Precise determination of primary cytogenetic abnormalities provides added value for stratification of chronic lymphocytic leukemia patients.

Cytogenetic analysis has become a standard procedure in the management of newly diagnosed chronic lymphocytic leukemia patients. Prognostic information is reported based on the presence of certain abnormalities and karyotype complexity after conventional karyotyping and/or fluorescence in situ hybridization (FISH). The information on cytogenetic abnormalities occurring in isolation is robust; however, the performance of patients with two or more cytogenetic abnormalities is heterogeneous and information is scarce. This retrospective study analyzed whether information on the precise determination of primary cytogenetic abnormalities can have some added value in terms of risk stratification in chronic lymphocytic leukemia (CLL) patients. The study cohort was 121 patients without the need to start treatment for CLL immediately after diagnosis but had completed initial cytogenetic analysis. Results from conventional karyotyping after stimulation of CLL cells and FISH analysis were combined. Risk stratification based purely on the determination of primary cytogenetic abnormalities was effective in CLL patients, with comparable results in stratification based on the presence of certain abnormalities and karyotype complexity. It is recommended that information on suspected primary abnormalities is included in cytogenetic reports, especially in patients with two or more abnormalities, because this can provide valuable additional information.

Allogeneic stem cell transplantation can improve outcome of AML patients without complete cytogenetic response after induction and consolidation treatment.

UNLABELLED: Our retrospective analysis was performed on 376 consecutive patients diagnosed with AML. A total of 256 (68%) were treated with standard "7+3" induction and high-dose cytarabine and mitoxantrone containing "4+3" consolidation/intensification regimens. Our study focused on patients with presumably very poor prognosis - patients, who did not achieve complete cytogenetic remission (CRc). Twenty-five AML patients without CRc were further analysed for clinical and laboratory parameters. Firstly, the subgroups with or without morphologic CR were compared. Similar cytogenetic abnormalities were observed in both with myelodysplasia related changes being the most common. Complex karyotype with deletion of 5q constituted approximately a third of all karyotypes in both subgroups. There were 1 patient with intermediate risk cytogenetics in the subgroup without morphologic CR and 5 patients in the subgroup with morphologic CR. Interestingly, in 4/25 patients subclones were diminished by the chemotherapy treatment, however cytogenetically less advanced clones proliferated. Secondly, transplanted or nontransplanted patients were analysed. Allogeneic stem cell transplantation (allo-SCT) was found to be the only curative treatment for patients without CRc after 7+3 and 4+3 regimens. In our cohort, 40% of the patients, who underwent allo-SCT, are alive. Importantly, 67% of the patients, who died after allo-SCT, died of causes unrelated to progression of AML. Nonrelapse mortality is therefore one of the fields where survival could be further improved. KEYWORDS: acute myeloid leukaemia, complete cytogenetic remission, cytogenetic abnormalities, stem cell transplantation, nonrelapse mortality.

The association of factor V Leiden with various clinical patterns of venous thromboembolism-the factor V Leiden paradox.

BACKGROUND: Factor V Leiden (FVL) supposedly carries relatively higher risk of deep vein thrombosis (DVT), compared to the risk of pulmonary embolism (PE). AIM: To prove this paradox in a group of patients with various clinical presentation of venous thromboembolism (VTE). MATERIALS AND METHODS: We retrospectively evaluated clinical pattern of VTE in patients who had been referred to vascular clinic shortly after an acute VTE event. In FVL positive and FVL negative groups we compared the prevalence of isolated symptomatic DVT (proximal or distal) and symptomatic PE with/without DVT, and, moreover, asymptomatic DVT or PE. RESULTS: Of 575 patients (mean age 57 years, 50.1% women), 120 were FVL positive and those had significantly higher prevalence of isolated symptomatic DVT, compared to symptomatic PE with/without DVT. Proximal DVT location was significantly more frequent in FVL carriers. The prevalence of asymptomatic PE did not differ between the two groups. The rate of asymptomatic DVT tended to be higher in FVL negative group. In a multivariate analysis, we confirmed FVL to be positively associated with isolated DVT presentation (odds ratio OR 1.757; 95% confidence interval (CI) 1.148-2.690). On the contrary, increasing age and unprovoked nature of VTE event carried a higher risk of symptomatic PE. CONCLUSIONS: We confirmed FVL to be significantly associated with isolated symptomatic DVT despite higher prevalence of proximal DVT in FVL carriers. The fact of relatively lower risk of PE in FVL positive patients might have clinical implication. However, mechanisms of FVL paradox remain to be elucidated.

