High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance

It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3 years of follow-up. Bone marrow (BM) MRD analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36 months of maintenance therapy. Thirty-seven patients (44%) did not have detectable residual disease in the BM prior to maintenance therapy. Interestingly, 29 patients with detectable residual disease in the BM after induction no longer had detectable disease in the BM following maintenance therapy. After a median followup of 6.30 years, the median overall survival (OS) and PFS had not been reached in patients with either undetectable or detectable residual disease in the BM, who had achieved a complete response at the time of starting maintenance therapy. Interestingly, univariate analysis showed that after rituximab maintenance OS was not affected by IGHV status (mutated vs. unmutated OS: 85.7% alive at 7.2 years vs. 79.6% alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and BM residual disease after four courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete two additional courses of rituximab and continue with maintenance therapy for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full six cycles of the induction regimen. These data show that, compared to historic controls, patients treated with FCR followed by rituximab maintenance have high-quality responses with fewer relapses and improved OS. The tolerability of this regime is favorable. Furthermore, attaining an early undetectable residual disease status could shorten the duration of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of BM MRD after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with CLL undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies

Search for dark matter produced in association with heavy-flavor quark pairs in proton-proton collisions at √s=13TeV

A search is presented for an excess of events with heavy-flavor quark pairs (tt¯ and bb¯) and a large imbalance in transverse momentum in data from proton–proton collisions at a center-of-mass energy of 13TeV. The data correspond to an integrated luminosity of 2.2fb-1 collected with the CMS detector at the CERN LHC. No deviations are observed with respect to standard model predictions. The results are used in the first interpretation of dark matter production in tt¯ and bb¯ final states in a simplified model. This analysis is also the first to perform a statistical combination of searches for dark matter produced with different heavy-flavor final states. The combination provides exclusions that are stronger than those achieved with individual heavy-flavor final states. © 2017, CERN for the benefit of the CMS collaboration

Measurement of differential cross sections for Z boson production in association with jets in proton-proton collisions at √s=13TeV

The production of a Z boson, decaying to two charged leptons, in association with jets in proton-proton collisions at a centre-of-mass energy of 13TeV is measured. Data recorded with the CMS detector at the LHC are used that correspond to an integrated luminosity of 2.19fb-1. The cross section is measured as a function of the jet multiplicity and its dependence on the transverse momentum of the Z boson, the jet kinematic variables (transverse momentum and rapidity), the scalar sum of the jet momenta, which quantifies the hadronic activity, and the balance in transverse momentum between the reconstructed jet recoil and the Z boson. The measurements are compared with predictions from four different calculations. The first two merge matrix elements with different parton multiplicities in the final state and parton showering, one of which includes one-loop corrections. The third is a fixed-order calculation with next-to-next-to-leading order accuracy for the process with a Z boson and one parton in the final state. The fourth combines the fully differential next-to-next-to-leading order calculation of the process with no parton in the final state with next-to-next-to-leading logarithm resummation and parton showering. © 2018, CERN for the benefit of the CMS collaboration

Measurements of the associated production of a Z boson and b jets in pp collisions at √s=8TeV

Measurements of the associated production of a Z boson with at least one jet originating from a b quark in proton–proton collisions at s=8TeV are presented. Differential cross sections are measured with data collected by the CMS experiment corresponding to an integrated luminosity of 19.8fb-1. Z bosons are reconstructed through their decays to electrons and muons. Cross sections are measured as a function of observables characterizing the kinematics of the b jet and the Z boson. Ratios of differential cross sections for the associated production with at least one b jet to the associated production with any jet are also presented. The production of a Z boson with at least two b jets is investigated, and differential cross sections are measured for the dijet system. Results are compared to theoretical predictions, testing two different flavour schemes for the choice of initial-state partons. © 2017, CERN for the benefit of the CMS collaboration

Measurements with silicon photomultipliers of dose-rate effects in the radiation damage of plastic scintillator tiles in the CMS hadron endcap calorimeter

Measurements are presented of the reduction of signal output due to radiation damage for two types of plastic scintillator tiles used in the hadron endcap (HE) calorimeter of the CMS detector. The tiles were exposed to particles produced in proton-proton (pp) collisions at the CERN LHC with a center-of-mass energy of 13 TeV, corresponding to a delivered luminosity of 50 fb-1. The measurements are based on readout channels of the HE that were instrumented with silicon photomultipliers, and are derived using data from several sources: A laser calibration system, a movable radioactive source, as well as hadrons and muons produced in pp collisions. Results from several irradiation campaigns using 60Co sources are also discussed. The damage is presented as a function of dose rate. Within the range of these measurements, for a fixed dose the damage increases with decreasing dose rate

Azimuthal separation in nearly back-to-back jet topologies in inclusive 2- and 3-jet events in pp collisions at √s=13Te

A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Δϕ12, is presented. The measurement considers events where the two leading jets are nearly collinear (“back-to-back”) in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13Te and corresponding to an integrated luminosity of 35.9fb-1 are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with the measurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 ∘< Δϕ12< 180 ∘. The 2- and 3-jet measurements are not simultaneously described by any of models. © 2019, CERN for the benefit of the CMS collaboration