Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE)

Many cutpoints have been proposed to categorize continuous variables in childhood acute lymphoblastic leukaemia (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age), and have been used to define therapeutic subgroups. This variation in the choice of cutpoints leads to a bias called the ‘Will Rogers phenomenon’. The aim of this study was to analyse variations in the relative risk of relapse or death as a function of continuous prognostic variables in childhood ALL and to discuss the choice of cutpoints. We studied a population of 1545 children with ALL enrolled in three consecutive protocols named FRALLE 83, FRALLE 87 and FRALLE 89. We estimated the risk of relapse or death associated with different values of each continuous prognostic variable by dividing the sample into quintiles of the distribution of the variables. As regards age, a category of children under 1 year of age was distinguished and the rest of the population was divided into quintiles. The floated variance method was used to calculate the confidence interval of each relative risk, including the reference category. The relation between the quantitative prognostic factors and the risk was monotonic for each variable, except for age. For the white blood cell count (WBC), the relation is log linear. The risk associated with WBC values in the upper quintile was 1.9 times higher than that in the lower quintile. The peripheral blast cell count correlated strongly with WBC (correlation coefficient: 0.99). The risk increased with the haemoglobin level, and the risk in the upper quintile was 1.3 times higher than that in the lower quintile. The risk decreased as the platelet count increased: the risk in the lower quintile was 1.2 times higher than that in the upper quintile. The risk increased gradually with increasing age above one year. The small subgroup of patients (2.5% of the population) under 1 year of age at diagnosis had a risk 2.6 times higher than the reference category of patients between 3 and 4.3 years of age. When the risk associated with a quantitative prognostic factor varies monotonously, the selection of a cutpoint is arbitrary and represents a loss of information. Despite this loss of information, such arbitrary categorization may be necessary to define therapeutic stratification. In that case, consensus cutpoints must be defined if one wants to avoid the Will Rogers phenomenon. The cutpoints proposed by the Rome workshop and the NCI are arbitrary, but may represent an acceptable convention. © 2000 Cancer Research Campaign http://www.bjcancer.co

Plasma Electronics

Contains reports on nine research projects.U. S. Air Force under Air Force Contract AF 19(604)-7400National Science Foundation under Grant G-9330U.S.Navy(Office of Naval Research)under Contract Nonr-1841(78)U. S. ArmyLincoln Laboratory, Purchase Order DDL B-00337U. S. Nav

Plasma Electronics

Contains research objectives and reports on twelve research projects.National Science Foundation under Grant G-9330U. S. Navy (Office of Naval Research) under Contract Nonr-1841(78)U. S. NavyLincoln Laboratory, Purchase Order DDL B-00306U. S. ArmyU. S. Air Force under Air Force Contract AF19(604)-740

A patient with glycogen storage disease type Ib presenting with acute myeloid leukemia (AML) bearing monosomy 7 and translocation t(3;8)(q26;q24) after 14 years of treatment with granulocyte colony-stimulating factor (G-CSF): A case report