Deep vein thrombosis and/or pulmonary embolism concurrent with superficial vein thrombosis of the legs: cross-sectional single center study of prevalence and risk factors.

AIM: The aim of this paper was to assess the prevalence of concurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the patients with superficial vein thrombosis (SVT) of the legs and to find factors significantly and independently associated with coincident DVT/PE. METHODS: In the setting of a tertiary referral hospital, patients with SVT, attending vascular clinic, underwent physical examination, laboratory testing and leg vein ultrasound (in the case of clinically suspected PE also perfusion/ventilation lung scan or/and helical CT pulmonary angiography). In statistical analysis, we used unpaired t-test, non-parametric Wilcoxon rank sum test, stepwise logistic regression and multivariable logistic regression model. RESULTS: We examined 138 patients (age 61.4 ± 13.9 years, 36.2% men), with ST mostly on varicose veins (89.9%). The prevalence of concurrent DVT/PE was 34.1%. Neither the clinical manifestation nor SVT localization differed significantly between the group with isolated SVT and that with coincident DVT/PE. Of all the assessed patients characteristics (age and sex, BMI, history of SVT, DVT or PE, hypercoagulable states, cardiovascular risk factors) only two factors were significantly and independently associated with the presence of concurrent DVT/PE. Log BMI was significantly higher in the patients with isolated SVT. Factor V Leiden (FVL) was proved as an independent risk factor for concomitant DVT/PE with odds ratio 2,531 (95% CI 1,064-6,016). CONCLUSION: The prevalence of concurrent DVT/PE in patients with SVT, referred to hospital vascular clinic was 34.1%. Lower BMI (log BMI, respectively) and the presence of FVL were significantly and independently associated with concurrent DVT/PE. Our results should be further investigated in a larger prospective study.

Leukaemia inhibitory factor (LIF) gene mutations in women diagnosed with unexplained infertility and endometriosis have a negative impact on the IVF outcome. A pilot study.

The frequency of functionally relevant mutations of the leukaemia inhibitory factor (LIF) gene in infertile women is significantly enhanced in comparison with fertile controls. The objective of this retrospective cohort study was to evaluate the impact of LIF gene mutations on the outcome of the treatment in women with various causes of infertility. Fifteen infertile women with the G to A transition at position 3400 leading to the valine to methionine exchange at codon 64 were analysed. Group A was made up of women with diagnoses that are frequently accompanied by changes in humoral as well as cell-mediated immunity - idiopathic infertility and endometriosis (N = 7). Group B consisted of patients with polycystic ovary syndrome (PCOS), andrological factor, tubal factor and hyperprolactinaemia (N = 8). The control group comprised 136 infertile women with no LIF gene mutation diagnosed with idiopathic infertility and endometriosis (N = 37) (group C) and patients with PCOS, tubal and andrological factor (N = 99) (group D). Seven of the mutation-positive patients were successfully treated by in vitro fertilization (IVF), but nobody in this group was diagnosed with idiopathic infertility and only one with endometriosis, which means that there is a statistically significant difference in the pregnancy rates between groups A and B (P = 0.01, Fisher's 2 by 2 exact test) but no statistically significant difference when comparing patients with the LIF gene mutation (group A+B) to no LIF gene mutation (group C+D). The results suggest that in mutation-positive women the idiopathic infertility and endometriosis have a negative impact on the outcome of IVF treatment.

[Monitoring of haemocoagulative changes during long-term doses of low molecular weight heparin during pregnancy]. / Sledování hemokoagulacních zmen v prubehu tehotenství zen s opakovaným potrácením v závislosti na podávání nízkomolekulárního heparinu.

OBJECTIVE: The aim of study was to compare plasma levels of selected coagulation parameters in pregnant women with long-term administration of low molecular weight heparin (LMWH) versus cohort of healthy women LMWHs untreated. DESIGN: Prospective study. SETTING: Department of Haematology, Institute of Clinical Biochemistry and Haematology, Charles University and University Hospital, Plzen. METHODS: We examined 67 pregnant women with recurrent fetal loss in previous pregnant history treated by long-term prophylactic administration of LMWH. Blood samples were collected before gestation and at 10th, 20th, 30th gestational weeks. RESULTS: Pregnant women with own history of recurrent fetal loss treated by the long-term prophylactic dose of LMWHs during pregnancy have the same values of the coagulation parameters as the control cohort in spite of fact that the clinical efficacy of administered LMWHs is high. CONCLUSION: Our results suggest that heparin may act by many unknown different mechanisms, such as inhibition of complement binding or secretion of prostaglandins.

