The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is ...achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
Context.More than ten Centaurs are now known to have cometary activity at large heliocentric distance (i.e. $\simeq$5-13 AU). Among these objects, 174P/Echeclus which showed cometary activity at ...13 AU from the Sun, is a unique case, because of: (i) the amplitude of its outburst, (ii) the source of cometary activity that appears distinct from Echeclus itself. Aims.This paper aims at investigating the physical conditions that have led to this unusual outburst. The purpose is also to quantify this phenomenon and to provide observational constraints for its modeling. Methods.We use observations from different telescopes, performed before, during, and after the outburst. We performed the main observations on March 23 and 30, 2006, with the 8.2-m ESO Very Large Telescope and FORS 1 instrument. They consist of visible images and spectra. Results.Our main results are: (i) a cometary source distinct from Echeclus itself that presents a brightness distribution compatible with a diffuse source; (ii) a total dust production rate Qdust$\simeq$ 86 kg s-1 and a parameter $Af\rho\simeq$ 10 000 cm; (iii) no emission lines (CN and C2) can be detected in the visible range; (iv) the upper limits for the CN and C2 production rates are $\simeq$3.8$\times$1025 and $\simeq$1026 molecules s-1 respectively; (v) we detected no Echeclus' satellite before the outburst up to MR $\simeq$ 26; (vi) the upper limit for the object generating the coma is about 8 km in diameter; (vi) and we detected no cometary activity one year later, in March 2007.
ABSTRACT
Comets are seen as depleted in nitrogen compared to the protosolar value, but a small number exhibit significantly higher than typical N2/CO ratios: C/1908 R1 (Morehouse), C/1940 R2 ...(Cunningham), C/1947 S1 (Bester), C/1956 R1 (Arend–Roland), C/1957 P1 (Mrkos), C/1961 R1 (Humason), C/1969 Y1 (Bennett), C/1973 E1 (Kohoutek), C/1975 V1-A (West), C/1986 P1 (Wilson), C/1987 P1 (Bradfield), C/2001 Q4 (NEAT), C/2002 VQ94 (LINEAR), C/2016 R2 (PanSTARRS), and periodic comets 1P/Halley, 29P/Schwassmann–Wachmann 1, and 67P/Churyumov–Gerasimenko. This study examines the composition and dynamical histories of these N2-‘rich’ comets to unearth insights into their formation processes. Using updated N2 fluorescence factors, we re-estimate the N2/CO ratios of this sample and find that they are consistent with the expected values for comets based on estimations of the protosolar nebula. These also often display larger nucleus sizes and show rapid tail morphology variations due to their ionic nature. Numerical simulations reveal no common dynamical history, suggesting that the N2/CO ratio is independent of the number of inner Solar System passages and that N2 is homogeneously distributed within these comets. These volatile-rich comets share an Oort Cloud origin which is consistent with their survival over the past 4.5 Gyr. Our study also suggests that there may be a bias using modern high-resolution spectrometers with narrow slits, which could potentially overlook the ion tail of comets. We advocate for the use of long-slit spectroscopy to potentially detect a wider range of N2-rich comets, thereby enriching our understanding of comet compositions and origins.
Aims.
2I/Borisov (hereafter 2I) is the first visibly active interstellar comet observed in the Solar System, allowing us for the first time to sample the composition of a building block from another ...system. We report on the monitoring of 2I with the Ultraviolet-Visual Echelle Spectrograph, the high-resolution optical spectrograph of the ESO Very Large Telescope at Paranal, for four months from November 15, 2019 to March 16, 2020. Our goal is to characterise the activity and composition of 2I with respect to Solar System comets.
Methods.
We collected high-resolution spectra at 12 different epochs from 2.1 au pre-perihelion to 2.6 au post-perihelion.
Results.
On December 24 and 26, 2019, close to perihelion, we detected several OH lines of the 309 nm (0–0) band and derived a water production rate of 2.2 ± 0.2 × 10
26
molecules s
−1
. The three OI forbidden oxygen lines were detected at different epochs and we derived a green-to-red doublet intensity ratio (G/R) of 0.31 ± 0.05 close to perihelion. The NH
2
ortho and para lines from various bands were measured and allowed us to derive an ortho-to-para abundance ratio (OPR) of 3.21 ± 0.15, corresponding to an OPR and spin temperature of ammonia of 1.11 ± 0.08 and 31
−5
+10
K, respectively. These values are consistent with the values usually measured for Solar System comets. Emission lines of the radicals NH (336 nm), CN (388 nm), CH (431 nm), and C
2
(517 nm) were also detected. Several FeI and NiI lines were identified and their intensities were measured to provide a ratio of log (NiI/FeI) = 0.21 ± 0.18, which is in agreement with the value recently found in Solar System comets.
