Editorial: Pathogenesis, treatment, and future directions for rare T-cell leukemias

Mature T-cell leukemias represent rare, but increasingly recognized diseases of which, compared to their B-cell counterparts, comparatively little is established on their pathogenesis, diagnosis, and treatment. These leukemic post-thymic T-cell neoplasms range from the spectrum of chronic, sometimes debilitating disorders such as T-large granular lymphocytic leukemia (T-LGLL), and related leukemias such as NKLGLL, to more aggressive malignancies such as T- prolymphocytic leukemia (T-PLL). In this series, entitled ‘Pathogenesis, Treatment, and Future Directions for Rare T-cell Leukemias’ we review the current state of the science of these important T-cell neoplasms to inform on their treatment, diagnosis, and pathophysiology

CLEAR I: Ages and Metallicities of Quiescent Galaxies at 1.0<z<1.8\mathbf{1.0 < z < 1.8} Derived from Deep Hubble Space Telescope Grism Data

We use deep \textit{Hubble Space Telescope} spectroscopy to constrain the metallicities and (\editone{light-weighted}) ages of massive ($\log M_\ast/M_\odot\gtrsim10$) galaxies selected to have quiescent stellar populations at $1.0<z<1.8$. The data include 12--orbit depth coverage with the WFC3/G102 grism covering $\sim$ $8,000<\lambda<11,500$~\AA\, at a spectral resolution of $R\sim 210$ taken as part of the CANDELS Lyman-$\alpha$ Emission at Reionization (CLEAR) survey. At $1.0<z<1.8$, the spectra cover important stellar population features in the rest-frame optical. We simulate a suite of stellar population models at the grism resolution, fit these to the data for each galaxy, and derive posterior likelihood distributions for metallicity and age. We stack the posteriors for subgroups of galaxies in different redshift ranges that include different combinations of stellar absorption features. Our results give \editone{light-weighted ages of $t_{z \sim 1.1}= 3.2\pm 0.7$~Gyr, $t_{z \sim 1.2}= 2.2\pm 0.6$~Gyr, $t_{z\sim1.3}= 3.1\pm 0.6$~Gyr, and $t_{z\sim1.6}= 2.0 \pm 0.6$~Gyr, \editone{for galaxies at $z\sim 1.1$, 1.2, 1.3, and 1.6. This} implies that most of the massive quiescent galaxies at $168$\% of their stellar mass by a redshift of $z>2$}. The posteriors give metallicities of \editone{$Z_{z\sim1.1}=1.16 \pm 0.29$~$Z_\odot$, $Z_{z\sim1.2}=1.05 \pm 0.34$~$Z_\odot$, $Z_{z\sim1.3}=1.00 \pm 0.31$~$Z_\odot$, and $Z_{z\sim1.6}=0.95 \pm 0.39$~$Z_\odot$}. This is evidence that massive galaxies had enriched rapidly to approximately Solar metallicities as early as $z\sim3$.Comment: 32 pages, 23 figures, Resubmited to ApJ after revisions in response to referee repor

CLEAR: The Gas-Phase Metallicity Gradients of Star-Forming Galaxies at 0.6 < z < 2.6

We report on the gas-phase metallicity gradients of a sample of 264 star-forming galaxies at 0.6 < z < 2.6, measured through deep near-infrared Hubble Space Telescope slitless spectroscopy. The observations include 12-orbit depth Hubble/WFC3 G102 grism spectra taken as a part of the CANDELS Lya Emission at Reionization (CLEAR) survey, and archival WFC3 G102+G141 grism spectra overlapping the CLEAR footprint. The majority of galaxies (84%) in this sample are consistent with a zero or slightly positive metallicity gradient across the full mass range probed (8.5 < log M_*/M_sun < 10.5). We measure the intrinsic population scatter of the metallicity gradients, and show that it increases with decreasing stellar mass---consistent with previous reports in the literature, but confirmed here with a much larger sample. To understand the physical mechanisms governing this scatter, we search for correlations between the observed gradient and various stellar population properties at fixed mass. However, we find no evidence for a correlation with the galaxy properties we consider---including star-formation rates, sizes, star-formation rate surface densities, and star-formation rates per gravitational potential energy. We use the observed weakness of these correlations to provide material constraints for predicted intrinsic correlations from theoretical models.Comment: 19 pages, 10 figures (v2: typo fixed in Figure 10 label); submitted to Ap

CANDELS: The progenitors of compact quiescent galaxies at z~2

We combine high-resolution HST/WFC3 images with multi-wavelength photometry to track the evolution of structure and activity of massive (log(M*) > 10) galaxies at redshifts z = 1.4 - 3 in two fields of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). We detect compact, star-forming galaxies (cSFGs) whose number densities, masses, sizes, and star formation rates qualify them as likely progenitors of compact, quiescent, massive galaxies (cQGs) at z = 1.5 - 3. At z > 2 most cSFGs have specific star-formation rates (sSFR = 10^-9 yr^-1) half that of typical, massive SFGs at the same epoch, and host X-ray luminous AGN 30 times (~30%) more frequently. These properties suggest that cSFGs are formed by gas-rich processes (mergers or disk-instabilities) that induce a compact starburst and feed an AGN, which, in turn, quench the star formation on dynamical timescales (few 10^8 yr). The cSFGs are continuously being formed at z = 2 - 3 and fade to cQGs by z = 1.5. After this epoch, cSFGs are rare, thereby truncating the formation of new cQGs. Meanwhile, down to z = 1, existing cQGs continue to enlarge to match local QGs in size, while less-gas-rich mergers and other secular mechanisms shepherd (larger) SFGs as later arrivals to the red sequence. In summary, we propose two evolutionary scenarios of QG formation: an early (z > 2), fast-formation path of rapidly-quenched cSFGs that evolve into cQGs that later enlarge within the quiescent phase, and a slow, late-arrival (z < 2) path for SFGs to form QGs without passing through a compact state.Comment: Submitted to the Astrophysical Journal Letters, 6 pages, 4 figure

