Results of an Early Access Treatment Protocol of Daratumumab Monotherapy in Spanish Patients With Relapsed or Refractory Multiple Myeloma

Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16 mg/kg) was administered to 73 patients who had >= 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03-13.17) months, with a median number of 12 (range: 1-25) infusions. Grade 3/4 treatment-emergent adverse events were reported in 74% of patients and included lymphopenia (28.8%), thrombocytopenia (27.4%), neutropenia (21.9%), leukopenia (19.2%), and anemia (15.1%). Common (>5%) serious treatmentemergent adverse events included respiratory tract infection (9.6%), general physical health deterioration (6.8%), and back pain (5.5%). Infusion-related reactions occurred in 45% of patients. The median change from baseline in all domains of the EQ-5D-5L and EORTC QLQ-C30 was mostly 0. A total of 18 (24.7%) patients achieved a partial response or better, with 10 (13.7%) patients achieving a very good partial response or better. Median progression-free survival was 3.98 months. The results of this early access treatment protocol are consistent with previously reported trials of daratumumab monotherapy and confirm its safety and antitumoral efficacy in Spanish patients with heavily treated relapsed or refractory multiple myeloma

Impact of female age and male infertility on ovarian reserve markers to predict outcome of assisted reproduction technology cycles

<p>Abstract</p> <p>Background</p> <p>This study was designed to assess the capability of ovarian reserve markers, including baseline FSH levels, baseline anti-Müllerian hormone (AMH) levels, and antral follicle count (AFC), as predictors of live births during IVF cycles, especially for infertile couples with advanced maternal age and/or male factors.</p> <p>Methods</p> <p>A prospective cohort of 336 first IVF/ICSI cycles undergoing a long protocol with GnRH agonist was investigated. Patients with endocrine disorders or unilateral ovaries were excluded.</p> <p>Results</p> <p>Among the ovarian reserve tests, AMH and age had a greater area under the receiving operating characteristic curve than FSH in predicting live births. Furthermore, AMH and age were the sole predictive factors of live births for women greater than or equal to 35 years of age; while AMH was the major determinant of live births for infertile couples with absence of male factors by multivariate logistic regression analysis. However, all the studied ovarain reserve tests were not preditive of live births for women < 35 years of age or infertile couples with male factors.</p> <p>Conclusion</p> <p>The serum AMH levels were prognostic for pregnancy outcome for infertile couples with advanced female age or absence of male factors. The predictive capability of ovarian reserve tests is clearly influenced by the etiology of infertility.</p

THE MASSES OF LOCAL GROUP DWARF SPHEROIDAL GALAXIES: THE DEATH OF THE UNIVERSAL MASS PROFILE

We investigate the claim that all dwarf spheroidal galaxies (dSphs) reside within halos that share a common, universal mass profile as has been derived for dSphs of the galaxy. By folding in kinematic information for 25 Andromeda dSphs, more than doubling the previous sample size, we find that a singular mass profile cannot be found to fit all of the observations well. Further, the best-fit dark matter density profile measured solely for the Milky Way dSphs is marginally discrepant with that of the Andromeda dSphs (at just beyond the 1σ level), where a profile with lower maximum circular velocity, and hence mass, is preferred. The agreement is significantly better when three extreme Andromeda outliers, And XIX, XXI, and XXV, all of which have large half-light radii (600 pc) and low-velocity dispersions (σv < 5 km s−1), are omitted from the sample. We argue that the unusual properties of these outliers are likely caused by tidal interactions with the host galaxy

THE MASSES OF LOCAL GROUP DWARF SPHEROIDAL GALAXIES: THE DEATH OF THE UNIVERSAL MASS PROFILE

We investigate the claim that all dwarf spheroidal galaxies (dSphs) reside within halos that share a common, universal mass profile as has been derived for dSphs of the galaxy. By folding in kinematic information for 25 Andromeda dSphs, more than doubling the previous sample size, we find that a singular mass profile cannot be found to fit all of the observations well. Further, the best-fit dark matter density profile measured solely for the Milky Way dSphs is marginally discrepant with that of the Andromeda dSphs (at just beyond the 1σ level), where a profile with lower maximum circular velocity, and hence mass, is preferred. The agreement is significantly better when three extreme Andromeda outliers, And XIX, XXI, and XXV, all of which have large half-light radii (600 pc) and low-velocity dispersions (σv < 5 km s−1), are omitted from the sample. We argue that the unusual properties of these outliers are likely caused by tidal interactions with the host galaxy

The Sagittarius Streams in the Southern Galactic Hemisphere

The structure of the Sagittarius stream in the Southern Galactic hemisphere is analysed with the Sloan Digital Sky Survey Data Release 8. Parallel to the Sagittarius tidal track, but ~ 10deg away, there is another fainter and more metal-poor stream. We provide evidence that the two streams follow similar distance gradients but have distinct morphological properties and stellar populations. The brighter stream is broader, contains more metal-rich stars and has a richer colour-magnitude diagram with multiple turn-offs and a prominent red clump as compared to the fainter stream. Based on the structural properties and the stellar population mix, the stream configuration is similar to the Northern "bifurcation". In the region of the South Galactic Cap, there is overlapping tidal debris from the Cetus Stream, which crosses the Sagittarius stream. Using both photometric and spectroscopic data, we show that the blue straggler population belongs mainly to Sagittarius and the blue horizontal branch stars belong mainly to the Cetus stream in this confused location in the halo

Therapy-Related Myeloid Neoplasms in Patients With Acute Promyelocytic Leukemia Treated With All-Trans-Retinoic Acid and Anthracycline-Based Chemotherapy

Purpose We analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR). Patients and Methods From 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Espanol para el Tratamiento de Enfermedades Hematologicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy. Results Seventeen of 918 patients who achieved CR developed t-MN (10 with = 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months. Conclusion t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted

Serum Anti-müllerian hormone, follicle stimulating hormone and antral follicle count measurement cannot predict pregnancy rates in IVF/ICSI cycles

PURPOSE: To investigate whether serum anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), or antral follicle count (AFC) are predictive for clinical pregnancy in in vitro fertilization (IVF) patients. METHODS: Serum AMH, inhibin B, FSH, luteinizing hormone (LH), estradiol (E2), prolactin, and thyroid stimulating hormone (TSH) levels and AFC of 189 women under 40 years of age were investigated. Pregnant and non-pregnant women were compared. RESULTS: Forty-seven (24.8 %) clinical pregnancies were observed in 189 women. There was no significant difference in terms of mean age, duration of infertility, body mass index, AMH, LH, FSH, E2, TSH, Inhibin B, AFC and total oocyte number between women who did and who did not become pregnant. Additionally, there was no significant difference in clinical pregnancy rates between the quartiles of AMH, FSH and AFC. (P values were 0.668, 0.071, and 0.252, respectively.) CONCLUSION: Serum AMH and FSH, and AFC cannot predict clinical pregnancy in IVF patients under 40; the pregnancy rate tends to increase as AMH increases, although this remains non-significant