A modified integrated genetic model for risk prediction in younger patients with acute myeloid leukemia

Background: Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice. Methods and Findings: We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0.919). Conclusions: The IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy

Continuous combined HRT in post-menopause: two regimen comparative study

Continuous combined HRT in post-menopause: two regimen comparative study U. Omodei, F. Sorgi, A. Torri and AM Boccuti Department of Obstetrics and Gynecology, University of Brescia, Italy Introduction A large body of evidence has accumulated concerning the positive benefits of estrogen treatment, including a decreased incidence of osteoporosis, vasomotor symptomathology, and relative risk of chardiovascular disease (CHD)

A New HRT Regimen Using Estradiol Valerate and Cyproterone Acetate: Impact on Lipid Metabolism

We evaluated a new sequential HRT regimen (Climen‐Schering) consisting of a combination of estradiol valerate (2 mg, days 1‐11) and cyproterone acetate (CPA: 1 mg) plus estradiol valerate (2 mg, days 12‐21) followed by a 7‐day interval with no drug intake. The interesting aspect of this regimen is the use of CPA. a strong progestogen with antiandrogenic properties. For this reason, CPA is expected not to counteract the favourable estrogen impact on lipids

A New HRT Regimen Using Estradiol Valerate and Cyproterone Acetate: Clinical Data

A new sequential HRT regimen (Climen‐Schering) consisting of a combination of estradiol valerate (EV)(2 mg. days 1‐11) and cyproterone acetate (CPA; 1 mg) plus EV (2 mg, days 12‐ 21) followed by a 7‐day drug‐free interval was tested, The interesting aspect of this regimen is the use of CPA, a strong progestogen with antiandrogenic properties

Endometrial ultrasound transvaginal (TVU) assessment in postmenopausal women on hormone replacement therapy (HRT)

There are only fragmentary data about TVU assessment in postmenopausal women on HRT, but usually an endometrial thickness (ET)< 4mm (as for postmenopausal women not on HRT) seems adequate to exclude the presence of endometrial pathology. The aim of our study was to evaluate the TVU effectiveness compared with hysteroscopy (HSG) plus endometrial biopsy to identify endometrial alterations, and to find a cut-off value under which invasive techniques are useless

The Effect of HRT on Endometrial Thickness (ET) and Uterine Arterial Blood Flow Assessed by Transvaginal Ultrasound (TVU).

The aim of our study was to evaluate the TVU effectiveness compared to hysteroscopy plus endometrial biopsy (HS/B) to identity endometrial alterations and to find a cut‐off value under which invasive techniques are useless; furthermore, we aimed to determine whether HRT had any positive effect on uterine arterial blood flow, 96 postmenopausal women (pmw) consented to enter the study. Patients*(pts) mean age was 56.1 years. with menopausal amenorrhoea for at least 9 months and on HRT for at least 6 month

The effect of HRT on uterine arterial blood flow in postmenopausal women assessed by transvaginal color doppler sonography (TVDS)

HRT has been suggested to have neither a metabolic nor a direct vascular effect on arterial tone. PI and RI are indicators of resistance to flow: the higher the value of these indices, the greater the resistance to flow. The TVDS measurements of uterine blood flow in postmenopausal women (pmw) show a mean uterine artery PI of 3.3+/-1.04 and a mean RI of 0.93+/-0.1. The aim of our study was to determine whether HRT had any positive effect on uterine arterial blood flow. 96 pmw consented to enter the study

The effect of HRT on uterine arterial blood flow in postmenopausal women assessed by transvaginal color doppler sonography (TVDS)

HRT has been suggested to have neither a metabolic nor a direct vascular effect on arterial tone. PI and RI are indicators of resistance to flow: the higher the value of these indices, the greater the resistance to flow. The TVDS measurements of uterine blood flow in postmenopausal women (pmw) show a mean uterine artery PI of 3.3+/-1.04 and a mean RI of 0.93+/-0.1. The aim of our study was to determine whether HRT had any positive effect on uterine arterial blood flow

Endometrial ultrasound transvaginal (TVU) assessment in postmenopausal women on hormone replacement therapy (HRT)

There are only fragmentary data about TVU assessment in postmenopausal women on HRT, but usually an endometrial thickness (ET)< 4mm (as for postmenopausal women not on HRT) seems adequate to exclude the presence of endometrial pathology. The aim of our study was to evaluate the TVU effectiveness compared with hysteroscopy (HSG) plus endometrial biopsy to identify endometrial alterations, and to find a cut-off value under which invasive techniques are useless