Conclusions.
Our high spectral resolution observations of 2I/Borisov and the associated measurements of the NH
2
OPR and the Ni/Fe abundance ratio are remarkably similar to Solar System comets. Only the G/R ratio is unusually high, but it is consistent with the high abundance ratio of CO/H
2
O found by other investigators.
Context. Early observations of comet C/2016 R2 (PanSTARRS) have shown that the composition of this comet is very peculiar. Radio observations have revealed a CO-rich and HCN-poor comet and an optical ...coma dominated by strong emission bands of CO+ and, more surprisingly, N2+ $\mathrm{N_2^+}$ N2+ . Aims. The strong detection of N2+ $\mathrm{N_2^+}$N2+ in the coma of C/2016 R2 provided an ideal opportunity to measure the 14N∕15N isotopic ratio directly from N2+ $\mathrm{N_2^+}$N2+ for the first time, and to estimate the N2∕CO ratio, which is an important diagnostic to constrain formation models of planetesimals, in addition to the more general study of coma composition. Methods. We obtained high resolution spectra of the comet in February 2018 when it was at 2.8 au from the Sun. We used the UVES spectrograph of the European Southern Observatory Very Large Telescope, complemented with narrowband images obtained with the TRAPPIST telescopes. Results. We detect strong emissions from the N2+ $\mathrm{N_2^+}$N2+ and CO+ ions, but also CO2+ $\mathrm{CO_2^+}$CO2+ , emission lines from the CH radical, and much fainter emissions of the CN, C2, and C3 radicals that were not detected in previous observations of this comet. We do not detect OH or H2O+, and we derive an upper limit of the H2O+∕CO+ ratio of 0.4, implying that the comet has a low water abundance. We measure a N2+/CO+ $\mathrm{N_2^+/CO^+}$N2+/CO+ ratio of 0.06 ± 0.01. The non-detection of NH2 indicates that most of the nitrogen content of the comet is in N2. Together with the high N2+/CO+ $\mathrm{N_2^+/CO^+}$N2+/CO+ ratio, this could indicate a low formation temperature of the comet or that the comet is a fragment of a large differentiated Kuiper Belt object. The CO2+/CO+ $\mathrm{CO_2^+/CO^+}$CO2+/CO+ ratio is 1.1 ± 0.3. We do not detect 14N15N+ lines and can only put a lower limit on the 14N∕15N ratio (measured from N2+ $\mathrm{N_2^+}$N2+ ) of about 100, which is compatible with measurements of the same isotopic ratio for NH2 and CN in other comets. Finally, in addition to the OI and CI forbidden lines, we detect for the first time the forbidden nitrogen lines NI doublet at 519.79 and 520.03 nm in the coma of a comet.
We report the orbital distribution of the trans-Neptunian objects (TNOs) discovered during the Canada-France Ecliptic Plane Survey (CFEPS), whose discovery phase ran from early 2003 until early 2007. ...The follow-up observations started just after the first discoveries and extended until late 2009. We obtained characterized observations of 321 deg2 of sky to depths in the range g ~ 23.5-24.4 AB mag. We provide a database of 169 TNOs with high-precision dynamical classification and known discovery efficiency. Using this database, we find that the classical belt is a complex region with sub-structures that go beyond the usual splitting of inner (interior to 3:2 mean-motion resonance MMR), main (between 3:2 and 2:1 MMR), and outer (exterior to 2:1 MMR). The main classical belt (a = 40-47 AU) needs to be modeled with at least three components: the 'hot' component with a wide inclination distribution and two 'cold' components (stirred and kernel) with much narrower inclination distributions. The hot component must have a significantly shallower absolute magnitude (Hg ) distribution than the other two components. With 95% confidence, there are 8000+1800 --1600 objects in the main belt with Hg <= 8.0, of which 50% are from the hot component, 40% from the stirred component, and 10% from the kernel; the hot component's fraction drops rapidly with increasing Hg . Because of this, the apparent population fractions depend on the depth and ecliptic latitude of a trans-Neptunian survey. The stirred and kernel components are limited to only a portion of the main belt, while we find that the hot component is consistent with a smooth extension throughout the inner, main, and outer regions of the classical belt; in fact, the inner and outer belts are consistent with containing only hot-component objects. The Hg <= 8.0 TNO population estimates are 400 for the inner belt and 10,000 for the outer belt to within a factor of two (95% confidence). We show how the CFEPS Survey Simulator can be used to compare a cosmogonic model for the orbital element distribution to the real Kuiper Belt.
