Concerns for Offenders in Prison Environment (SCOPE), and the Suicide Potential Scale. Two instruments, SCOPE and Suicide Potential Scale, shared promising levels of sensitivity and specificity. The reporting of information was generally varied across items on the Standards for the Reporting of Diagnostic accuracy (STARD). Research is needed to assess the predictive validity of tools for offender populations in the identification of those at risk, particularly those in probation and community settings

Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study

Monosomy 7 (-7) and deletion 7q [del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and -7 or del(7q) with or without other cytogenetic aberrations [+/- other]. Karyotypes included -7 (n = 90), -7 other (n = 82), del(7q) (n = 21), and del(7q) other(n = 65). Complete remission (CR) was achieved in fewer patients with -7 +/- other compared with del(7q) +/- other (61% versus 89%, P &lt;.001). Overall, the 5-year survival rate was 39% (SE, 3%). Survival was superior in del(7q) +/- other compared with -7 other (51 % versus 30%, P &lt;.01). Cytogenetic aberrations considered favorable in AML [t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(9;11)(p22;q23)] (n = 24) were strongly associated with del(7q) and a higher 5-year survival rate compared with del(7q) without favorable cytogenetics (75% versus 46%, P =.03). Patients with -7 and inv(3),-5/del(5q), or +21 had a 5-year survival rate of 5%. Stem cell transplantation analyzed as a time-dependent variable had no impact on overall survival. However, patients not achieving CR had a 31% survival rate after stem cell transplantation. Childhood AML with chromosome 7 aberrations represents a heterogeneous group of disorders with additional cytogenetic aberrations having a major prognostic impact which should be reflected in future risk-group stratificatio

Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: A collaborative study by the International-Berlin- Frankfurt-Münster AML-study group

In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P =.14). Gene expression profiles of t(8;16) (p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases

Measurement of the Z0 branching fraction to b quark pairs using the boosted sphericity product

From a sample of about 120 000 hadronic Z0 decays, using a technique based on a separation of the different event categories in the boosted sphericity product, the fraction of bb̄ decays has been measured to be 0.219 ± 0.014 (stat) ⋯ 0.019 (syst). Using the DELPHI determination of the hadronic Z0 width, this corresponds to a partial width Γbb- = 378 ± 42 MeV (in good agreement with the standard model prediction of ≃ 380 MeV). Combining this measurement with the determinations based on events with high pt leptons gives an estimate for the branching ratio of b into leptons at LEP of (11.2 ± 1.2)%, consistent with previous determinations.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Energy-energy correlations in hadronic final states from Z0 decays

We have studied the energy-energy angular correlations in hadronic final states from Z0 decay using the DELPHI detector at LEP. From a comparison with Monte Carlo calculations based on the exact second order QCD matrix element and string fragmentation we find that Λ(5)/MS = 104-20 +25 (stat.)-20 +25(syst.)-00 +30(theor.) MeV, which corresponds to αs(91 GeV) = 0.106± 0.003 (stat.)±0.003(syst.)-0.000 +0.003(theor.). The theoretical error stems from different choices for the renormalization scale of αs. In the Monte Carlo simulation the scale of αs as well as the fragmentation parameters have been optimized to described reasonably well all aspects of multihadron production.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe