A 15-Year Analysis of Early and Late Autologous Hematopoietic Stem Cell Transplant in Relapsed, Aggressive, Transformed, and Nontransformed Follicular Lymphoma

AbstractAutologous stem cell transplant (ASCT) has been shown to be an effective treatment for follicular lymphoma (FL). We explored our experience in ASCT for FL among all patients treated over a 15-year period from diagnosis through their entire treatment history including relapse post ASCT. All patients who underwent an unpurged ASCT for relapsed, advanced FL between June 1990 and December 2000 were analyzed. After salvage therapy they received melphalan/etoposide/total body irradiation, BCNU, etoposide, cytarabine, melphalan (BEAM), or cyclophosphamide BCNU etoposide (CBV) as conditioning for the ASCT. One hundred thirty-eight patients with a median age of 48 years and a median follow-up of 7.6 years were analyzed. The majority were of the subtype grade 1, nontransformed (FL-NT), having had 1 prior chemotherapy. The progression-free (PFS) and overall survival (OS) of the FL-NT at 10 years were 46% and 57%, respectively, and at 5 years for the transformed (FL-T) were 25% and 56%, respectively, of which only the PFS was significantly different (P = .007). The median OS from diagnosis was 16 years for the FL-NT. ASCT positively altered the trend of shorter remissions with subsequent chemotherapies, and there was no difference in OS between those who had 1, 2, or >2 chemotherapies prior to ASCT. Salvage therapy for relapse post ASCT was effective (OS >1 year) in a third of patients. Unpurged ASCT is an effective tool in the treatment of relapsed, aggressive FL-NT and FL-T, is superior to retreatment with standard chemotherapy, is effective at various stages of treatment, is likely to have a beneficial influence on the natural history of this disease, and the disease is amenable to salvage therapy post-ASCT relapse

Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL

Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS-International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell\u2012like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #NCT01287741

The ATLAS experiment at the CERN Large Hadron Collider: a description of the detector configuration for Run 3

The ATLAS detector is installed in its experimental cavern at Point 1 of the CERN Large Hadron Collider. During Run 2 of the LHC, a luminosity of ℒ = 2 × 1034 cm-2 s-1 was routinely achieved at the start of fills, twice the design luminosity. For Run 3, accelerator improvements, notably luminosity levelling, allow sustained running at an instantaneous luminosity of ℒ = 2 × 1034 cm-2 s-1, with an average of up to 60 interactions per bunch crossing. The ATLAS detector has been upgraded to recover Run 1 single-lepton trigger thresholds while operating comfortably under Run 3 sustained pileup conditions. A fourth pixel layer 3.3 cm from the beam axis was added before Run 2 to improve vertex reconstruction and b-tagging performance. New Liquid Argon Calorimeter digital trigger electronics, with corresponding upgrades to the Trigger and Data Acquisition system, take advantage of a factor of 10 finer granularity to improve triggering on electrons, photons, taus, and hadronic signatures through increased pileup rejection. The inner muon endcap wheels were replaced by New Small Wheels with Micromegas and small-strip Thin Gap Chamber detectors, providing both precision tracking and Level-1 Muon trigger functionality. Trigger coverage of the inner barrel muon layer near one endcap region was augmented with modules integrating new thin-gap resistive plate chambers and smaller-diameter drift-tube chambers. Tile Calorimeter scintillation counters were added to improve electron energy resolution and background rejection. Upgrades to Minimum Bias Trigger Scintillators and Forward Detectors improve luminosity monitoring and enable total proton-proton cross section, diffractive physics, and heavy ion measurements. These upgrades are all compatible with operation in the much harsher environment anticipated after the High-Luminosity upgrade of the LHC and are the first steps towards preparing ATLAS for the High-Luminosity upgrade of the LHC. This paper describes the Run 3 configuration of the ATLAS detector