We report on photometry and high-resolution spectroscopy of the chemically peculiar Jupiter-family comet (hereafter JFC) 21P/Giacobini-Zinner. Comet 21P is a well-known member of the ...carbon-chain-depleted family, but also displays a depletion of amines. We continuously monitored the comet over more than seven months with the two TRAPPIST telescopes (TN and TS), covering a wide heliocentric distance range from 1.60 au inbound to 2.10 au outbound with a perihelion at 1.01 au on September 10, 2018. We computed and followed the evolution of the dust- (represented by
Afρ
) and gas-production rates of the daughter species OH, NH, CN, C
3
, and C
2
and their relative abundances to OH and to CN over the cometary orbit. We compared them to those measured in the previous apparitions. The activity of the comet and its water production rate reached a maximum of (3.72 ± 0.07) × 10
28
mol s
−1
on August 17, 2018 (
r
h
= 1.07 au), 24 days before perihelion. The peak value of
A
(0)
fρ
was reached on the same date (1646 ± 13) cm in the red filter. Using a sublimation model for the nucleus, we constrained the active surface of the nucleus using the slow-rotator model. The abundance ratios of the various species are remarkably constant over a wide range of heliocentric distances before and after perihelion, showing a high level of homogeneity of the ices in the surface of the nucleus. The behaviour and level of the activity of the comet is also remarkably similar over the last five orbits. In the coma dust colour, 21P shows reflective gradients similar to JFCs. We obtained a high-resolution spectrum of 21P with UVES at ESO Very Large Telescope one week after perihelion. Using the CN B-X (0, 0) violet band, we measured
12
C/
13
C and
14
N/
15
N isotopic ratios of 100 ± 10 and 145 ± 10, respectively, both in very good agreement with the ratios commonly found in comets. We measured an ortho-para abundance ratio of NH
3
of 1.16 ± 0.02, corresponding to a nuclear spin temperature of
T
spin
= 27 ± 1 K, which is similar to other comets. While the abundance ratios in the gaseous coma reveal a peculiar composition, the isotopic and ortho-to-para ratios appear entirely normal. We performed a dynamical simulation of 21P and found that it is likely a young member of the JFC population. We favour a pristine composition scenario to explain the chemical peculiarities of this comet.
Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after ...prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.
The N2 production rate in comet C/2016 R2 (PanSTARRS) Anderson, S E; Rousselot, P; Noyelles, B ...
Monthly notices of the Royal Astronomical Society,
10/2022, Letnik:
515, Številka:
4
Journal Article, Web Resource
Recenzirano
Odprti dostop
ABSTRACT
Observations of comet C/2016 R2 (PanSTARRS) have revealed exceptionally bright emission bands of N$_2^+$, the strongest ever observed in a comet spectrum. Alternatively, it appears to be ...poor in CN compared to other comets, and remarkably depleted in H2O. Here, we quantify the N2 production rate from N$_2^+$ emission lines using the Haser model. We derived effective parent and daughter scale lengths for N2 producing N$_2^+$. This is the first direct measurement of such parameters. Using a revised fluorescence efficiency for N$_2^+$, the resulting production rate of molecular nitrogen is inferred to be Q(N2) ∼ 1 × 1028 molecules s−1 on average for 2018 February 11, 12, and 13, the highest for any known comet. Based on a CO production rate of Q(CO) ∼ 1.1 × 1029 molecules s−1, we find Q(N2)/Q(CO) ∼ 0.09, which is consistent with the N$_2^+$/CO+ ratio derived from the observed intensities of N$_2^+$ and CO+ emission lines. We also measure significant variations in this production rate between our three observing nights, with Q(N2) varying by plus or minus 20 per cent according to the average value.
Tyrosine kinase inhibitors (TKIs) have potent effects on malignant cells, and they also target kinases in normal cells, which may have therapeutic implications. Using a collection of 55 leukemia ...patients treated with TKI therapy (chronic myeloid leukemia, n=47; acute lymphoblastic leukemia, n=8), we found that dasatinib, a second-generation broad-spectrum TKI, induced a rapid, dose-dependent and substantial mobilization of non-leukemic lymphocytes and monocytes in blood peaking 1-2 h after an oral intake and the blood counts closely mirrored drug plasma concentration. A preferential mobilization was observed for natural killer (NK), NK T, B and γδ+ T cells. Mobilization was coupled with a more effective transmigration of leukocytes through an endothelial cell layer and improved cytotoxicity of NK cells. Platelet numbers decreased markedly after the drug intake in a proportion of patients. Similar effects on blood cell dynamics and function were not observed with any other TKI (imatinib, nilotinib and bosutinib). Thus, dasatinib induces a unique, rapid mobilization and activation of cytotoxic, extravasation-competent lymphocytes, which may not only enhance antileukemia immune responses but can also be causally related to the side-effect profile of the drug (pleural effusions, thrombocytopenia).
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