<p>Abstract</p> <p>Introduction</p> <p>Glycogen storage disease type Ib is an autosomal recessive transmitted disorder of glycogen metabolism caused by mutations in the glucose-6-phosphate translocase gene on chromosome 11q23 and leads to disturbed glycogenolysis as well as gluconeogenesis. Besides hepatomegaly, growth retardation, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia, patients suffer from neutropenia associated with functional defects predisposing for severe infections. In order to attenuate these complications, long-term treatment with granulocyte colony-stimulating factor is common but this is associated with an increased risk for acute myeloid leukemia or myelodysplastic syndromes in patients with inherited bone marrow failures such as severe congenital neutropenia. Onset of these myeloid malignancies is linked to cytogenetic aberrations involving chromosome 7. In addition, granulocyte colony-stimulating factor is known to stimulate proliferation of monosomy 7 cells <it>in vitro</it>. To our knowledge, we report for the first time a case report of a patient with glycogen storage disease type Ib, who developed acute myeloid leukemia with a classical monosomy 7 and acute myeloid leukemia-associated translocation t(3;8)(q26;q24) after 14 years of continuous treatment with granulocyte colony-stimulating factor.</p> <p>Case presentation</p> <p>A 28-year-old Turkish man with glycogen storage disease type Ib was admitted to our department because of dyspnea and increasing fatigue. He also presented with gum bleeding, bone pain in his legs, night sweats, recurrent episodes of fever with temperatures up to 39°C and hepatosplenomegaly.</p> <p>A blood count taken on the day of admission showed pancytopenia and a differential count displayed 30% blasts. A bone marrow biopsy was taken which showed a hypercellular marrow with dysplastic features of all three cell lines, while blast count was 20%. Classical cytogenetic analyses as well as fluorescence in situ hybridization showed a monosomy 7 with a translocation t(3;8)(q26;q24). Based on these findings, the diagnosis of acute myeloid leukemia was made.</p> <p>Conclusion</p> <p>Our observations suggest that bone marrow examinations including cytogenetic analysis should be carried out on a regular basis in patients with glycogen storage disease type Ib who are on long-term treatment with granulocyte colony-stimulating factor for severe neutropenia, since this treatment might also contribute to an increased risk for acute myeloid leukemia or myelodysplastic syndromes.</p

Plasma Electronics

Contains research objectives and reports on seven research projects.U. S. ArmyLincoln Laboratory, Purchase Order DDL B-00368U. S. Air Force under Air Force Contract AF19(604)-7400U. S. NavyNational Science Foundation (Grant G-24073)U.S. Navy (Office of Naval Research) under Contract Nonr-1841(78

Plasma Dynamics

Contains reports on three research projects.National Science Foundation under Grant G-9330Air Force Cambridge Research Center under Contract AF-19(604)-5992United States Air Force (WADD Contract AF33(616)-3984)Contract AF19(604)-4551 with Air Force Cambridge Research CenterAeronautical Accessories Laboratory, Wright Air Development Division, Wright-Patterson Air Force Base, Ohio (Air Force Contract AF33(616)-3984, Project 8149, Task No. 61098)Atomic Energy Commission under Contract AT(30-1)-184

Tomosynthesis in pulmonary cystic fibrosis with comparison to radiography and computed tomography: a pictorial review

The purpose of this pictorial review is to illustrate chest imaging findings of cystic fibrosis (CF) using tomosynthesis (digital tomography), in comparison to radiography and computed tomography (CT). CF is a chronic systemic disease where imaging has long been used for monitoring chest status. CT exposes the patient to a substantially higher radiation dose than radiography, rendering it unsuitable for the often needed repeated examinations of these patients. Tomosynthesis has recently appeared as an interesting low dose alternative to CT, with an effective dose of approximately 0.08 mSv for children and 0.12 mSv for adults. Tomosynthesis is performed on the same X-ray system as radiography, adding only about 1 min to the normal examination time. Typical pulmonary changes in CF such as mucus plugging, bronchial wall thickening, and bronchiectases are shown in significantly better detail with tomosynthesis than with traditional radiography. In addition, the cost for a tomosynthesis examination is low compared to CT. To reduce the radiation burden of patients with CF it is important to consider low dose alternatives to CT, especially in the paediatric population. Tomosynthesis has a lower radiation dose than CT and gives a superior visualisation of pulmonary CF changes compared to radiography. It is important to further determine the role of tomosynthesis for monitoring disease progression in CF

In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis

Remyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral inflammatory demyelinating lesions, we investigated whether MRI is sensitive to, and can characterize, remyelination. In six animals followed with multisequence 7 T MRI, 31 focal lesions, predicted to be demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in four of six marmosets and 45% of lesions. Radiological-pathological comparison showed that MRI had high statistical sensitivity (100%) and specificity (90%) for detecting remyelination. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents

Plasma Dynamics

Contains reports on three research projects.Wright Air Development Division (Contract AF33(616)-3984)United States Atomic Energy Commission (Contract AT(30-1)-1842)National Science Foundation (Grant G-9330)United States Air Force, Air Force Cambridge Research Center (Contract AF19(604)-4551)United States Air Force, Air Force Cambridge Research Center, Air Research and Development Command (Contract AF19(604)-5992