Electron and photon efficiencies in LHC Run 2 with the ATLAS experiment

Precision measurements of electron reconstruction, identification, and isolation efficiencies and photon identification efficiencies are presented. They use the full Run 2 data sample collected by the ATLAS experiment in pp collisions at a centre-of-mass energy of 13 TeV during the years 2015–2018, corresponding to an integrated luminosity of 139 fb−1. The measured electron identification efficiencies have uncertainties that are around 30%–50% smaller than the previous Run 2 results due to an improved methodology and the inclusion of more data. A better pile-up subtraction method leads to electron isolation efficiencies that are more independent of the amount of pile-up activity. Updated photon identification efficiencies are also presented, using the full Run 2 data. When compared to the previous measurement, a 30%–40% smaller uncertainty is observed on the photon identification efficiencies, thanks to the increased amount of available data

Performance of the ATLAS forward proton Time-of-Flight detector in Run 2

We present performance studies of the Time-of-Flight (ToF) subdetector of the ATLAS Forward Proton (AFP) detector at the LHC. Efficiencies and resolutions are measured using high-statistics data samples collected at low and moderate pile-up in 2017, the first year when the detectors were installed on both sides of the interaction region. While low efficiencies are observed, of the order of a few percent, the resolutions of the two ToF detectors measured individually are 21 ps and 28 ps, yielding an expected resolution of the longitudinal position of the interaction, z vtx, in the central ATLAS detector of 5.3 ± 0.6 mm. This is in agreement with the observed width of the distribution of the difference between z vtx, measured independently by the central ATLAS tracker and by the ToF detector, of 6.0 ± 2.0 mm

Test of CP-invariance of the Higgs boson in vector-boson fusion production and in its decay into four leptons

A search for CP violation in the decay kinematics and vector-boson fusion production of the Higgs boson is performed in the H → ZZ* → 4ℓ (ℓ = e, μ) decay channel. The results are based on proton-proton collision data produced at the LHC at a centre-of-mass energy of 13 TeV and recorded by the ATLAS detector from 2015 to 2018, corresponding to an integrated luminosity of 139 fb−1. Matrix element-based optimal observables are used to constrain CP-odd couplings beyond the Standard Model in the framework of Standard Model effective field theory expressed in the Warsaw and Higgs bases. Differential fiducial cross-section measurements of the optimal observables are also performed, and a new fiducial cross-section measurement for vector-boson-fusion production is provided. All measurements are in agreement with the Standard Model prediction of a CP-even Higgs boson

Search for pair production of squarks or gluinos decaying via sleptons or weak bosons in final states with two same-sign or three leptons with the ATLAS detector

A search for pair production of squarks or gluinos decaying via sleptons or weak bosons is reported. The search targets a final state with exactly two leptons with same-sign electric charge or at least three leptons without any charge requirement. The analysed data set corresponds to an integrated luminosity of 139 fb−1 of proton-proton collisions collected at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Multiple signal regions are defined, targeting several SUSY simplified models yielding the desired final states. A single control region is used to constrain the normalisation of the WZ + jets background. No significant excess of events over the Standard Model expectation is observed. The results are interpreted in the context of several supersymmetric models featuring R-parity conservation or R-parity violation, yielding exclusion limits surpassing those from previous searches. In models considering gluino (squark) pair production, gluino (squark) masses up to 2.2 (1.7) TeV are excluded at 95% confidence level

A precise measurement of the Z -boson double-differential transverse momentum and rapidity distributions in the full phase space of the decay leptons with the ATLAS experiment at s = 8 TeV

This paper presents for the first time a precise measurement of the production properties of the Z boson in the full phase space of the decay leptons. This is in contrast to the many previous precise unfolded measurements performed in the fiducial phase space of the decay leptons. The measurement is obtained from proton–proton collision data collected by the ATLAS experiment in 2012 at s=8 TeV at the LHC and corresponding to an integrated luminosity of 20.2 fb-1. The results, based on a total of 15.3 million Z-boson decays to electron and muon pairs, extend and improve a previous measurement of the full set of angular coefficients describing Z-boson decay. The double-differential cross-section distributions in Z-boson transverse momentum pT and rapidity y are measured in the pole region, defined as 8