[Chromosome aberrations in the etiology of abortions after infertility treatment using IVF and ET]. / Chromosomální aberace v etiologii potratu po lécbe sterility metodou IVF a ET.

Chromosomal aberrations are a frequent cause of miscarriages during the first trimester of gestation. The most frequent finding in the authors group was trisomy 16 (in five patients). After extracorporeal fertilization (IVF) the percentage of abnormal karyotypes does not increase, the main risk factor being the women's age.

[Screening for fragile X syndrome in handicapped boys]. / Screenings auf das Syndrom fragiles X bei behinderten Knaben.

From a group of 201 mentally retarded boys 149 were clinically and somatometrically examined. Chromosomal analysis for detection of a fra(X)-syndrome was undertaken, when more than 3 of the chosen examination parameters were suspicious or when anamnestic clues for X-chromosomally linked mental retardation were present. 89 boys fulfilled above requirements, 14 of these had a fra(X)-syndrome (15.7%). The following symptoms were found with outstanding frequency: hyperactivity, hypotonic muscles, enlargement of testes, increased length of hands, retarded development of speech, dermatoglyphic abnormalities. If more than 3 of these findings occur, a chromosomal analysis for exclusion of a fra(X)-syndrome should be performed.

45,X/47,XYY mosaicism: clinical discrepancy between prenatally and postnatally diagnosed cases.

45,X/47,XYY mosaicism is a rare chromosomal disorder with clinical information limited to 11 postnatal cases in the literature and with uncertainty regarding prenatal prediction of phenotype and prognosis. We report on 7 new cases of 45,X/47,XYY mosaicism, three detected prenatally and 4 diagnosed postnatally. A clinical comparison of the cases of 45,X/47,XYY mosaicism is presented together with a literature review.

Familial translocation t(17;22), including the segregation in five consecutive abortuses.

A cytogenetic study of a family with t(17;22) is presented. The translocation has been detected in four generations. The proband was a female who has had ten pregnancies, seven of which had resulted in spontaneous abortion. The material of five aborted fetuses was available for cytogenetic examination. The karyotypes revealed four different forms of chromosomal imbalance, most of them due to 3:1 segregation. The only living proband's offspring was born after amniocentesis and had a balanced translocation t(17;22).

Y;autosome translocations and mosaicism in the aetiology of 45,X maleness: assignment of fertility factor to distal Yq11.

Three 45,X males have been studied with Y-DNA probes by Southern blotting and in situ hybridization. Southern blotting studies with a panel of mapped Y-DNA probes showed that in all three individuals contiguous portions of the Y chromosome including all of the short arm, the centromere, and part of the euchromatic portion of the long arm were present. The breakpoint was different in each case. The individual with the largest portion (intervals 1-6) is a fertile male belonging to a family in which the translocation is inherited in four generations. The second adult patient, who has intervals 1-5, is an azoospermic, sterile male. These phenotypic findings suggest the existence of a gene involved in spermatogenesis in interval 6 in distal Yq11. The third case, a boy with penoscrotal hypospadias, has intervals 1-4B. In situ hybridization with the pseudoautosomal probe pDP230 and the Y chromosome specific probe pDP105 showed that Y-derived DNA was translocated onto the short arm of a chromosome 15, 14, and 14, respectively. One of the patients was a mosaic for the 14p+ translocation chromosome. Our data and those reported by others suggest the following conclusions based on molecular studies in eight 45,X males: The predominant aetiological factor is Y;autosome translocation observed in seven of the eight cases. As the remaining case was a low-grade mosaic involving a normal Y chromosome, the maleness in all cases was due to the effect of the testis determining factor, TDF. There is preferential involvement of the short arm of an acrocentric chromosome (five out of seven translocations) but other autosomal regions can also be involved. The reason why one of the derivative translocation chromosomes becomes lost may be that it has no centromere.

Frequency of tri- and multiradial configurations in fragile X chromosomes.

The appearance of tri- or multiradial configurations in fragile chromosomes is affected by the number of cell cycles in the folate antagonist system. In this study the lymphocytes were incubated for 96 h in a medium 199 without calf serum, and tri- or multiradial configurations were observed in 6 of 12 cases of fra(X) chromosome. The frequency ranged from 0.6% to 7.4% of fra(X) chromosomes.