High-Resolution Near-Infrared Spectroscopy of an Equivalent Width-Selected Sample of Starbursting Dwarf Galaxies

Spectroscopic observations from the Large Binocular Telescope and the Very Large Telescope reveal kinematically narrow lines (approx. 50 km/s) for a sample of 14 Extreme Emission Line Galaxies (EELGs) at redshifts 1.4 < zeta < 2.3. These measurements imply that the total dynamical masses of these systems are low ( 3 10(exp 9) M). Their large [O III]5007 equivalent widths (500 1100 A) and faint blue continuum emission imply young ages of 10100 Myr and stellar masses of 10(exp 8)10(exp 9) M, confirming the presence of a violent starburst. The stellar mass formed in this vigorous starburst phase thus represents a large fraction of the total (dynamical) mass, without a significantly massive underlying population of older stars. The occurrence of such intense events in shallow potentials strongly suggests that supernova-driven winds must be of critical importance in the subsequent evolution of these systems

Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133605/1/bjh14046.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133605/2/bjh14046_am.pd

Allogeneic Transplantation Provides Durable Remission in a Subset of DLBCL Patients Relapsing after Autologous Transplantation

For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT

Targeted Therapy with Nanatinostat and Valganciclovir in Recurrent EBV-Positive Lymphoid Malignancies: A Phase 1b/2 Study

Lymphomas are not infrequently associated with the Epstein-Barr virus (EBV), and EBV positivity is linked to worse outcomes in several subtypes. Nanatinostat is a class-I selective oral histone deacetylase inhibitor that induces the expression of lytic EBV BGLF4 protein kinase in EBV+ tumor cells, activating ganciclovir via phosphorylation, resulting in tumor cell apoptosis. This phase 1b/2 study investigated the combination of nanatinostat with valganciclovir in patients aged ≥18 years with EBV+ lymphomas relapsed/refractory to ≥1 prior systemic therapy with no viable curative treatment options. In the phase 1b part, 25 patients were enrolled into 5 dose escalation cohorts to determine the recommended phase 2 dose (RP2D) for phase 2 expansion. Phase 2 patients (n = 30) received RP2D (nanatinostat 20 mg daily, 4 days per week with valganciclovir 900 mg orally daily) for 28-day cycles. The primary end points were safety, RP2D determination (phase 1b), and overall response rate (ORR; phase 2). Overall, 55 patients were enrolled (B-non-Hodgkin lymphoma [B-NHL], [n = 10]; angioimmunoblastic T-cell lymphoma-NHL, [n = 21]; classical Hodgkin lymphoma, [n = 11]; and immunodeficiency-associated lymphoproliferative disorders, [n = 13]). The ORR was 40% in 43 evaluable patients (complete response rate [CRR], 19% [n = 8]) with a median duration of response of 10.4 months. For angioimmunoblastic T-cell lymphoma-NHL (n = 15; all refractory to the last prior therapy), the ORR/CRR ratio was 60%/27%. The most common adverse events were nausea (38% any grade) and cytopenia (grade 3/4 neutropenia [29%], thrombocytopenia [20%], and anemia [20%]). This novel oral regimen provided encouraging efficacy across several EBV+ lymphoma subtypes and warrants further evaluation; a confirmatory phase 2 study (NCT05011058) is underway. This phase 1b/2 study is registered at www.clinicaltrials.gov as #NCT03397706

The CANDELS/SHARDS multiwavelength catalog in GOODS-N : photometry, photometric redshifts, stellar masses, emission-line fluxes, and star formation rates

We present a WFC3 F160W (H-band) selected catalog in the CANDELS/GOODS-N field containing photometry from the ultraviolet (UV) to the far-infrared (IR), photometric redshifts, and stellar parameters derived from the analysis of the multiwavelength data. The catalog contains 35,445 sources over the 171 arcmin(2) of the CANDELS F160W mosaic. The 5 sigma detection limits (within an aperture of radius 0 ''.17) of the mosaic range between H = 27.8, 28.2, and 28.7 in the wide, intermediate, and deep regions, which span approximately 50%, 15%, and 35% of the total area. The multiwavelength photometry includes broadband data from the UV (U band from KPNO and LBC), optical (HST/ACS F435W, F606W, F775W, F814W, and F850LP), near-to-mid IR (HST/WFC3 F105W, F125W, F140W, and F160W; Subaru/MOIRCS Ks; CFHT/Megacam K; and Spitzer/IRAC 3.6, 4.5, 5.8, and 8.0 mu m), and far-IR (Spitzer/MIPS 24 mu m, HERSCHEL/PACS 100 and 160 mu m, SPIRE 250, 350 and 500 mu m) observations. In addition, the catalog also includes optical medium-band data (R similar to 50) in 25 consecutive bands, lambda = 500-950 nm, from the SHARDS survey and WFC3 IR spectroscopic observations with the G102 and G141 grisms (R similar to 210 and 130). The use of higher spectral resolution data to estimate photometric redshifts provides very high, and nearly uniform, precision from z = 0-2.5. The comparison to 1485 good-quality spectroscopic redshifts up to z similar to 3 yields Delta z/(1 + z(spec)) = 0.0032 and an outlier fraction of eta = 4.3%. In addition to the multiband photometry, we release value-added catalogs with emission-line fluxes, stellar masses, dust attenuations, UV- and IR-based star formation rates, and rest-frame colors

Myeloid neoplasm with histiocytosis and spleen tyrosine kinase fusion responds to fostamatinib

Not available